WO2010041964A1

WO2010041964A1 - Methods for the preparation of alkenylamines, cyclic carbamates or dithiocarbamates, and aminoalcohols or aminothiols

Info

Publication number: WO2010041964A1
Application number: PCT/NZ2009/000216
Authority: WO
Inventors: Emma M. Dangerfield; Bridget L. Stocker; Mattheus S. M. Timmer
Original assignee: Victoria Link Limited
Priority date: 2008-10-09
Filing date: 2009-10-09
Publication date: 2010-04-15

Abstract

A method for preparing an alkenylamine, or a salt, solvate or hydrate thereof, is disclosed. The method comprises reacting a alogen-substituted cyclic acetal or a derivative thereof under particular conditions to provide the alkenylamine, which may be optionally converted into a salt, solvate or hydrate thereof. A method for preparing a cyclic carbamate or cyclic dithiocarbamate, or a salt, solvate or hydrate thereof, is also disclosed. The method comprises reacting an alkenylamine under particular conditions to provide the cyclic carbamate or cyclic dithiocarbamate, which may be optionally converted into a salt, solvate or hydrate thereof. A method for preparing a 1,2-aminoalcohol or 1,2-aminothiol, or a salt, solvate or hydrate thereof, is also disclosed. The method comprises forming a cyclic carbamate or cyclic dithiocarbamate from an alkenylamine, and deprotecting the cyclic carbamate or cyclic dithiocarbamate to provide the 1,2-aminoalcohol or 1,2-aminothiol, which may optionally be converted into a salt, solvate or hydrate thereof.

Description

Methods for the preparation of alkenylamines, cyclic carbamates or dithiocarbamates, and aminoalcohols or aminothiols

TECHNICAL FIELD

The present invention relates to methods for preparing alkenylamines from cyclic acetals or derivatives thereof, methods for preparing cyclic carbamates and cyclic dithiocarbamates from alkenylamines, and methods for preparing aminoalcohols and aminothiols from cyclic carbamates and cyclic dithiocarbamates, respectively. More particularly, the present invention relates to regio- and stereo-selective methods for preparing these compounds.

BACKGROUND ART

Owing to their properties as inhibitors of glycosidases, polyhydroxylated alkaloids have enormous therapeutic potential in diseases such as viral infection, bacterial infection, lysosomal storage disorders, cancer and diabetes. The nature of the glycosidases that will be inhibited by certain imino-sugars may, to some extent, be predicted from the number, position and configuration of the substituents. However, there can be marked differences in the inhibition of isoenzymes of a given glycosidase in different species and even within the same cell. Many tumour cells display aberrant glycosylation due to an altered expression of glycosyltransferases and levels of glycosidases are elevated in the sera of many patients with tumours. However, due largely to the limited availability of the imino-sugars, only a few (principally 1-deoxynojirimycin (DNJ), 1-deoxymannojirimycin (DMJ), castanospermine and.swainsonine) have been widely studied for their therapeutic potential.

1 -Deoxynojirimycin 1 -Deoxymannojirimycin (DNJ) (DMJ)

Castanospermine Swainsonine

Five-membered imino-sugars, also known as hydroxypyrrolidines, include: the α-galactosidase inhibitor l,4-dideoxy-l,4-imino-D-lyxitol (A); the mannosidase inhibitors l,4-dideoxy-l,4- imino-D-mannitol (B) and l,4,6-trideoxy-l,4-imino-D-mannitol (C); l,4-dideoxy-l,4-imino-D- xylitol (D); l,4-dideoxy-l,4-imino-L-lyxitol (E); swainsonine, which inhibits both lysosomal α- mannosidase and monosidase II; the potent inhibitor of β-galactosidase and α-mannosidase, broussonetinine A (F); gualamycin (G); and the antibiotic anisomycin (H).

D-lyxo B R = CH₂OH D D-xy/o E L-lyxo C R = CH₃

G Gualamycin H Anisomycin

Many strategies for the synthesis of hydroxypyrrolidines have been reported (see, for example, La Fera, B.; Nicotra, F. "Synthetic Methods for the Preparation of Iminosugars", Ch. 4, in Iminosugars as Glycosidase Inhibitors: Nojirimycin and Beyond (1999), p. 68-92, Arnold E. Stϋtz, (Ed.), Weinheim Germany: Wiley- VC Y). Many of these strategies are lengthy, some show poor diastereoselectivity, and all employ standard protecting group manipulations. The extensive use of protecting groups has many disadvantages including the use of organic solvents for reactions, work-up, and purification, and may be environmentally deleterious. In addition, extensive protecting group manipulations lead to lengthy syntheses requiring both a protection and deprotection step per protecting group, resulting in reduced atom economy and hence, reaction efficiency.

Accordingly, it is an object of the present invention to go some way to avoiding the above disadvantages or to at least provide the public with a useful choice.

Other objects of the invention may become apparent from the following description which is given by way of example only. Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is solely for the purpose of providing a context for the present invention. It is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the present invention as it existed before the priority date.

SUMMARY OF THE INVENTION

In a first aspect, the present invention provides a method for preparing an alkenylamine, or a salt, solvate or hydrate thereof, the method comprising: reacting a halogen-substituted cyclic acetal or a derivative thereof with a reaction metal, a source of ammonia and a hydride source to provide the alkenylamine; optionally converting the alkenylamine into a salt, solvate or hydrate thereof; and optionally isolating the alkenylamine or salt, solvate or hydrate thereof.

In a second aspect, the present invention provides a method for preparing a cyclic carbamate or cyclic dithiocarbamate, or a salt, solvate or hydrate thereof, the method comprising: reacting an alkenylamine with a halogen source, a base and a source of carbonate or a source of carbon dioxide or a source of carbon disulfide to provide the cyclic carbamate or cyclic dithiocarbamate; optionally converting the cyclic carbamate or cyclic dithiocarbamate into a salt, solvate or hydrate thereof; and optionally isolating the cyclic carbamate or cyclic dithiocarbamate or salt, solvate or hydrate thereof.

In a third aspect the present invention provides a method for preparing a cyclic carbamate or cyclic dithiocarbamate, or a salt, solvate or hydrate thereof, the method comprising: reacting a halogen-substituted cyclic acetal or a derivative thereof with a reaction metal, a source of ammonia and a hydride source to provide an alkenylamine; reacting the alkenylamine with a halogen source, a base and a source of carbonate or a source of carbon dioxide or a source of carbon disulfide to provide the cyclic carbamate or cyclic dithiocarbamate; optionally converting the cyclic carbamate or cyclic dithiocarbamate into a salt, solvate or hydrate thereof; and optionally isolating the cyclic carbamate or cyclic dithiocarbamate or salt, solvate or hydrate thereof.

In a fourth aspect, the present invention provides a method for preparing a 1,2-aminoalcohol or 1,2-aminothiol, or a salt, solvate or hydrate thereof, the method comprising: reacting an alkenylamine with a halogen source, a base and a source of carbonate or a source of carbon dioxide or a source of carbon disulfide to provide a cyclic carbamate or cyclic dithiocarbamate; deprotecting the cyclic carbamate or cyclic dithiocarbamate to provide the 1,2-aminoalcohol or 1,2-aminothiol; optionally converting the 1,2-aminoalcohol or 1,2-aminothiol into a salt, solvate or hydrate thereof; and optionally isolating the 1 ,2-aminoalcohol or 1 ,2-aminothiol or salt, solvate or hydrate thereof.

In a fifth aspect, the present invention provides a method for preparing a 1,2-aminoalcohol or

1,2-aminothiol, or a salt, solvate or hydrate thereof, the method comprising: reacting a halogen-substituted cyclic acetal or a derivative thereof with a reaction metal, a source of ammonia and a hydride source to provide an alkenylamine; reacting the alkenylamine with a halogen source, a base and a source of carbonate or a source of carbon dioxide or a source of carbon disulfide to provide a cyclic carbamate or cyclic dithiocarbamate; deprotecting the cyclic carbamate or cyclic dithiocarbamate to provide the 1,2-aminoalcohol or

1,2-aminothiol; optionally converting the 1,2-aminoalcohol or 1,2-aminothiol into a salt, solvate or hydrate thereof; and optionally isolating the 1,2-aminoalcohol or 1,2-aminothiol or salt, solvate or hydrate thereof.

The invention also provides an alkenylamine, or a salt, solvate or hydrate thereof, when prepared by a method of the invention.

The invention also provides a cyclic carbamate, or a salt, solvate or hydrate thereof, when prepared by a method of the invention.

The invention also provides a cyclic dithiocarbamate, or a salt, solvate or hydrate thereof, when prepared by a method of the invention. The invention also provides a 1,2-aminoalcohol, or a salt, solvate or hydrate thereof, when prepared by a method of the invention.

The invention also provides a 1,2-aminothiol, or a salt, solvate or hydrate thereof, when prepared by a method of the invention.

The invention also provides the halogen-substituted cyclic acetal:

The invention also provides an alkenylamine selected from the group consisting of:

The invention also provides a cyclic carbamate selected from the group consisting of:

This invention may also be said broadly to consist in the parts, elements and features referred to or indicated in the specification of the application, individually or collectively, and any or all combinations of any two or more said parts, elements or features, and where specific integers are mentioned herein which have known equivalents in the art to which this invention relates, such known equivalents are deemed to be incorporated herein as if individually set forth.

As used herein, the term "salt" is intended to include acid addition salts of any basic moiety that may be present in a compound useful in the invention, and base addition salts of any acidic moiety that may be present in a compound useful in the invention. Such salts are generally prepared by reacting the compound with a suitable organic or inorganic acid or base. Examples of salts of basic moieties include: sulfates; methanesulfonates; acetates; hydrochlorides; hydrobromides; phosphates; toluenesulfonates; citrates; maleates; succinates; tartrates; lactates; and fumarates. Examples of salts of acidic moieties include: ammonium salts; alkali metal salts such as sodium salts and potassium salts; and alkaline earth metal salts such as calcium salts and magnesium salts. Other salts will be apparent to those skilled in the art.

The compounds useful in the invention, and their salts or other derivatives, may form hydrates, or solvates with various solvents. The present invention contemplates such hydrates and solvates as well as the corresponding unsolvated forms.

The compounds useful in the invention may have asymmetric carbon atoms. Therefore, stereoisomers (both enantiomers and diastereomers) of such compounds can exist. The present invention contemplates the pure stereoisomers and any mixture of the isomers. For example, a pure enantiomer of a compound can be isolated from a mixture of enantiomers of the compound using conventional optical resolution techniques. Enol forms and tautomers are also contemplated, where appropriate.

The invention also contemplates "radiolabeled compounds", which are compounds that contain unnatural proportions of atomic isotopes. Such compounds may be useful as therapeutic, diagnostic or research reagents.

The general chemical terms used in the formulae herein have their usual meanings.

For example, as used herein:

the term "alkyl" is intended to include straight chain and branched chain saturated hydrocarbon groups. In one embodiment, alkyl groups comprise 1 to 30 carbon atoms. In a preferred embodiment, alkyl groups comprise the aliphatic chain of a short chain, medium chain or long chain fatty acid. In another preferred embodiment, alkyl groups comprise 1 to 6 carbon atoms. In another preferred embodiment, the alkyl group is methyl, ethyl, n-propyl, i-propyl, n-butyl, i- butyl or t-butyl;

the term "cycloalkyr' is intended to include cyclic saturated hydrocarbon groups;

the term "alkenyl" is intended to include straight chain and branched chain unsaturated hydrocarbon groups; the term "cycloalkenyl" is intended to include cyclic unsaturated hydrocarbon groups;

the term ""alkynyl" is intended to include straight chain and branched chain hydrocarbon groups including a carbon-carbon triple bond;

the term "alkoxy" is intended to include alkyl-O- groups;

the term "cycloalkoxy" is intended to include cycloalkyl-O- groups;

the term "aryl" is intended to include aromatic radicals including, but not limited to: phenyl; naphthyl; indanyl; biphenyl; and the like. In one embodiment, preferred aryl groups comprise 4 to 10 ring carbon atoms;

the term "amino" is intended to include -NH₂ groups wherein one or both of the hydrogen atoms may be replaced, independently, by an optionally substituted alkyl or aryl group;

the term "amido" is intended to include amino-C(O)- groups;

the term "imino" is intended to include =NH groups, wherein the hydrogen atom may be replaced by an optionally substituted alkyl or aryl group;

the term "aryloxy" is intended to include aryl-O- groups;

the term "heteroaryl" is intended to include heteroaromatic radicals including, but not limited to: pyrimidinyl; pyridyl; pyrrolyl; furyl; oxazolyl; thiophenyl; and the like;

the term "heteroaryloxy" is intended to include heteroaryl-O- groups;

the term "heterocyclyl" is intended to include non-aromatic heterocyclic radicals including, but not limited to: piperidinyl; pyrrolidinyl; piperazinyl; 1,4-dioxanyl; tetrahydrofuranyl; tetrahydrothiophenyl; and the like;

the term "heterocyclyloxy" is intended to include heterocyclyl-O- groups;

the term "acyl" is intended to include -C(O)R groups, wherein R is an optionally substituted alkyl or aryl group;

the term "carboxyl" is intended to include -C(O)OH groups, wherein the hydrogen atom may be replaced by an optionally substituted alkyl or aryl group or a cation; the term "halo" is intended to mean chloro, bromo, fluoro, or iodo;

the term "metal" is intended to include, but is not limited to: lithium; sodium; potassium; magnesium; calcium; aluminium; manganese; nickel; copper; zinc; and tin;

the term "oxy" is intended to mean the -O- group;

the term "borane" is intended to include -BH₂ groups wherein one or both of the hydrogen atoms may be replaced, independently, by an optionally substituted alkyl or aryl group;

the term "boronic" is intended to include -B(OH)₂ groups wherein one or both of the hydrogen atoms may be replaced, independently, by an optionally substituted alkyl or aryl group or a metal;

the term "phosphate" is intended to include -OP(O)(OH)₂ groups wherein one or both of the hydrogen atoms may be replaced, independently, by an optionally substituted alkyl or aryl group or a metal;

the term "phosphinate" is intended to include -OP(O)H₂ and -P(O)(OH)H groups wherein one or both of the hydrogen atoms may be replaced, independently, by an optionally substituted alkyl or aryl group or a metal;

the term "phosphine" is intended to include -PH₂ groups wherein one or both of the hydrogen atoms may be replaced, independently, by an optionally substituted alkyl or aryl group;

the term "phosphite" is intended to include -OP(OH)₂ groups wherein one or both of the - hydrogen atoms may be replaced, independently, by an optionally substituted alkyl or aryl group or a metal;

the term "phosphonate" is intended to include -P(O)(OH)₂ and -OP(O)(OH)H groups wherein one or both of the hydrogen atoms may be replaced, independently, by an optionally substituted alkyl or aryl group or a metal;

the term "silane" is intended to include -SiH₃ groups, wherein one, two or all three of the hydrogen atoms may be replaced, independently, by an optionally substituted alkyl or aryl group;

the term "siloxane" is intended to include -Si(O)H groups, where the hydrogen atom may be replaced by an optionally substituted alkyl or aryl group or a metal; the term "sulfate" is intended to include -OS(O)₃H groups, wherein the hydrogen atom may be replaced by an optionally substituted alkyl or aryl group or a metal;

the term "sulfenyl" is intended to include -SR groups, wherein R is an optionally substituted alkyl or aryl group;

the term "sulfonyl" is intended to include -S(O)₂R groups, wherein R is an optionally substituted alkyl or aryl group; and

the term "sulfoxide" is intended to include -S(O)R groups, wherein R is an optionally substituted alkyl or aryl group.

As used herein, the term "substituted" is intended to mean that one or more hydrogen atoms in the group indicated is replaced with one or more independently selected suitable substituents, provided that the normal valency of each atom to which the substituent/s are attached is not exceeded, and that the substitution results in a stable compound.

Unless a moiety of a compound is defined as being unsubstituted, that moiety may be substituted. In a preferred embodiment, the substituents are independently selected from the group consisting of alkyl, cycloalkyl, cycloalkyloxy, alkenyl, cycloalkenyl, alkoxy, aryl, aryloxy, heterocyclyl, heterocyclyloxy, heteroaryl, heteroaryloxy, acyl, carboxyl, amino, amido, imino, -NO₂, -NO, -CN, -N₃, -OH, sulfenyl, sulfonyl, sulfoxide, sulfate, phosphate, phosphonate, phosphinate, phosphine, phosphite and halo.

The term "substituted sulfur" is intended to include sulfate, sulfenyl, sulfonyl and sulfoxide groups.

The term "substituted silicon" is intended to include silane and siloxane groups.

The term "substituted boron" is intended to include borane and boronic groups.

The term "substituted phosphorus" is intended to include phosphate, phosphinate, phosphine, phosphite and phosphonate groups.

The term "comprising" as used in this specification means "consisting at least in part of. When interpreting each statement in this specification that includes the term ""comprising", features other than that or those prefaced by the term may also be present. Related terms such as "comprise" and "comprises" are to be interpreted in the same manner. It is intended that reference to a range of numbers disclosed herein (for example, 1 to 10) also incorporates reference to all rational numbers within that range (for example, 1, 1.1, 2, 3, 3.9, 4, 5, 6, 6.5, 7, 8, 9 and 10) and also any range of rational numbers within that range (for example, 2 to 8, 1.5 to 5.5 and 3.1 to 4.7) and, therefore, all sub-ranges of all ranges expressly disclosed herein are hereby expressly disclosed. These are only examples of what is specifically intended and all possible combinations of numerical values between the lowest value and the highest value enumerated are to be considered to be expressly stated in this application in a similar manner.

Although the present invention is broadly as defined above, those persons skilled in the art will appreciate that the invention is not limited thereto and that the invention also includes embodiments of which the following description gives examples.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to a two-stage synthesis of 1,2-aminoalcohols or 1,2-aminothiols, in which a key step is the formation of a cyclic carbamate or cyclic dithiocarbamate from a precursor alkenylamine. The alkenylamines, in turn, are accessible in one step from halogenated cyclic acetals or derivatives thereof. As such, the methods of the present invention provide facile access to compounds for use in myriad applications, whether as synthetic intermediates, pharmaceutical compounds or chiral ligands for asymmetric synthesis.

One embodiment of the various aspects of the invention is illustrated in the following scheme.

II I III IV

SCHEME I

Scheme I illustrates the preparation of an alkenylamine of Formula I from a halogen-substituted cyclic acetal or a derivative thereof of Formula II. The alkenylamine may be reacted to form a cyclic carbamate (Y=O) or cyclic dithiocarbamate (Y=S) of Formula III, which may be deprotected to form a 1 ,2-aminoalcohol (Y=O) or 1 ,2-aminothiol (Y=S) of Formula IV.

Preferably, Y is O. Preferred halogen-substituted cyclic acetals include an alkoxy, substituted alkoxy, alkenyloxy or aryloxy leaving group, more preferably an alkoxy leaving group.

Preferred halogen-substituted cyclic acetals and derivatives thereof include a leaving group selected from the group consisting of halogen, -OR¹⁰, -NHR¹⁰, -N(R¹⁰)₂, -SR¹⁰, -SOR¹⁰, -SO₂R¹⁰ and -SeR¹⁰, wherein R¹⁰ is independently selected from -H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkoxy, substituted alkoxy, acyl, substituted acyl, acetimidoyl, substituted acetimidoyl, amino, substituted amino and halogen.

Accordingly, in a first aspect, the present invention provides a method for preparing an alkenylamine, or a salt, solvate or hydrate thereof, the method comprising: reacting a halogen-substituted cyclic acetal or a derivative thereof with a reaction metal, a source of ammonia and a hydride source to provide the alkenylamine; optionally converting the alkenylamine into a salt, solvate or hydrate thereof; and optionally isolating the alkenylamine or salt, solvate or hydrate thereof.

In a preferred embodiment, the halogen-substituted cyclic acetal or derivative thereof is enantiopure and the reaction is stereo- and regioselective, such that the resulting alkenylamine is chiral.

In another preferred embodiment, the halogen-substituted cyclic acetal or derivative thereof is stereoisomerically pure and the reaction is stereo- and regioselective, such that the resulting alkenylamine is stereoisomerically pure.

One embodiment of the first aspect of the invention is a method -for preparing a compound of Formula I:

or a salt, solvate or hydrate thereof; wherein L is selected from the group consisting of:

-C(Rⁿ)(R¹²)C(R²¹)(R²²)C(R³¹)(R³²)C(R⁴¹)(R⁴²)C(R⁵¹)(R⁵²)-; -C(Rⁿ)(R¹²)C(R²¹)(R²²)C(R³¹)(R³²)C(R⁴¹)(R⁴²)-; -C(R¹¹)(R¹²)C(R²¹)(R²²)C(R³¹)(R³²)-; and -C(R¹¹XR^)C(R²¹XR²²)-; wherein R¹¹, R¹², R²¹, R²², R³¹, R³², R⁴¹, R⁴², R⁵¹ and R⁵² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; or R¹¹ and R¹², R²¹ and R²², R³¹ and R³², R⁴¹ and R⁴², and/or R⁵¹ and R⁵², together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or R¹¹ and R²¹, R¹² and R²², R²¹ and R³¹, R²² and R³², R³¹ and R⁴¹, R³² and R⁴², R⁴¹ and R⁵¹, and/or R⁴² and R⁵², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl; or R¹¹ and R¹², R²¹ and R²², R³¹ and R³², R⁴¹ and R⁴², and/or R⁵¹ and R⁵² together form a =C(R⁵)₂, =CR⁶(XR⁷), or =C(XR⁷)₂ group; wherein R¹, R², R³, R⁴, R⁵, R⁶ and R⁷ at each occurrence are independently selected from -H, -CN, -R⁸, -C(X)R⁸, -C(X)XR⁸, -C(R⁸)₃, -C(R⁸)₂XR⁸, -CR⁸(XR⁸)₂ and -C(XR⁸)₃; wherein X at each occurrence is independently selected from O, NH, NR and S; and R⁸ and R⁹ at each occurrence are independently selected from -H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, sulfur, substituted sulfur, silicon, substituted silicon, boron, substituted boron, phosphorus, substituted phosphorus and metal; or R³ and R⁴ together form a =C(R⁵)₂ , =CR⁶(XR⁷), or =C(XR⁷)₂ group; the method comprising: reacting a compound of Formula II:

wherein Z is halo, A is a leaving group, and L is as defined for Formula I; with a reaction metal, a source of ammonia and a hydride source to provide the compound of Formula I; optionally converting the compound of Formula I into a salt, solvate or hydrate thereof; and optionally isolating the compound of Formula I or salt, solvate or hydrate thereof. In a preferred embodiment, the compound of Formula II is selected from the group consisting of the compounds of Formula Ha, lib and Hc:

In a further preferred embodiment, the compound of Formula II is selected from the group consisting of the compounds of Formula Ha and lib.

In a preferred embodiment, the compound of Formula I is selected from the group consisting of the compounds of Formula Ia₅ Ib and Ic:

_R1i f T² R¹¹J ¹² tW

Il R21 Ia I R²¹ R²² NH₂ Ib

_IC.

In a further preferred embodiment, the compound of Formula I is selected from the group consisting of the compounds of Formula Ia and Ib.

In another preferred embodiment, the compound of Formula I has the Formula Ia:

wherein R¹¹, R¹², R²¹ and R²² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; wherein R¹, R², R³ and R⁴ are as defined for Formula I;

1 1 I O O I OO or R and R and/or R and R , together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or R¹¹ and R²¹ and/or R¹² and R²², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

In another preferred embodiment, the compound of Formula I has the Formula Ia; wherein R 11 and R" are -H, and R¹² and R are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; wherein R¹, R², R³ and R⁴ are as defined for Formula I; or R¹² and R²², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

In another preferred embodiment, the compound of Formula I has the Formula Ia; wherein R¹¹ and R²¹ are -H, and R¹² and R²² are each independently selected from the group consisting of -H, -N₃, -OR² and -NR³R , wherein R², R³ and R⁴ at each occurrence are each independently selected from -H, -R⁸, -C(X)R⁸ and -C(X)XR⁸; X at each occurrence is independently selected from O, NH, NR and S; and

R⁸ and R⁹ at each occurrence are independently selected from -H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxide, substituted alkoxide, sulfur, substituted sulfur, silicon, substituted silicon, boron, substituted boron, phosphorus, substituted phosphorus and metal.

In another preferred embodiment, the compound of Formula I has the Formula Ia; wherein R¹¹ and R²¹ are -H, R¹² is -OH; and R²² is selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; wherein R¹, R², R³ and R⁴ are as defined for Formula I.

In another preferred embodiment, the compound of Formula I has the Formula Ia; wherein R π and R²¹ are -H, and R¹² and R²² are -OH.

In another preferred embodiment, the compound of Formula I has the Formula Ia; wherein R , R²¹ and R²² are -H, and R¹² is -OH.

In another preferred embodiment, the compound of Formula I has the Formula Ib:

wherein

R¹¹, R¹², R²¹, R²², R³¹ and R³² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; wherein R¹, R², R³ and R⁴ are as defined for Formula I; or R¹¹ and R¹², R²¹ and R²², and/or R³¹ and R³², together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or R¹¹ and R²¹, R¹² and R²², R²¹ and R³¹, and/or R²² and R³², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

In another preferred embodiment, the compound of Formula I has the Formula Ib; wherein R , R and R are -H, and R , R and R are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; wherein R¹, R², R³ and R⁴ are as defined for Formula I; or R and R and/or R and R together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

In another preferred embodiment, the compound of Formula I has the Formula Ib; wherein R¹¹, R²¹ and R³¹ are -H, and R¹², R²² and R³² are each independently selected from the group consisting of -H, -N₃, -OR² and -NR³R , wherein R², R³ and R at each occurrence are each independently selected from -H, -R⁸, -C(X)R⁸ and -C(X)XR⁸; X at each occurrence is independently selected from O, NH, NR⁹ and S; and

R and R at each occurrence are independently selected from -H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxide, substituted alkoxide, sulfur, substituted sulfur, silicon, substituted silicon, boron, substituted boron, phosphorus, substituted phosphorus and metal.

In another preferred embodiment, the compound of Formula I has the Formula Ib; wherein R¹¹, R²¹ and R³¹ are -H; R¹² is -OH; and

R²² and R³² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; wherein R¹, R², R³ and R⁴ are as defined for Formula I. In another preferred embodiment, the compound of Formula I has the Formula Ib; wherein R¹¹, R²¹ and R³¹ are -H; R¹² and R²² are -OH; and

R³² is selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; wherein R¹, R², R³ and R⁴ are as defined for Formula I.

In another preferred embodiment, the compound of Formula I has the Formula Ib; wherein R¹¹, R²¹ and R³¹ are -H, and R¹², R²² and R³² are -OH.

In another preferred embodiment, the compound of Formula I has the Formula Ib; wherein R ^l, R²¹, R³¹ and R³² are -H, and R¹² and R²² are -OH.

In another preferred embodiment, the compound of Formula I has the Formula Ic:

wherein

R¹¹, R¹², R²¹, R²², R³¹, R³², R⁴¹and R⁴² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; wherein R¹, R², R³ and R⁴ are as defined for Formula I; or R¹¹ and R¹², R²¹ and R²², R³¹ and R³², and/or R⁴¹ and R⁴², together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cyeloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or R¹¹ and R²¹, R¹² and R²², R²¹ and R³¹, R²² and R³², R³¹ and R⁴¹, and/or R³² and R⁴², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

In another preferred embodiment, the compound of Formula I has the Formula Ic; wherein R¹¹, R²¹, R³¹ and R⁴¹ are -H, and R¹², R²², R³² and R⁴² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; wherein R¹, R², R³ and R⁴ are as defined for Formula I; or R¹² and R²², R²² and R³², and/or R³² and R⁴², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

In another preferred embodiment, the compound of Formula I has the Formula Ic; wherein R¹¹, R²¹, R³¹ and R⁴¹ are -H, and R¹², R²², R³² and R⁴² are each independently selected from the group consisting of -H, -N₃, -OR² and -NR³R⁴, wherein R², R³ and R⁴ at each occurrence are each independently selected from -H, -R⁸, -C(X)R⁸ and -C(X)XR⁸; X at each occurrence is independently selected from O, NH, NR⁹ and S; and R⁸ and R⁹ at each occurrence are independently selected from -H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxide, substituted alkoxide, sulfur, substituted sulfur, silicon, substituted silicon, boron, substituted boron, phosphorus, substituted phosphorus and metal.

In another preferred embodiment, the compound of Formula I has the Formula Ic; wherein R¹¹, R²¹, R³¹ and R⁴¹ are -H; R¹² is -OH; and

R²², R³² and R⁴² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; wherein R¹, R², R³ and R⁴ are as defined for

Formula I.

In another preferred embodiment, the compound of Formula I has the Formula Ic; wherein R¹¹, R²¹, R³¹ and R⁴¹ are -H; R¹² and R²² are -OH; and

R³² and R⁴² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; wherein R¹, R², R³ and R⁴ are as defined for Formula I.

In another preferred embodiment, the compound of Formula I has the Formula Ic; wherein R¹¹, R²¹, R³¹ and R⁴¹ are -H; and R¹², R²², R³² and R⁴² are -OH.

In one embodiment, the leaving group A is selected from the group consisting of halogen, -OR¹⁰, -NHR¹⁰, -N(R¹⁰)₂, -SR¹⁰, -SOR¹⁰, -SO₂R¹⁰ and -SeR¹⁰, wherein R¹⁰ is independently selected from -H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkoxy, substituted alkoxy, acyl, substituted acyl, acetimidoyl, substituted acetimidoyl, amino, substituted amino and halogen.

Preferably, the leaving group A is -OR¹⁰.

In a preferred embodiment, R¹⁰ is alkyl.

In a further preferred embodiment, R¹⁰ is alkyl, substituted alkyl, alkenyl or aryl.

In another preferred embodiment, R¹⁰ is selected from the group consisting of methyl, ethyl, propyl, butyl, allyl, phenyl and benzyl.

In another preferred embodiment, R¹⁰ is methyl.

In one embodiment, Z is selected from the group consisting of -I, -Br and -Cl.

Preferably, Z is -I.

In one embodiment, the reaction metal is selected from the group consisting of lithium, sodium, potassium, zinc, barium, magnesium, titanium, zirconium, indium, and mixtures of any two or more thereof.

In a further embodiment, the reaction metal is an alloy. Preferred alloys include amalgams, such as Zn(Hg) and Na(Hg).

Preferably, the reaction metal is zinc.

In one embodiment, the source of ammonia is NH₃. The NH₃ may be ammonia gas, a solution of ammonia or a mixture thereof. In those embodiments wherein the source of ammonia comprises a solution of ammonia, the solution may be aqueous ammonia or a solution of ammonia in an organic solvent, for example an alcoholic ammonia solution. Preferred alcoholic ammonia solutions comprise a solution of ammonia in methanol or ethanol.

In another embodiment, the source of ammonia is an ammonium salt.

Preferably, the ammonium salt is selected from the group consisting OfNH₄OH, NH₄Cl, NH₄OAc, NH₄HCO₂, NH₄HSO₄, (NH₄)₂SO₄, NH₄HCO₃, (NH₄)₂CO₃, and mixtures of any two or more thereof. More preferably, the ammonium salt is NH₄OAc. The invention also contemplates embodiments in which the source of ammonia is a mixture of NH₃ (for example, gaseous NH₃ and/or a solution ofNH₃) and one or more ammonium salt.

Those persons skilled in the art will be able to select a suitable hydride source without undue experimentation. The hydride source must be sufficiently reactive to achieve the conversion of the halogen-substituted cyclic acetal or derivative thereof to the desired alkenylamine by reducing the intermediate iminium ion, without being so reactive that the intermediate aldehyde moiety is also reduced.

In one embodiment the hydride source is a metal hydride, such as lithium aluminium hydride or diisobutylaluminium hydride.

In another embodiment, the hydride source is a borohydride. Suitable borohydrides include, but are not limited to: NaBH₄, NaBH₃CN, LiBH₃CN, NaBH₃CN-ZnCl₂, NaBH₃CN-Ti(OzPr)₄, NaBH₃CN-Mg(C10₄)₂, (^-Bu)₄NBH₃CN, NaBH(OAc)₃, NaBH₄-NiCl₂, NaBH₄-ZnCl₂, NaBH₄- ZrCl₄, Ti(OrPr)₄-NaBH₄, and NaBH₄-H₂SO₄. Resins (borohydride exchange resin) and clays (NaBH₄ on wet clay) may also be suitable.

Preferably, the borohydride is sodium cyanoborohydride (NaBH₃CN) or sodium triacetoxyborohydride (NaBH(O Ac)₃) .

Advantageously, NaBH₃CN is stable in relatively strong acid solutions (pH 3), and is soluble in hydroxy lie solvents such as methanol. It also has different selectivities at different pH values. At pH 3-4 it reduces aldehydes and ketones effectively, but this reduction becomes very slow at higher pH values. At pH 6-8, the more basic imines are protonated preferentially and reduced faster than aldehydes or ketones.

Alternative hydride sources include the use of Lewis-acid catalysis, with reagents such as NaBH₃CN-ZnCl₂, NaBH₃CN-Ti(OzPr)₄, NaBH₄-ZnCl₂, NaBH₄-ZrCl₄, and Ti(OzPr)₄-NaBH₄. Some of these milder Lewis acids, for example ZnCl₂, may stabilise the hydride reducing agent in aqueous media.

A further alternative hydride source is sodium borohydride activated by boric acid.

Other alternative hydride sources include: nickel boride; Zn(BH₄)₂, Zn(BH₄)₂-ZnCl₂, Zn(BH₄)₂- SiO₂, Zn-AcOH, polymethylhydrosiloxane (PMHS)-Ti(OzPr)₄, PMHS-ZnCl₂, PMHS- BuSn(OCOR)₃, Et₃SiH-CF₃CO₂H, (PhMe₂)SiH-(C₆Fe)₃, Cl₃SiH-DMF, PhSiH₃-Bu₂SnCl₂, n- Bu₃SnH-DMF or HMPA, H-Bu₃SnH-SiO₂ and ^-Bu₂SnIH or W-Bu₂SnClH.

Borane reducing agents, including, but not limited to: pyridine-borane; picoline-borane; diborane-MeOH; and decaborane; are other alternative hydride sources.

The compounds of Formula II may be prepared by, for example: halogen substitution of an alkyl hydroxymethylfuranoside using triphenylphosphine and iodine (Skaanderup, P. R.; Poulsen, C. S.; Hyldtoft, L.; Jørgensen, M. R.; Madsen, R. Synthesis 2002, 12, 1721-1727); halogen substitution of an alkyl (methanesulfonyloxymethyl)furanoside with tetrabutylammonium iodide in benzene (Paquette, L.A.; Pissarnitski, D; Barriault, L. J Org Chem. 1998, 21, 7389-7398); or halogen substitution of an alkyl (pαrα-toluenesulfonyloxymethyl)furanoside with sodium iodide in acetone (Liberek, B. Carbohydr Res. 2005, 340, 2039-47). However, the invention is not limited to compounds of Formula II prepared using this method and other methods of preparing these compounds will be apparent to those persons skilled in the art.

The invention also provides a compound of Formula I₅ or a salt, solvate or hydrate thereof, when prepared by a method of the invention.

In a preferred embodiment, the compound of Formula II is enantiopure and the resulting compound of Formula I is chiral. The compound of Formula II may be resolved into enantiomers using methods known to those persons skilled in the art.

In another preferred embodiment, the compound of Formula II is stereoisomerically pure and the resulting compound of Formula I is stereoisomerically pure.

In a second aspect, the present invention provides method for preparing a cyclic carbamate or cyclic dithiocarbamate, or a salt, solvate or hydrate thereof, the method comprising: reacting an alkenylamine with a halogen source, a base and a source of carbonate or a source of carbon dioxide or a source of carbon disulfide to provide the cyclic carbamate or cyclic dithiocarbamate; optionally converting the cyclic carbamate or cyclic dithiocarbamate into a salt, solvate or hydrate thereof; and optionally isolating the cyclic carbamate or cyclic dithiocarbamate or salt, solvate or hydrate thereof. Advantageously, the method of the invention permits the efficient preparation of a cyclic carbamate or cyclic dithiocarbamate from an alkenylamine, since it provides concomitant installation of nitrogen protection. In addition, because the method does not require a 1,2-aminoalcohol or 1,2-aminothiol starting material, it provides a useful means to stereoselectively prepare these important functional motifs from an alkenylamine using simple reagents.

In a preferred embodiment, the alkenylamine is enantiopure and the reaction is stereo- and regioselective, such that the resulting cyclic carbamate or cyclic dithiocarbamate is chiral.

In another preferred embodiment, the alkenylamine is stereoisomerically pure and the reaction is stereo- and regioselective, such that the resulting cyclic carbamate or cyclic dithiocarbamate is stereoisomerically pure.

One embodiment of the second aspect of the invention is a method for preparing a compound of Formula III:

or a salt, solvate or hydrate thereof; wherein Y is O or S;

L is selected from the group consisting of:

-C(R^π)(R¹²)C(R²¹)(R²²)C(R³¹)(R³²)C(R⁴¹)(R⁴²)C(R⁵¹)(R⁵²)-;

-C(R^U)(R¹²)C(R²¹)(R²²)C(R³¹)(R³²)C(R⁴¹)(R⁴²)-; -C(R^π)(R¹²)C(R²¹)(R²²)C(R³¹)(R³²)-; and

-C(R¹¹XR¹^C(R²¹XR²²)-; wherein R¹¹, R¹², R²¹, R²², R³¹, R³², R⁴¹, R⁴², R⁵¹ and R⁵² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; or R¹¹ and R¹², R²¹ and R²², R³¹ and R³², R⁴¹ and R⁴², and/or R⁵¹ and R⁵², together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or R¹¹ and R²¹, R¹² and R²², R²¹ and R³¹, R²² and R³², R³¹ and R⁴¹, R³² and R⁴², R⁴¹ and R⁵¹, and/or R⁴² and R⁵², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl; or R¹¹ and R¹², R²¹ and R²², R³¹ and R³², R⁴¹ and R⁴², and/or R⁵¹ and R⁵² together form a

=C(R⁵)₂, =CR⁶(XR⁷), or =C(XR⁷)₂ group; wherein R¹, R², R³, R⁴, R⁵, R⁶ and R⁷ at each occurrence are independently selected from -H, -CN, -R⁸, -C(X)R⁸, -C(X)XR⁸, -C(R⁸)₃, -C(R⁸)₂XR⁸, -CR⁸(XR⁸)₂ and -C(XR⁸)₃; wherein X at each occurrence is independently selected from O, NH, NR⁹ and S; and

R⁸ and R⁹ at each occurrence are independently selected from -H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, sulfur, substituted sulfur, silicon, substituted silicon, boron, substituted boron, phosphorus, substituted phosphorus and metal; or R³ and R⁴ together form a =C(R⁵)₂ , =CR⁶(XR⁷), or =C(XR⁷)₂ group; the method comprising: reacting a compound of Formula I, as defined above, with a halogen source, a base and a source of carbonate or a source of carbon dioxide or a source of carbon disulfide to provide the compound of Formula III; optionally converting the compound of Formula III into a salt, solvate or hydrate thereof; and optionally isolating the compound of Formula III or salt, solvate or hydrate thereof.

Preferably, Y is O.

In a preferred embodiment, the compound of Formula III is selected from the group consisting of the compounds of Formula Ilia, IHb and HIc:

In a further preferred embodiment, the compound of Formula III is selected from the group consisting of the compounds of Formula HIa and HIb.

In a another preferred embodiment, the compound of Formula III is selected from the group consisting of the compounds of Formula Ilia', IHb' and HIc':

In another preferred embodiment, the compound of Formula III is selected from the group consisting of the compounds of Formula Ilia' and IHb'.

In another preferred embodiment, the compound of Formula III has the Formula Ilia:

wherein Y is O or S;

R , R , R and R are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; wherein R¹, R², R³ and R⁴ are as defined for

Formula I; or R¹¹ and R¹² and/or R²¹ and R²², together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or R¹¹ and R²¹ and/or R¹² and R²², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

More preferably, Y is O.

In another preferred embodiment, the compound of Formula III has the Formula Ilia; wherein Y is O or S;

R¹¹ and R²¹ are -H, and R¹² and R²² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; wherein R¹, R², R³ and R⁴ are as defined for Formula I; or R¹² and R²², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl. More preferably, Y is O.

R and R are -H, and R and R are each independently selected from the group consisting of -H, -N₃, -OR² and -NR³R⁴, wherein R², R³ and R⁴ at each occurrence are each independently selected from -H, -R⁸, -C(X)R⁸ and -C(X)XR⁸;

X at each occurrence is independently selected from O, NH, NR⁹ and S; and R and R at each occurrence are independently selected from -H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxide, substituted alkoxide, sulfur, substituted sulfur, silicon, substituted silicon, boron, substituted boron, phosphorus, substituted phosphorus and metal.

More preferably, Y is O.

R¹¹ and R²¹ are -H;

R¹² is -OH; and

R²² is selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; wherein

R¹, R², R³ and R⁴ are as defined for Formula I.

More preferably, Y is O.

R¹¹ and R²¹ are -H; and

R¹² and R²² are -OH.

More preferably, Y is O.

R¹¹, R^2! and R²² are -H; and

R¹² is -OH. More preferably, Y is O.

In another preferred embodiment, the compound of Formula III has the Formula Mb:

wherein Y is O or S; R¹¹, R¹², R²¹, R²², R³¹ and R³² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; wherein R¹, R², R³ and R⁴ are as defined for Formula I; or R¹¹ and R¹², R²¹ and R²², and/or R³¹ and R³², together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or R¹¹ and R²¹, R¹² and R²², R²¹ and R³¹, and/or R²² and R³², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

More preferably, Y is O.

In another preferred embodiment, the compound of Formula III has the Formula IHb; wherein Y is O or S;

R¹¹, R²¹ and R³¹ are -H, and R¹², R²² and R³² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; wherein R¹, R², R³ and R⁴ are as defined for Formula I; or R and R and/or R" and R together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

More preferably, Y is O.

In another preferred embodiment, the compound of Formula III has the Formula IHb; wherein Y is O or S; R¹¹, R²¹ and R³¹ are -H, and R¹², R²² and R³² are each independently selected from the group consisting of -H, -N₃, -OR² and -NR³R⁴, wherein R², R³ and R⁴ at each occurrence are each independently selected from -H, -R⁸, -C(X)R⁸ and -C(X)XR⁸; X at each occurrence is independently selected from O, NH, NR⁹ and S; and R and R at each occurrence are independently selected from -H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxide, substituted alkoxide, sulfur, substituted sulfur, silicon, substituted silicon, boron, substituted boron, phosphorus, substituted phosphorus and metal.

More preferably, Y is O.

R¹¹, R²¹ and R³¹ are -H;

R¹² is -OH; and

R²² and R³² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; wherein R¹, R², R³ and R⁴ are as defined for

Formula I.

More preferably, Y is O.

In another preferred embodiment, the compound of Formula III has the Formula IHb; wherein Y is O or S; R¹¹, R²¹ and R³¹ are -H; R¹² and R²² are -OH; and

More preferably, Y is O.

In another preferred embodiment, the compound of Formula III has the Formula HIb; wherein Y is O or S;

R¹¹, R²¹ and R³¹ are -H; and R¹², R²² and R³² are -OH.

More preferably, Y is O. In another preferred embodiment, the compound of Formula III has the Formula IHb; wherein Y is O or S;

R¹¹, R²¹, R³¹ and R³² are -H; and

R¹² and R²² are -OH.

More preferably, Y is O.

In another preferred embodiment, the compound of Formula III has the Formula IHc:

wherein Y is O or S;

R¹¹, R¹², R²¹, R²², R³¹, R³², R⁴¹ and R⁴² are each independently selected from the group consisting of -H₅ -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; wherein R¹, R², R³ and R⁴ are as defined for Formula I; or R¹¹ and R¹², R²¹ and R²², R³¹ and R³², and/or R⁴¹ and R⁴², together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or R¹¹ and R²¹, R¹² and R²², R²¹ and R³¹, R²² and R³², R³¹ and R⁴¹, and/or R³² and R⁴², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

More preferably, Y is O.

In another preferred embodiment, the compound of Formula III has the Formula IIIc; wherein Y is O or S;

R¹¹, R²ⁱ, R³¹ and R⁴¹ are -H, and R¹², R²², R³² and R⁴² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; wherein R¹, R², R³ and R⁴ are as defined for Formula I; or R¹² and R²², R²² and R³², and/or R³² and R⁴², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, siibstituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

More preferably, Y is O.

In a further preferred embodiment, the compound of Formula III has the Formula IHc; wherein Y is O or S;

R¹¹, R²¹, R³¹ and R⁴¹ are -H, and R¹², R²², R³² and R⁴² are each independently selected from the group consisting of -H, -N₃, -OR² and -NR³R⁴, wherein R², R³ and R⁴ at each occurrence are each independently selected from -H, -R⁸, -C(X)R⁸ and -C(X)XR⁸; X at each occurrence is independently selected from O, NH, NR⁹ and S; and R⁸ and R⁹ at each occurrence are independently selected from -H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxide, substituted alkoxide, sulfur, substituted sulfur, silicon, substituted silicon, boron, substituted boron, phosphorus, substituted phosphorus and metal.

More preferably, Y is O.

In another preferred embodiment, the compound of Formula III has the Formula IHc; wherein Y is O or S;

R¹¹, R²¹, R³¹ and R⁴¹ are -H;

R¹² is -OH; and R ₅ R and R are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; wherein R¹, R², R³ and R⁴ are as defined for Formula I.

More preferably, Y is O.

R¹¹, R²¹, R³¹ and R⁴¹ are -H;

R¹² and R²² are -OH; and

R³² and R⁴² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; wherein R¹, R², R³ and R⁴ are as defined for Formula I. More preferably, Y is O.

R¹¹, R²¹, R³¹ and R⁴¹ are -H; and R¹², R²², R³² and R⁴² are -OH.

More preferably, Y is O.

In one embodiment, the compound of Formula I is obtained by reacting a compound of Formula II as in the first aspect.

In one embodiment, the halogen source is selected from the group consisting of NIS, NBS, NCS, I₂, Br₂, Cl₂, and mixtures of any two or more thereof. Preferably, the halogen source is I₂.

In one embodiment, the source of carbonate is selected from the group consisting OfLiHCO₃, Li₂CO₃, NaHCO₃, Na₂CO₃, KHCO₃, K₂CO₃, and mixtures of any two or more thereof. Preferably, the source of carbonate is NaHCO₃.

In one embodiment, the source of carbon dioxide is selected from the group consisting of carbon dioxide gas, liquid carbon dioxide, solid carbon dioxide, and mixtures of any two or more thereof.

In one embodiment, the source of carbon disulfide is CS₂.

The invention also provides a compound of Formula III, or a salt, solvate or hydrate thereof, when prepared by a method of the invention.

In a preferred embodiment, the compound of Formula I is enantiopure and the resulting compound of Formula III is chiral. If necessary, the compound of Formula I may be resolved into enantiomers using methods known to those persons skilled in the art.

In another preferred embodiment, the compound of Formula I is stereoisomerically pure and the resulting compound of Formula III is stereoisomerically pure.

In a preferred embodiment, the halogen-substituted cyclic acetal or derivative thereof is enantiopure and the reactions are stereo- and regioselective, such that the resulting cyclic carbamate or cyclic dithiocarbamate is chiral.

In a preferred embodiment, the halogen-substituted cyclic acetal or derivative thereof is stereoisomerically pure and the reactions are stereo- and regioselective, such that the resulting cyclic carbamate or cyclic dithiocarbamate is stereoisomerically pure.

A preferred embodiment of the third aspect provides a method for preparing a cyclic carbamate, or a salt, solvate or hydrate thereof, the method comprising: reacting a halogen-substituted cyclic acetal or a derivative thereof with a reaction metal, a source of ammonia and a hydride source to provide an alkenylamine; reacting the alkenylamine with a halogen source, a base and a source of carbonate or a source of carbon dioxide to provide the cyclic carbamate; optionally converting the cyclic carbamate into a salt, solvate or hydrate thereof; and optionally isolating the cyclic carbamate or salt, solvate or hydrate thereof.

In a fourth aspect, the present invention provides a method for preparing a 1,2-aminoalcohol or

1,2-aminothiol, or a salt, solvate or hydrate thereof, the method comprising: reacting an alkenylamine with a halogen source, a base and a source of carbonate or a source of carbon dioxide or a source of carbon disulfide to provide a cyclic carbamate or cyclic dithiocarbamate; deprotecting the cyclic carbamate or cyclic dithiocarbamate to provide the 1,2-aminoalcohol or

In a preferred embodiment, the alkenylamine is enantiopure and the reactions are stereo- and regioselective, such that the resulting 1,2-aminoalcohol or 1,2-aminothiol is chiral.

In another preferred embodiment, the alkenylamine is stereoisomerically pure and the reactions are stereo- and regioselective, such that the resulting 1,2-aminoalcohol or 1,2-aminothiol is stereoisomerically pure.

One embodiment of the fourth aspect of the invention is a method for preparing a compound of Formula IV:

or a salt, solvate or hydrate thereof; wherein Y is O or S;

L is selected from the group consisting of:

-C(Rⁿ)(R¹²)C(R²¹)(R²²)C(R³¹)(R³²)C(R⁴¹)(R⁴²)C(R⁵¹)(R⁵²)-; -C(R¹¹)(R¹²)C(R²¹)(R²²)C(R³¹)(R³²)C(R⁴¹)(R⁴²)-;

-C(R¹¹)(R¹²)C(R²¹)(R²²)C(R³¹)(R³²)-; and

-C(R¹¹XR¹^C(R²¹XR²²)-; wherein R¹¹, R¹², R²¹, R²², R³¹, R³², R⁴¹, R⁴², R⁵¹ and R⁵² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; or R¹¹ and R¹², R²¹ and R²², R³¹ and R³², R⁴¹ and R⁴², and/or R⁵¹ and R⁵², together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or R¹¹ and R²¹, R¹² and R²², R²¹ and R³¹, R²² and R³², R³¹ and R⁴¹, R³² and R⁴², R⁴¹ and R⁵¹, and/or R⁴² and R⁵², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl; or R¹ ' and R¹², R²¹ and R²², R³¹ and R³², R⁴¹ and R⁴², and/or R⁵¹ and R⁵² together form a

=C(R⁵)₂, =CR⁶(XR⁷), or =C(XR⁷)₂ group; wherein R¹, R², R³, R⁴, R⁵, R⁶ and R⁷ at each occurrence are independently selected from -H, -CN, -R⁸, -C(X)R⁸, -C(X)XR⁸, -C(R⁸)₃, -C(R⁸)₂XR⁸, -CR⁸(XR⁸)₂ and -C(XR⁸)₃; wherein X at each occurrence is independently selected from O, NH, NR⁹ and S; and R⁸ and R⁹ at each occurrence are independently selected from -H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, sulfur, substituted sulfur, silicon, substituted silicon, boron, substituted boron, phosphorus, substituted phosphorus and metal; or R³ and R⁴ together form a =C(R⁵)₂ , =CR⁶(XR⁷), or =C(XR⁷)₂ group; the method comprising: reacting a compound of Formula I, as defined above, with a halogen source, a base and a source of carbonate or a source of carbon dioxide or a source of carbon disulfide to provide a compound of Formula III, as defined above; deprotecting the compound of Formula III to provide the compound of Formula IV; optionally converting the compound of Formula IV into a salt, solvate or hydrate thereof; and optionally isolating the compound of Formula IV or salt, solvate or hydrate thereof.

Preferably, Y is O.

In a preferred embodiment, the compound of Formula IV is selected from the group consisting of the compounds of Formula IVa, IVb and IVc:

In a further preferred embodiment, the compound of Formula IV is selected from the group consisting of the compounds of Formula IVa and IVb.

In another preferred embodiment, the compound of Formula IV is selected from the group consisting of the compounds of Formula IVa', IVb' and IVc':

In another preferred embodiment, the compound of Formula IV is selected from the group consisting of the compounds of Formula IVa' and IVb'. In another preferred embodiment, the compound of Formula IV has the Formula IVa:

wherein Y is O or S;

1 1 10 OI OO

R , R , R and R are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; wherein R¹, R², R³ and R⁴ are as defined for Formula I;

1 1 10 OI OO or R and R and/or R and R , together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or R¹¹ and R²¹ and/or R¹² and R²², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

In a further preferred embodiment, the compound of Formula IV has the Formula IVa; wherein

1 1 01 I O OO

R and R are -H, and R and R are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; wherein R¹, R², R³ and R⁴ are as defined for Formula I; or R¹² and R²², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

More preferably, Y is O.

In another preferred embodiment, the compound of Formula IV has the Formula IVa; wherein Y is O or S;

1 1 O l 10 OO

X at each occurrence is independently selected from O, NH, NR⁹ and S; and R⁸ and R⁹ at each occurrence are independently selected from -H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxide, substituted alkoxide, sulfur, substituted sulfur, silicon, substituted silicon, boron, substituted boron, phosphorus, substituted phosphorus and metal.

More preferably, Y is O.

R¹¹ and R²¹ are -H;

R¹² is -OH; and

R¹, R², R³ and R⁴ are as defined for Formula I.

More preferably, Y is O.

R¹¹ and R²¹ are -H; and

R¹² and R²² are -OH.

More preferably, Y is O.

R¹¹, R²¹ and R²² are -H; and

R¹² is -OH.

More preferably, Y is O.

In another preferred embodiment, the compound of Formula IV has the Formula IVb:

wherein Y is O or S;

R , R , R , R , R and R are each independently selected from the group consisting of -H, -R¹ , -OR², -SR², -NR³R⁴, -NO₂ and -N₃ ; wherein R¹ , R², R³ and R⁴ are as defined for Formula I; or R¹¹ and R¹², R²¹ and R²², and/or R³¹ and R³², together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or alternatively R¹¹ and R²¹, R¹² and R²², R²¹ and R³¹, and/or R²² and R³², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

More preferably, Y is O.

In another preferred embodiment, the compound of Formula IV has the Formula IVb; wherein Y is O or S;

R¹¹, R²¹ and R³¹ are -H, and R¹², R²² and R³² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; wherein R¹, R², R³ and R⁴ are as defined for Formula I; or R and R and/or R and R together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

More preferably, Y is O.

In another preferred embodiment, the compound of Formula IV has the Formula IVb; wherein Y is O or S; R¹¹, R²¹ and R³¹ are -H, and R¹², R²² and R³² are each independently selected from the group consisting of -H, -N₃, -OR² and -NR³R⁴, wherein R², R³ and R⁴ at each occurrence are each independently selected from -H, -R⁸, -C(X)R⁸ and -C(X)XR⁸;

X at each occurrence is independently selected from O, NH, NR⁹ and S; and

R⁸ and R⁹ at each occurrence are independently selected from -H, alkyl, substituted alkyl, ^■ alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxide, substituted alkoxide, sulfur, substituted sulfur, silicon, substituted silicon, boron, substituted boron, phosphorus, substituted phosphorus and metal.

More preferably, Y is O. In another preferred embodiment, the compound of Formula IV has the Formula IVb; wherein Y is O or S;

R¹¹, R²¹ and R³¹ are -H; R¹² is -OH; and R²² and R³² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; wherein R¹, R², R³ and R⁴ are as defined for Formula I.

More preferably, Y is O.

R¹¹, R²¹ and R³¹ are -H;

R¹² and R²² are -OH; and

R³² is selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; wherein

R¹, R², R³ and R⁴ are as defined for Formula I.

More preferably, Y is O.

R¹¹, R²¹ and R³¹ are -H; and

R¹², R²² and R³² are -OH.

More preferably, Y is O.

R¹¹, R²¹, R³¹ and R³² are -H; and

R¹² and R²² are -OH.

More preferably, Y is O. In another preferred embodiment, the compound of Formula IV has the Formula IVc:

wherein Y is O or S;

R¹¹, R¹², R²¹, R²², R³¹, R³², R⁴¹and R⁴² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; wherein R¹, R², R³ and R⁴ are as defined for Formula I; or R¹¹ and R¹², R²¹ and R²², R³¹ and R³², and/or R⁴¹ and R⁴², together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or R¹¹ and R²¹, R¹² and R²², R²¹ and R³¹, R²² and R³², R³¹ and R⁴¹, and/or R³² and R⁴², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

More preferably, Y is O.

In another preferred embodiment, the compound of Formula IV has the Formula IVc; wherein Y is O or S;

R¹¹, R²¹, R³¹ and R⁴¹ are -H, and R¹², R²², R³² and R⁴² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; wherein R¹, R², R³ and R⁴ are as defined for Formula I; or R¹² and R²², R²² and R³², and/or R³² and R⁴², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

More preferably, Y is O.

In another preferred embodiment, the compound of Formula IV has the Formula IVc; wherein Y is O or S; R¹¹, R²¹, R³¹ and R⁴¹ are -H, and R¹², R²², R³² and R⁴² are each independently selected from the group consisting of -H, -N₃, -OR² and -NR³R⁴, wherein R², R³ and R⁴ at each occurrence are each independently selected from -H, -R⁸, -C(X)R⁸ and -C(X)XR⁸; X at each occurrence is independently selected from O, NH, NR⁹ and S; and R⁸ and R⁹ at each occurrence are independently selected from -H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxide, substituted alkoxide, sulfur, substituted sulfur, silicon, substituted silicon, boron, substituted boron, phosphorus, substituted phosphorus and metal.

More preferably, Y is O.

R^u, R²¹, R³¹ and R⁴¹ are -H;

R¹² is -OH; and

Formula I.

More preferably, Y is O.

In another preferred embodiment, the compound of Formula IV has the Formula IVc; wherein Y is O or S; R¹¹, R²¹, R³¹ and R⁴¹ are -H; R¹² and R²² are -OH; and

More preferably, Y is O.

R¹¹, R²¹, R³¹ and R⁴¹ are -H; and

R¹², R²², R³² and R⁴² are -OH.

More preferably, Y is O. It will be appreciated that the compounds of Formula I, II, III and IV are contemplated as chemically feasible compounds.

In one embodiment of the invention, the group L includes five or fewer spiro rings and/or fused rings. In another embodiment of the invention, the group L includes four or fewer spiro rings and/or fused rings. In another embodiment of the invention, the group L includes three or fewer spiro rings and/or fused rings. In another embodiment of the invention, the group L includes two or fewer spiro rings and/or fused rings. In another embodiment of the invention, the group L includes one or no spiro rings and/or fused rings. In another embodiment of the invention, the group L includes no spiro rings and/or fused rings.

The compound of Formula III may be deprotected to provide the compound of Formula IV using known methods. Such methods include, but are not limited to: reactions under alkaline conditions, for example with sodium hydroxide in ethanol at reflux temperature; reactions under acidic conditions, for example with 6N aqueous HCl at reflux temperature; and reaction with peroxides, for example LiOOH or H₂O₂ZLiOH.

In one embodiment, the method further comprises reacting a compound of Formula II, as defined above, with a reaction metal, a source of ammonia and a hydride source to provide the compound of Formula I.

The invention also provides a compound of Formula IV, or a salt, solvate or hydrate thereof, when prepared by a method of the invention.

In a preferred embodiment, the compound of Formula I is enantiopure and the resulting compound of Formula IV is chiral. If necessary, the compound of Formula I may be resolved into enantiomers using methods known to those persons skilled in the art.

In another preferred embodiment, the compound of Formula I is stereoisomerically pure and the resulting compound of Formula IV is stereoisomerically pure.

In a fifth aspect, the present invention provides a method for preparing a 1,2-aminoalcohol or 1 ,2-aminothiol, or a salt, solvate or hydrate thereof, the method comprising: reacting a halogen-substituted cyclic acetal or a derivative thereof with a reaction metal, a source of ammonia and a hydride source to provide an alkenylamine; reacting the alkenylamine with a halogen source, a base and a source of carbonate or a source of carbon dioxide or a source of carbon disulfide to provide a cyclic carbamate or cyclic dithiocarbamate; deprotecting the cyclic carbamate or cyclic dithiocarbamate to provide the 1,2-aminoalcohol or 1,2-aminothiol; optionally converting the 1,2-aminoalcohol or 1,2-aminothiol into a salt, solvate or hydrate thereof; and optionally isolating the 1,2-aminoalcohol or 1,2-aminothiol or salt, solvate or hydrate thereof.

In a preferred embodiment, the halogen-substituted cyclic acetal or derivative thereof is enantiopure and the reactions are stereo- and regioselective, such that the resulting 1,2-aminoalcohol or 1,2-aminothiol is chiral.

In another preferred embodiment, the halogen-substituted cyclic acetal or derivative thereof is stereoisomerically pure and the reactions are stereo- and regioselective, such that the resulting 1,2-aminoalcohol or 1,2-aminothiol is stereoisomerically pure.

In one embodiment of the second, third, fourth and/or fifth aspects, the alkenylamine is reacted with a halogen source, a base and a source of carbonate or a source of carbon disulfide to provide a cyclic carbamate or cyclic dithiocarbamate.

In one embodiment of the second, third, fourth and/or fifth aspects, a compound of Formula I is reacted with a source of carbonate or a source of carbon disulfide to provide a compound of Formula III.

In another embodiment of the second, third, fourth and/or fifth aspects, the alkenylamine is reacted with a halogen source, a base and a source of carbonate to provide a cyclic carbamate.

In another embodiment of the second, third, fourth and/or fifth aspects, the alkenylamine is reacted with a halogen source, a base and a source of carbon dioxide to provide a cyclic carbamate.

In another embodiment of the second, third, fourth and/or fifth aspects, the alkenylamine is reacted with a halogen source, a base and a source of carbon disulfide to provide a cyclic dithiocarbamate.

A preferred embodiment of the fifth aspect provides a method for preparing a 1,2-aminoalcohol, or a salt, solvate or hydrate thereof, the method comprising: reacting a halogen-substituted cyclic acetal or a derivative thereof with a reaction metal, a source of ammonia and a hydride source to provide an alkenylamine; reacting the alkenylamine with a halogen source, a base and a source of carbonate or a source of carbon dioxide to provide a cyclic carbamate; deprotecting the cyclic carbamate to provide the 1 ,2-aminoalcohol; optionally converting the 1,2-aminoalcohol into a salt, solvate or hydrate thereof; and optionally isolating the 1,2-aminoalcohol or salt, solvate or hydrate thereof.

In another aspect, the present invention provides the halogen-substituted cyclic acetal:

In a preferred embodiment, the halogen-substituted cyclic acetal has the following stereochemistry :

In another aspect, the present invention provides an alkenylamine selected from the group consisting of:

In a preferred embodiment, the alkenylamine is selected from the group consisting of:

In another aspect, the present invention provides a cyclic carbamate selected from the group consisting of:

In a preferred embodiment, the cyclic carbamate is selected from the group consisting of:

In another preferred embodiment, the cyclic carbamate is selected from the group consisting of:

Those persons skilled in the art will appreciate that, in the course of preparing the compounds useful in the invention, the functional groups of intermediate compounds may need to be protected by protecting groups. Functional groups which it may be desirable to protect include, but are not limited to: hydroxyl; amino; and carboxylic acid groups. Protecting groups may be added and removed in accordance with techniques that are well known to those persons skilled in the art. The use of protecting groups is described in, for example, J. W. F. McOmie (ed.),

Protective Groups in Organic Chemistry, Plenum Press, London, 1973 and T. W. Greene and P. G. M. Wutz, Protective Groups in Organic Synthesis, 3^rd edition, Wiley, New York, 1999. Those persons skilled in the art will be able to select suitable solvents and conditions for the reactions within the scope of the invention without undue experimentation. The selection of solvents will be influenced by, for example, reagent and product solubility considerations. In some embodiments, the use of solvent mixtures will be advantageous.

In one embodiment, the solvent is an aqueous solvent system, which typically comprises either water or a mixture of water and one or more suitable organic solvent. The organic solvent may be miscible or immiscible with water. In some embodiments, the aqueous solvent system comprises a two phase solvent mixture and includes a phase transfer catalyst. Suitable organic solvents include, but are not limited to: alcohols, for example methanol and ethanol; acetonitrile; dioxane; tetrahydrofuran; dimethyl formamide; and dimethyl sulfoxide.

The reaction may be carried out at ambient temperature. In alternatives embodiments, the reaction mixture may be heated or cooled, using standard techniques.

The product compound may be isolated from the reaction mixture using standard techniques known in the art. Such techniques include, but are not limited to: filtration; solvent extraction; and evaporation.

The product compound may optionally be purified, using standard techniques known in the art, either as part of, or following isolation from the reaction mixture.

The following non-limiting examples are provided to illustrate the present invention and in no way limit the scope thereof.

EXAMPLES

The precursor cyclic acetal compounds 1, 5, 9, 13, 17, and 21 were prepared using a literature procedure (Skaanderup, P. R.; Poulsen, C. S.; Hyldtoft, L.; Jørgensen, M. R.; Madsen, R. Synthesis 2002, 12, 1721-1727). Cyclic acetal 25 was prepared by an analogous procedure.

Example 1

(2S,3S)-l-Amino-pent-4-ene-2,3-diol (2). To a solution of halogenated cyclic acetal 1 (60 mg, 0.22 mmol) in a saturated solution OfNH₄OAc in EtOH (4 mL) was added Zn (72 mg, 1.1 nimol), NaCNBH₃ (47 mg, 0.4 mmol) and 30% aqueous NH₃ (1.6 mL). The mixture was stirred at reflux for 18 h, cooled to room temperature and concentrated under reduced pressure. The residue was redissolved in /PrOH and a solution of 20% HCl in /PrOH was added (4.6 g, 28 mmol). The solution was filtered through celite and concentrated under reduced pressure. The filtrate was dissolved in /PrOH (4 mL) and filtered through cotton wool. The solution was dry loaded on to silica gel and purified by gradient flash chromatography (DCM/EtOH/MeOH/30% aqueous NH₃, from 25/2/2/1 to 5/2/2/1, v/v/v/v) to give the alkenylaniine 2 as the HCl salt (32 mg, 0.21 mmol, 95%). R/= 0.37 (DCM/EtOH/MeOH/30% aqueous NH₃, 5/2/2/1, v/v/v/v); [α]_D ²⁰ - -40.0 (c = 0.07, EtOH); ¹H NMR (300 MHz, D₂O) δ 5.71 (ddd, J_3,4 = 6.4 Hz, J₄,_5-c* = 10.5 Hz, = 17.1 Hz, IH, H-4), 5.34 (d, J₄, ₅._trans - 17.1 Hz, IH, E-5-trans), 5.28 (d, J₄,₅-cis = 10.5 Hz, IH, H-5-cis), 4.10 (dd, J_2,3 = 5.0 Hz, J_3^4 = 6.4 Hz, IH, H-3), 4.05 (s, IH, NH), 3.81 (ddd, J_la,2 = 3.3 Hz, J_2;3 = 5.0 Hz, J_lb;2 = 9.7 Hz, IH, H-2), 3.15 (dd, J_la>2 = 3.3 Hz, J_1Mb = 13.2 Hz₅ IH₅ H-Ia), 2.98 (dd₅ J_lb,₂ = 9.7 Hz₅ J_la,_lb = 13.2 Hz, IH, H-Ib); ¹³C NMR (75 MHz, D₂O) δ 135.8 (C4), 117.9 (C5), 73.9 (C3), 72.0 (CZ), 42.0 (Cl); IR (film) 3405, 3212, 2888, 1555, 1434, 1183, 1127, 1016, 838 cm^"1. HRMS(ESI) m/z calcd. for [C₅H₁₂O₂N]⁺: 118.0863, obsd.: 118.0871.

(2S,3S)-l-Amino-pent-4-ene-2,3-diol (2) was also prepared using the following procedure. To a solution of halogenated cyclic acetal 1 (60.1 mg, 0.22 mmol) in a saturated solution OfNH₄OAc in EtOH (5 mL) was added activated Zn (72.0 mg, 1.1 mmol), NaCNBH₃ (42 mg, 0.66 mmol) and 30% aqueous NH₃ (2 mL). The mixture was stirred at reflux for 18 h, cooled to room temperature and concentrated under reduced pressure. The residue was redissolved in water and purified directly by ion-exchange chromatography (Dowex H⁺). The product was eluted using 5- 15% aqueous NH₃. Alkenylamine 2 was obtained as the HCl salt (32 mg, 0.21 mmol, 95%).

(6S,7S,7aR)₇6,7-Dihydroxy-tetrahydro-pyrroIo[l,2-c]oxazol-3-one (3). To a solution of alkenylamine 2 hydrochloride (8 mg, 0.05 mmol) in water (0.25 mL) was added NaHCO₃ (6.4 mg, 0.075 mmol) and I₂ (14 mg, 0.055 mmol). The solution was stirred 18 h at room temperature then filtered and concentrated under reduced pressure. Purification of the residue by silica gel chromatography (hexanes/EtOAc, 1/3, v/v) gave carbamate 3 as a white powder (8 mg, 0.05 mmol, 99%). [α]_D ¹⁹ = -26.1 (c = 0.4, EtOH); ¹H NMR (500 MHz, D₂O) δ 4.61 (t, J₄,_5a = J_5aj5b = 9.1 Hz, IH, H-5a), 4.49 (dd, J₄,_5b = 3.3 Hz, J_5a,₅b = 9.1 Hz, IH, H-5b), 4.36 (d, J_la>2 = 5.2 Hz, IH, H-2), 4.27 (dt, J₄,_5a = 8.5 Hz, J_4;5b = J3,4 = 3.3 Hz, IH, H-4), 4.01 (d, J₃,₄ = 3.3 Hz, IH, H-3), 3.77 (dd, J_la,₂ = 5.2 Hz₅ J_la,_lb = 12.7 Hz, IH, H-Ia), 3.10 (d, J_la,_lb = 12.7 Hz, IH₃ H-Ib); ¹³C NMR (75 MHz, D₂O) δ 164.4 (C6), 76.4 (C2), 74.2 (C3), 63.9 (C5), 62.0 (C4), 52.2 (Cl); IR (film) 3363, 2947, 2835, 1652, 1449, 1412, 1205, 1113, 1018 cm^"1. HRMS(ESI) m/z calcd. for [C₆H₁₀O₄N]⁺: 160.0604, obsd.: 160.0605.

The procedure above was repeated using alkenylamine 2 hydrochloride (7.5 mg, 0.050 mmol) in water (1 mL), NaHCO₃ (6.3 mg, 0.075 mmol), and I₂ (14 mg, 0.055 mmol) to give carbamate 3 as an amorphous white powder (8 mg, 0.050 mmol, 99%).

(2R,3S,4S)-2-Hydroxymethyl-pyrrolidine-3,4-diol (4). To a solution of carbamate 3 (6.6 mg, 0.042 mmol) in EtOH (0.21 mL) was added NaOH (17 mg, 0.42 mmol). The solution was stirred at reflux for 2 h, cooled and purified by ion-exchange chromatography (Dowex H⁺) eluting with 5-15% aqueous NH₃. HCl in isopropanol was added and concentration in vacuo gave 4 as the HCl salt (7 mg, 0.04 mmol, 99%). R₇= 0.90 (DCM/EtOH/MeOH/30% aqueous NH₃, 5/2/2/1, v/v/v/v); [α]_D ²⁰ = -6.4 (c = 0.5, H₂O); ¹H NMR (300 MHz, D₂O) δ 4.37 (d, J_la>2 = 4.4 Hz, IH, H-2), 4.30 (s, IH, H-3), 4.01 (m, IH, H-5a), 3.88 (m, 2H, H-4 and H-5b), 3.64 (dd, J_la>2 = 4.4 Hz, J_1Mb = 13.0 Hz, IH, H-Ia), 3.28 (d, J_la,_lb = 13.0 Hz, IH, H-Ib); ¹³C NMR (75 MHz, D₂O) δ 74.3 (C2 or 3), 74.2 (C3 or 2), 62.9 (C4), 57.2 (C5), 50.4 (Cl). IR (film) 3334, 3172, 2974, 2886, 1380, 1328, 1088, 1045 cm^"1. HRMS(ESI) m/z calcd. for [C₅H₁₂O₃N]⁺: 134.0812, obsd.: 134.0818.

The procedure above was repeated using carbamate 3 (6.5 mg, 0.041 mmol) in EtOH (1 mL) and NaOH (16 mg, 0.4 mmol) to give 4 as the HCl salt (7.0 mg, 41 μmol, 99%).

Example 2

5 6 7 8

(2S,3R)-l-Amino-pent-4-ene-2,3-diol (g^ -p_{0 a} solution of halogenated cyclic acetal 5 (51 mg, 0.19 mmol) in a saturated solution OfNH₄OAc inEtOH (4 mL) was added Zn (61 mg, 0.95 mmol), NaCNBH₃ (40 mg, 0.4 mmol) and 30% aqueous NH₃ (1.6 mL). The mixture was stirred at reflux for 18 h, cooled to room temperature and concentrated under reduced pressure. The residue was redissolved in /PrOH and a solution of 20% HCl in /PrOH was added (3.9 g, 23 mmol). The solution was filtered through celite and concentrated under reduced pressure. The filtrate was dissolved in /PrOH (4 niL) and filtered through cotton wool. The solution was dry loaded on to silica gel and purified by gradient flash chromatography (DCM/EtOH/MeOH/30% aqueous NH₃, from 25/2/2/1 to 5/2/2/1, v/v/v/v) to give the alkenylamine 6 as the HCl salt (26 mg, 0.17 mmol, 91%). R/= 0.41 (DCM/EtOH/MeOH/30% aqueous NH₃, 5/2/2/1, v/v/v/v); [α]_D ¹⁸ = +8.2 (c = 0.28, EtOH); ¹H NMR (300 MHz, D₂O) δ 5.88 (ddd, J₃,₄ = 6.6 Hz, J_4;5-c/, = 10.5 Hz, = 17.1 Hz, IH, H-4), 5.35 (d, J_A>tram = 17.1 Hz, IH, U-5-tmns), 5.31 (d, J₄,_5-c/, = 10.5 Hz, IH, n-5-cis), 4.12 (dd, J₂,₃ = 5.6 Hz, J_3,4 - 6.6 Hz, IH, H-3), 3.81 (ddd, J_la>2 = 3.0 Hz, J_2,3 - 5.6 Hz, J_lb;2 = 9.7 Hz, IH, H-2), 3.23 (dd, Ji_a,2 = 3.0 Hz, Ji_Mb = 13.2 Hz, IH, H-Ia), 2.95 (dd, Ji_b,2 = 9.7 Hz, Ji_aj_b = 13.2 Hz, IH, H-Ib); ¹³C NMR (75 MHz, D₂O) δ 135.4 (C4), 118.3 (C5), 74.0 (C3), 69.8 (C2), 41.1 (Cl); IR (film) 3345, 2946, 2835, 1651, 1450, 1018 cm-¹. HRMS(ESI) m/z calcd. for [C₅H₁₂O₂N]⁺: 118.0863, obsd.: 118.0873.

(2S,3R)-l-Amino-pent-4-ene-2,3-diol (6) was also prepared using the following procedure. To a solution of halogenated cyclic acetal 5 (51.2 mg, 0.19 mmol) in a saturated solution OfNH₄OAc inEtOH (4 mL) was added activated Zn (62 mg, 0.95 mmol), NaCNBH₃ (36.4 mg, 0.57 mmol) and 30% aqueous NH₃ (1.5 mL). The mixture was stirred at reflux for 18 h, cooled to room temperature and concentrated under reduced pressure. The residue was redissolved in H₂O and purified directly by ion-exchange chromatography (Dowex H⁺). The product was eluted using 5- 15% aqueous NH₃. Alkenylamine 6 was obtained as the HCl salt (26 mg, 0.17 mmol, 91%).

(6S,7R,7aS)-6,7-Dihydroxy-tetrahydro-pyrrolo[l,2-c]oxazol-3-one (7). To a solution of alkenylamine 6 hydrochloride (30 mg, 0.20 mmol) in water (1 mL) was added NaHCO₃ (25 mg, 0.30 mmol) and I₂ (55 mg, 0.22 mmol). The solution was stirred 18 h at room temperature then filtered and concentrated under reduced pressure. Purification of the residue by silica gel chromatography (hexanes/EtOAc, 1/3, v/v) gave carbamate 7 as a white powder (29 mg, 0.19 mmol, 93%). [α]_D ¹⁹ = +32.2 (c = 0.3, EtOH); ¹H NMR (500 MHz, D₂O) δ 4.52 (m, 3H, H-2, H- 5a and H-5b), 4.14 (ddd, J₃,₄ = 3.1 Hz, J_4> = 5.0 Hz, J_4;5b = 7.9 Hz, IH, H-4), 4.01 (dd, J_3j4 = 3.1 Hz, J_2,3 = 3.3 Hz, IH, H-3), 3.51 (dd, J_la,2 = 8.1 Hz, J_Ia,_lb = 10.8 Hz, IH, H-Ia), 3.15 (dd, J_lb,₂ = 7.9 Hz, Ji_a,i_b = 10.8 Hz, IH, H-Ib); ¹³C NMR (75 MHz₅ D₂O) δ 164.1 (C6), 73.2 (C2), 70.6 (C3), 64.3 (C5), 61.5 (C4), 48.6 (Cl); IR (film) 3332, 2977, 1717, 1474, 1411, 1250, 1130, 1068 cm-¹. HRMS(ESI) m/z calcd. for [C₆H₉O₄NNa]⁺: 182.0424, obsd.: 182.0429. The procedure above was repeated using alkenylamine 6 hydrochloride (30 mg, 0.20 mmol) in water (1 niL), NaHCO₃ (25 mg, 0.3 mmol), and I₂ (55.8 mg, 0.22 mmol) to give carbamate 7 as an amorphous white powder (29 mg, 0.18 mmol, 93%).

(2S,3Rj4S)-2-Hydroxymethyl-pyrrolidine-3,4-diol (8). To a solution of carbamate 7 (6.4 mg, 0.040 mmol) in EtOH (0.20 mL) was added NaOH (16 mg, 0.40 mmol). The solution was stirred at reflux for 2 h, cooled and purified by ion-exchange chromatography (Dowex H⁺) eluting with 5-15% aqueous NH₃. HCl in isopropanol was added and concentration in vacuo gave 8 as the HCl salt (6.6 mg, 97%). R/= 0.11 (DCM/EtOH/MeOH/30% aqueous NH₃, 5/2/2/1, v/v/v/v); [α]_D ¹⁹ = -22.4 (c = 0.3, H₂O); ¹H NMR (500 MHz, D₂O) δ 4.47 (dt, J_2>3 = 4.1 Hz, J_la,₂ = J_lb,₂ = 7.4 Hz, IH, H-2), 4.32 (t, J_2;3 = J_3;4 = 4.2 Hz, IH, H-3), 3.96 (dd, J₄,_5a = 5.0 Hz, J_5a,_5b = 12.1 Hz, IH, H-5a), 3.86 (dd, J_4j5b = 8.4 Hz, J_5aJSb = 12.1 Hz, IH, H-5b), 3.71 (ddd, J_3j4 = 4.2 Hz, J₄,5_a = 5.0 Hz, J₄,5b = 8.4 Hz, IH, H-4), 3.50 (dd, J_la,₂ = 7.4 Hz, J_la,_lb = 12.2 Hz, IH₅ H-Ia), 3.18 (dd, J_lb,₂ = 7.4 Hz, J_laαb = 12.2 Hz, IH, H-Ib); ¹³C NMR (75 MHz, D₂O) δ 69.9 (CZ), 69.7 (C3), 62.4 (C4), 57.6 (C5), 46.9 (Cl); IR (film) 3369, 3198, 2956, 2857, 1456, 1266, 1127, 1056 cm^"1. HRMS(ESI) m/z calcd. for [C₅Hi₂O₃N]⁺: 134.0812, obsd.: 134.0813.

The procedure above was repeated using carbamate 7 (6.4 mg, 40 μmol) in EtOH (1 mL) and NaOH (16 mg, 0.4 mmol) to give 8 as the HCl salt (6.6 mg, 39 μmol, 97%).

Example 3

9 10 11 12

(2R,3R)-l-Amino-pent-4-ene-2,3-diol (10). To a solution of halogenated cyclic acetal 9 (274 mg, 1 mmol) in a saturated solution OfNH₄OAc in EtOH (20 mL) was added activated Zn (327 mg, 5 mmol), NaCNBH₃ (188 mg, 3 mmol) and 30% aqueous NH₃ (8 mL). The mixture was stirred at reflux for 18 h, cooled to room temperature and concentrated under reduced pressure. The residue was redissolved in water and purified directly by ion-exchange chromatography (DoWeX H⁺). The product was eluted using 5-15% aqueous NH₃. Alkenylamine 10 was obtained as the HCl salt (143 mg, 93 mmol, 93%). R/= 0.61 (DCM/EtOH/MeOH/30% aqueous NH₃, 5/2/2/1, v/v/v/v); [α]_D ²⁰ = +50.6 (c = 1.0, EtOH); ¹H NMR (500 MHz, D₂O) δ 5.74 (ddd, J_3;4 = 5.3 Hz, J_4,5-c/, = 10.5 Hz, As-t_rans = 17.3 Hz, IH, H-4), 5.23 (d, J₄,_5-,_rarø = 17.3 Hz, IH, H-5- trans\ 5.17 (d, J₄,₅._c,-, - 10.5 Hz, IH, U-5-cis), 3.99 (t, J_3j4 = J₂,₃ = 5.3 Hz, IH, H-3), 3.70 (ddd, J_la,2 = 2.8 Hz, J₂,₃ = 5.3 Hz, J_lb,₂ = 9.9 Hz, IH, H-2), 3.03 (dd, J_la,₂ = 9.9 Hz, J_la,_lb = 13.1 Hz₅ IH, H-Ia), 2.87 (dd, J_la,₂ = 2.8 Hz, J_la>lb = 13.1 Hz, IH, H-Ib); ¹³C NMR (125 MHz, D₂O) δ 135.4 (CA), 118.2 (C5), 73.7 (C3), 69.7 (C2), 41.5 (Cl); IR (film) 3412, 3252, 3045, 1632, 1432, 1013 cm^"1. HRMS(ESI) m/z calcd. for [C₅H₁₂O₂N]⁺: 118.0868, obsd: 118.0869.

(6R,7R,7aR)-6,7-Dihydroxy-tetrahydro-pyrroIo[l,2-c]oxazoI-3-one (11). To a solution of the alkenylamine 10 hydrochloride (40 mg, 0.26 mmol) in water (1 mL) was added NaHCO₃ (25 mg, 0.39 mmol) and I₂ (73 mg, 0.29 mmol). The solution was stirred 18 h at room temperature then filtered and concentrated under reduced pressure. The product was purified by silica gel chromatography (hexanes/EtOAc, 1/3, v/v). Carbamate 11 was isolated as an amorphous white powder (30 mg, 0.19 mmol, 73%). [α]_D ¹⁸ = +20.1 (c - 0.6, EtOH); ¹H NMR (500MHz, D₂O) δ 4.51 (t, J4,_5a = J5a,_5b = 9.2 Hz, IH, H-5a) 4.38 (dd, J_5a,_5b = 9.2 Hz, J_4;5b ="2.9 Hz, IH, H-5b), 4.27 (d, J_la,2 = 5.1 Hz, IH, H-2), 4.17 (dt, J_4,5a = 9.2 Hz, J₄,_5b = J₃,₄ = 2.9 Hz, IH, H4), 3.90 (d, J₃,₄ - 2.9 Hz, IH, H-3), 3.67 (dd, J_la,2 = 5.1 Hz, Ji_Mb = 12.5 Hz, IH, H-Ia), 3.01 (d, Ji_Mb = 12.5 Hz, IH, H-Ib); ¹³C NMR (125 MHz, D₂O) δ 164.4 (C6), 76.5 (C2), 74.3 (C3), 64.0 (C5), 62.0 (C4), 52.2 (Cl); IR (film) 3372, 2954, 2845, 1715, 1635, 1416, 1253, 1079, 955 cm^"1. HRMS(ESI) m/z calcd. for [C₆H₉O₄NNa]⁺: 182.0424, obsd.: 182.0429.

(2S,3R,4R)-2-HydroxymethyI-pyrrolidine-3,4-dioI (12). To a solution of carbamate 11 (13 mg, 0.08 mmol) in EtOH (1 mL) was added NaOH (19 mg, 0.8 mmol). The solution was stirred at reflux for 2 h then cooled and purified directly by ion-exchange chromatography (Dowex H⁺). The product was eluted using 5-15% aqueous NH₃. 12 was isolated as the HCl salt (9.9 mg, 0.07 mmol, 90%). R₇= 0.21 (DCM/EtOH/MeOH/30% aqueous NH₃, 5/2/2/1, v/v/v/v); [α]_D ²⁰ = +8.2 (c=0.5, H₂O); ¹H NMR (500MHz, D₂O) δ 4.26 (d, J_la>2 = 4.5 Hz, IH, H-2), 4.19 (d, J_3j4 = 3.8 Hz, IH, H-3), 3.89 (dd, J₄,_5a = 5.5 Hz, J_5a>5b = 11.5 Hz, IH, H-5a), 3.77 (dd, J_4,5b = 7.7 Hz, J_5a,_5b = 11.5 Hz, IH, H-5b), 3.62 (ddd, J_3>4 = 3.8 Hz, J_4,5a = 5.5 Hz, J_4>5b = 7.7 Hz, IH, H-4), 3.46 (dd, J_la,₂ = 4.5 Hz, Ji_Mb = 12.8 Hz, IH, H-Ia), 3.04 (d, J_la,_lb = 12.8 Hz, IH, H-Ib); ¹³C NMR (125 MHz, D₂O) δ 74.6 (C2), 74.5 (C3), 62.5 (C4), 57.6 (C5), 50.4 (Cl); IR(film) 3317, 2944, 2832, 1654, 1449, 1415, 1113, 1021 cm^"1. HRMS(ESI) m/z calcd. for [C₅H₁₂O₃N]⁺: 134.0817, obsd.: 134.0817. Example 4

13 14 15 16

(R)-5-Amino-pent-l-en-3-ol (14). To a solution of halogenated cyclic acetal 13 (100 mg, 0.38 mmol) in a saturated solution OfNH₄OAc in EtOH (7.5 niL) was added activated Zn (124 mg, 1.9 mmol), NaCNBH₃ (73 mg, 1.14 mmol) and 30% aqueous NH₃ (3 mL). The mixture was stirred at reflux for 18 h, cooled to room temperature and concentrated under reduced pressure. The residue was redissolved in water and purified directly by ion-exchange chromatography (Dowex H⁺). The product was eluted using 5-15% aqueous NH₃. Alkenylamine 14 was obtained as the HCl salt (42 mg, 0.31 mmol, 81%). R/= 0.4 (DCM/EtOH/MeOH/30% aqueous NH₃, 5/2/2/1, v/v/v/v); [αJ_D ¹⁷ = -3.2 (c=0.1, EtOH); ¹H NMR (300MHz, D₂O) δ 5.35 (ddd, J_2a,3 = 6.06 Hz, J4,_5b =10.5 Hz, J₄,_5a = 17.3 Hz, IH, H4), 5.06 (dd, J_5a,_5b = 1.3 Hz, J₄,_5a = 17.3 Hz, IH, H-5a), 5.04 (dd, J_5a,_5b = 1.3 Hz, J₄,_5b = 10.5 Hz, IH, H-5b), 4.04 (dd, J_3;4= 6.06 Hz_., J_2,3 = 12.5 Hz, IH₅ H-3), 2.96 (m, 2H, H-I), 1.38 (m, 2H, H-2); ¹³C NMR (125 MHz, D₂O) δ 138.8 (C4), 115.8 (C5), 70.1 (C3), 36.3 (Cl), 32.9 (C2); IR (film), 3359, 3047, 2955, 2927, 2854, 1635, 1428, 1134, 1056 cm^"1. HRMS(ESI) m/z calcd. for [C₅H₁₂NO]⁺: 102.0919, obsd.: 102.0921.

(7S,7aS)-7-Hydroxy-tetrahydro-pyrrolo[l,2-c]oxazol-3-one (15). To a solution of the alkenylamine 14 hydrochloride (30 mg, 0.21 mmol) in water (1 mL) was added NaHCO₃ (20 mg, 0.32 mmol) and I₂ (59 mg, 0.23 mmol). The solution was stirred 18 h at room temperature then filtered and concentrated under reduced pressure. The product was purified by silica gel chromatography (hexanes/EtOAc, 1/3, v/v). Carbamate 15 was isolated as an amorphous white powder (33 mg, 0.20 mmol, 99%). [α]_D ¹⁷ = +7.0 (c = 0.1, EtOH); ¹H NMR (500MHz, D₂O) δ 4.42 (t, J_5a,_5b = J4,sb = 9.2 Hz, IH, H5a), 4.34 (dd, J₄,_5b= 3.6 Hz, J_5a,_5b = 9.2 Hz, IH, H-5b), 4.08 (t, J_3,4 = J₂a,3 = 3.6 Hz, IH, H-3), 3.90 (td, J_3;4 = J_4;5b = 3.6 Hz, J4,_5b = 9.2 Hz, IH, H-4), 3.37 (ddd, Jia,2_b = 8.1 Hz, J_la,_2a = 9.5 Hz, J_la,ib = 10.9 Hz, IH, H-Ia), 3.15 (ddd, Ji_b,_2b = 2.2 Hz, J_lb;2a = 10.0 Hz, J_la,lb = 10.9 Hz, IH, H-Ib), 2.06 (ddd, J_la,2a = 9.5 Hz, Ji_bi2a = 10.0 Hz, J_2a,_2b - 14.2 Hz, IH, H-2a), 1.93 (ddd, Ji_b,_2b = 2.2 Hz, Ji_a,_2b - 8.1 Hz, J_2a,_2b = 14.2 Hz, IH, H-2b); ¹³C NMR (125 MHz, D₂O) δ 69.6 (C3), 64.4 (C4), 64.3 (C5), 43.0 (Cl), 33.7 (C2); IR (film), 3419, 3385, 3047, 2986, 2931, 1730, 1448, 1087 cm^"1. HRMS(ESI) m/z calcd. for [C₆H₉NO₃Na]⁺: 166.0486 obsd.:166.0480.

(2R,3R)-2-(Hydroxymethyl)-3-hydroxypyrrolidine (16). To a solution of carbamate 15 (10 mg, 70 μmol) in EtOH (1 niL) was added NaOH (17 mg, 0.7 mmol). The solution was stirred at reflux for 2 h then cooled and purified directly by ion-exchange chromatography (Dowex H⁺). The product was eluted using 5-15% aqueous NH₃. 16 was isolated as the HCl salt (8.2 mg, 70 μmol, 99%). R/= 0.1 ((DCM/EtOH/MeOH/30% aqueous NH₃, 5/2/2/1, v/v/v/v); [α]_D ¹⁷ - +10.0 (c=0.09, EtOH); ¹H NMR (500MHz, D₂O) δ 4.27 (dt, J_2b,3 = 1.5 Hz, J_2a,3 = J₃,₄ = 4.9 Hz, IH, H3), 3.98 (dd, J_4;5a= 4.9 Hz, J_5%5b = 12.1 Hz, IH, H-5a), 3.83 (dd, J_4,5b = 8.5 Hz, J_5a,5b = 12.1 Hz, IH, H-5b), 3.31 (td, J₃,₄ = J4,_5a = 4.9 Hz, J₄,_5b = 8.5, IH, H-4), 3.25 (ddd, J_la,_2b= 7.6 Hz, J_la,_2a= 9.6 Hz, Ji_a,_lb = 11.6 Hz, IH, H-Ia), 3.21 (ddd, Ji_b,2b = 3.4 Hz, J_lb;2a = 9.9 Hz, J_la,lb = 11.6 Hz, IH, H-Ib), 2.13 (dddd, J_2a,3 = 4.9 Hz, J_2a,la = 9.6 Hz, J_2a,lb = 9.9 Hz, J_2a;2b = 14.1 Hz, IH, H-2a), 2.05 (dddd, J_2b;3 = 1.5 Hz, J_2b,lb = 3.4 Hz, J_2b,i_a = 7.6 Hz, J_2a,2b = 14.1 Hz, IH, H-2b); ¹³C NMR (125 MHz, D₂O) δ 70.8 (C3), 64.1 (C4), 59.0 (C5), 42.9 (C2), 33.3 (Cl); IR (film), 3397, 3364, 2960, 2932, 2874, 1720, 1601, 1168, 1064 cm^"1. HRMS(ESI) m/z calcd. for [C₅Hi₂NO₂J⁺: 118.0868 obsd. : 118.0870.

Example 5

17 18

(2S,3S,4R)-l-Amino-hex-5-ene-2,3,4-triol (18). To a solution of halogenated cyclic acetal 17 (890 mg, 2.93 mmol) in a saturated solution OfNH₄OAc in EtOH (60 mL) was added activated Zn (958 mg, 14.7 mmol), NaCNBH₃ (561 mg, 8.79 mmol) and 30% aqueous NH₃ (23 mL). The mixture was stirred at reflux for 18 h, cooled to room temperature and concentrated under reduced pressure. The residue was redissolved in water and purified directly by ion-exchange chromatography (Dowex H⁺). The product was eluted using 5-15% aqueous NH₃. Alkenylamine 18 was obtained as the HCl salt (501 mg, 2.74 mmol, 93%). ¹H NMR (300 MHz, D₂O) δ 5.71 (ddd, J4,₅

J_5fi._lrms = 17.2 Hz, IH, U-6-trans), 5.14 (d, J_5;6-c/, = 10.6 Hz, IH, H-6-cw), 4.05 (dd, J_3,4 = 6.7, J₄,₅ *= 6.9 Hz, IH, H-4), 3.80 (ddd, J₂₃ = 2.9, Ji_a,₂ = 4.8, J_lba = 7.6 Hz, IH, H-2), 3.36 (dd, J_2>3 = 2.9, J₃,₄= 6.7 Hz, IH, H-3), 2.98 (m, 2H₃ H-Ia and H-Ib); ¹³C NMR (75 MHz, D₂O) δ 135.8 (C5), 118.4 (C6), 74.2 (C3), 73.2 (C4), 67.0 (C2), 42.3 (Cl). HRMS(ESI) m/z calcd. for [C₆H_MNO₃]⁺: 148.0974, obsd.: 148.0977.

Example 6

(2S,3S,4S)-l-Amino-hex-5-ene-2,3,4-triol (22). To a solution of halogenated cyclic acetal 21 (520 mg, 1.71 mmol) in a saturated solution OfNH₄OAc in EtOH (34 mL) was added activated Zn (559 mg, 8.6 mmol), NaCNBH₃ (327 mg, 5.13 mmol) and 30% aqueous NH₃ (14 mL). The mixture was stirred at reflux for 18 h, cooled to room temperature and concentrated under reduced pressure. The residue was redissolved in water and purified directly by ion-exchange chromatography (Dowex H⁺). The product was eluted using 5-15% aqueous NH₃. Alkenylamine 22 was obtained as the HCl salt (215 mg, 1.46 mmol, 86%). ¹H NMR (500 MHz, D₂O) δ 5.93 (ddd, J₄,₅ = 7.0, J_5,6-c/, = 10.5, J_5fi._trms = 17.4 Hz, IH, H-5), 5.35 (dt, J_5,6-/ra,_ω = 17.4,

- Jβ-cisfi-trans = 1.2 Hz IH, H-6-c/tf), 4.12 (dd, J₃₌₄ = 8.0, J_4;5 = 7.1 Hz, IH, H-4), 4.10 (ddd, J_2,3 = 2.4, J_la,2 = 7.5, J_lb>2 = 7.5 Hz, IH, H-2), 3.44 (dd, J_2>3 = 2.4, J_3;4= 8.0 Hz, IH, H-3), 3.13 (m, 2H, H-Ia and H-Ib); ¹³C NMR (75 MHz, D₂O) δ 136.8 (C5), 118.3 (C6), 73.7 (C3), 72.0 (C4), 66.3 (CZ), 42.4 (Cl). HRMS(ESI) m/z calcd. for [C₆H_i4NO₃]⁺: 148.0974, obsd.: 148.0973.

(6S,7R,8S,8aR)-6,7,8-Trihydroxy-hexahydro-oxazolo[3,4-α]pyridin-3-one (23). Alkenylamine 22 hydrochloride (7.9 mg, 0.050 mmol) was subjected to the general iodocyclisation/carbamate formation procedure, as described above for Examples 1 to 4. Carbamate 23 was isolated as an amorphous white powder (8 mg, 0.050 mmol, 99%). ¹H NMR (500MHz, D₂O) δ 4.47 (t, J₅,_6a = J_6a,_6b = 9.0 Hz, IH, H-6a), 4.35 (dd, J_5,6b = 5.0, J_6a,6b = 9.0 Hz, IH, H-6b), 4.05 (ddd, J₄,₅ = 1.9, J₅,_6b = 5.0, J₅,_6a = 9.0 Hz, IH, H-5), 3.96 (dd, J₄,₅ = 1.9, J₃,₄ = 2.3 Hz, IH, H-4), 3.90 (dd, J₁ ^ = 6.1, j_la>lb = 13.1 Hz, IH, H-Ia), 3.79 (ddd, Ji_a,2 = 6.1, J_2,3 = 9.7, Ji_b)2 = 10.5 Hz, IH, H-2), 3.57 (dd, J₃,₄ = 2.3, J₂,₃ = 9.7 Hz, IH, H-3), 2.82 (dd, J_lb;2 = 10.5, J_{1 Mb} = 13.1 Hz, IH, H-Ib); ¹³C NMR (100MHz, D₂O) δ 159.7 (C7), 73.6 (C3), 69.0 (C4), 65.0 (C2), 63.9 (C6), 56.6 (C5), 44.0 (Cl). HRMS(ESI) m/z calcd. for [C₇H₁₁O₅NNa]⁺: 212.0535, obsd. 212.0532.

Example 7

25 26

(3S,4R)-6-Amino-hex-l-ene-3,4-diol (26). To a solution of halogenated cyclic acetal 25 (58 mg, 0.214 mmol) in a saturated solution OfNH₄OAc in EtOH (4.5 mL) was added activated Zn (70.0 mg, 1.1 mmol), NaCNBH₃ (41 mg, 0.64 mmol) and 30% aqueous NH₃ (1.7 mL). The mixture was stirred at reflux for 18 h, cooled to room temperature and concentrated under reduced pressure. The residue was redissolved in H₂O and purified directly by ion-exchange chromatography (Dowex H⁺). The product was eluted using 5-15% aqueous NH₃.

Alkenylamine 26 was obtained as the HCl salt (35 mg, 0.21 mmol, 99%). ¹H NMR (500 MHz, D₂O) δ 5.88 (ddd, J_4>5 = 6.7, J₅,_6-c/, = 10.5, \_Uram = 17.9 Hz, IH, H-5), 5.32 (d, J_5fi._tmιis = 17.9 Hz, IH, n-6'trans), 5.30 (d, J_5;6-c« = 10.5 Hz IH, H-6-cis), 4.06 (dd, J₃,₄ = 4.6, J₄,₅ - 6.7 Hz, IH, H-4), 3.73 (ddd, J_2a>3 = 3.0, J_3>4 = 4.6, J_2b,3 = 9.6 Hz, IH, H-3), 3.13 (m, 2H, H-Ia and H-Ib), 1.93 (m, IH, H-2a), 1.87 (m, IH, H-2b); ¹³C NMR (125 MHz, D₂O) δ 135.5 (C5), 118.0, (C6), 75.4 (C4), 71.6 (C3), 37.1 (Cl), 28.9 (C2). HRMS(ESI) m/z calcd. for [C₆H₁₄NO₂]⁺:132.1025, obsd.:132.1022.

Analysis of the NMR spectra indicated that each of the iodocyclisation/carbamate formation reactions proceeded with diastereoselectivity.

It is not the intention to limit the scope of the invention to the abovementioned examples only. As would be appreciated by a skilled person in the art, many variations are possible without departing from the scope of the invention as set out in the appended claims.

Claims

1. A method for preparing an alkenylamine, or a salt, solvate or hydrate thereof, the method comprising: reacting a halogen-substituted cyclic acetal or a derivative thereof with a reaction metal, a source of ammonia and a hydride source to provide the alkenylamine; optionally converting the alkenylamine into a salt, solvate or hydrate thereof; and optionally isolating the alkenylamine or salt, solvate or hydrate thereof.

2. A method for preparing a compound of Formula I:

or a salt, solvate or hydrate thereof; wherein L is selected from the group consisting of: -C(R¹¹)(R¹²)C(R²¹)(R²²)C(R³¹)(R³²)C(R⁴¹)(R⁴²)C(R⁵¹)(R⁵²)-; -C(R^π)(R¹²)C(R²¹)(R²²)C(R^3I)(R³²)C(R⁴¹)(R⁴²)-; -C(R^π)(R¹²)C(R²¹)(R²²)C(R³¹)(R³²)-; and -C(R¹¹XR^)C(R²¹XR²²)-; wherein R¹¹, R¹², R²¹, R²², R³¹, R³², R⁴¹, R⁴², R⁵¹ and R⁵² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; or R¹¹ and R¹², R²¹ and R²², R³¹ and R³², R⁴¹ and R⁴², and/or R⁵¹ and R⁵², together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or R¹¹ and R²¹, R¹² and R²², R²¹ and R³¹, R²² and R³², R³¹ and R⁴¹, R³² and R⁴², R⁴¹ and R⁵\ and/or R⁴² and R⁵², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl; or R¹¹ and R¹², R²¹ and R²², R³¹ and R³², R⁴¹ and R⁴², and/or R⁵¹ and R⁵² together form a =C(R⁵)₂ , =CR⁶(XR⁷), or =C(XR⁷)₂ group; wherein R¹, R², R ₃ R , R⁵, R⁶ and R⁷ at each occurrence are independently selected from -H, -CN, -R⁸, -C(X)R⁸, -C(X)XR⁸, -C(R⁸)₃, -C(R⁸)₂XR⁸, -CR⁸(XR⁸)₂ and -C(XR⁸)₃; wherein X at each occurrence is independently selected from O, NH, NR⁹ and S; and R⁸ and R⁹ at each occurrence are independently selected from -H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, sulfur, substituted sulfur, silicon, substituted silicon, boron, substituted boron, phosphorus, substituted phosphorus and metal; or R³ and R⁴ together form a =C(R⁵)₂ , =CR⁶(XR⁷), or =C(XR⁷)₂ group; the method comprising: reacting a compound of Formula II:

wherein Z is halo, A is a leaving group, and L is as defined for Formula I; with a reaction metal, a source of ammonia and a hydride source to provide the compound of Formula I; optionally converting the compound of Formula I into a salt, solvate or hydrate thereof; and optionally isolating the compound of Formula I or salt, solvate or hydrate thereof.

3. The method as claimed in claim 2, wherein the compound of Formula II is selected from the group consisting of the compounds of Formula Ha, lib and Hc:

4. The method as claimed in claim 2 or 3, wherein the compound of Formula I has the Formula Ia:

1 1 I T O 1 OO wherein R , R , R and R are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; or R¹¹ and R¹² and/or R²¹ and R²², together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or R¹¹ and R²¹ and/or R¹² and R²², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

5. The method as claimed in claim 4, wherein R and R" are -H, and R and R are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N3; or R¹² and R²², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

6. The method as claimed in claim 4 or 5, wherein R and R are -H, and R and R are each independently selected from the group consisting of -H, -N₃, -OR² and -NR³R⁴, wherein R², R³ and R⁴ at each occurrence are each independently selected from -H, -R⁸, -C(X)R⁸ and -C(X)XR⁸;

7. The method as claimed in any one of claims 4 to 6, wherein R¹¹ and R²¹ are -H, R¹² is -OH; and R²² is selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃.

8. The method as claimed in any one of claims 4 to 7, wherein R^{1 !} and R²¹ are -H, and R¹² and R²² are -OH.

9. The method as claimed in any one of claims 4 to 7, wherein R^{! l}, R²¹ and R²² are -H, and R¹² is -OH.

10. The method as claimed in claim 2 or 3, wherein the compound of Formula I has the Formula Ib:

Ib

wherein R¹¹, R¹², R²¹, R²², R³¹ and R³² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; or R¹¹ and R¹², R²¹ and R²², and/or R³¹ and R³², together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or R¹¹ and R²¹, R¹² and R²², R²¹ and R³¹, and/or R²² and R³², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

11. The method as claimed in claim 10, wherein R¹¹ , R²¹ and R³¹ are -H, and R¹², R²² and R³² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; or R¹² and R²² and/or R²² and R³² together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

12. The method as claimed in claim 10 or 11, wherein R¹¹, R²¹ and R³¹ are -H, and R¹², R²² and R³² are each independently selected from the group consisting of -H, -N₃, -OR² and -NR³R⁴, wherein R², R³ and R⁴ at each occurrence are each independently selected from -H, -R⁸, -C(X)R⁸ and -C(X)XR⁸; X at each occurrence is independently selected from O, NH, NR⁹ and S; and

13. The method as claimed in any one of claims 10 to 12, wherein R¹¹, R²¹ and R³¹ are -H; R¹² is -OH; and R and R are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃.

14. The method as claimed in any one of claims 10 to 13, wherein R¹¹, R²¹ and R³¹ are -H; R¹² and R²² are -OH; and

R³² is selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃.

15. The method as claimed in any one of claims 10 to 14, wherein R¹¹, R²¹ and R³¹ are -H, and R¹², R²² and R³² are -OH.

16. The method as claimed in any one of claims 10 to 14, wherein R¹¹, R²¹, R³¹ and R³² are -H, and R¹² and R²² are -OH.

17. The method as claimed in claim 2 or 3, wherein the compound of Formula I has the Formula ic:

wherein

R¹¹, R¹², R²¹, R²², R³¹, R³², R⁴¹and R⁴² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; or R¹¹ and R¹², R²¹ and R²², R³¹ and R³², and/or R⁴¹ and R⁴², together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or R¹¹ and R²¹, R¹² and R²², R²¹ and R³¹, R²² and R³², R³¹ and R⁴¹, and/or R³² and R⁴², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

18. The method as claimed in claim 17, wherein R¹¹, R²¹, R³¹ and R⁴¹ are -H₅ and R¹², R²², R³² and R⁴² are each independently selected from the group consisting of -H₅ -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; or R¹² and R²² ₅ R²² and R³², and/or R³² and R⁴², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

19. The method as claimed in claim 17 or 18, wherein R¹¹, R²¹, R³¹ and R⁴¹ are -H, and R¹², R²², R³² and R⁴² are each independently selected from the group consisting of -H, -N₃, -OR² and -NR³R⁴, wherein R², R³ and R⁴ at each occurrence are each independently selected from -H₅ -R⁸, -C(X)R⁸ and -C(X)XR⁸; X at each occurrence is independently selected from O, NH₅ NR⁹ and S; and R⁸ and R⁹ at each occurrence are independently selected from -H₅ alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxide, substituted alkoxide, sulfur, substituted sulfur, silicon, substituted silicon, boron, substituted boron, phosphorus, substituted phosphorus and metal.

20. The method as claimed in any one of claims 17 to 19, wherein R¹¹, R²¹, R³¹ and R⁴¹ are -H; - R¹² is -OH; and

R' , R and R are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃.

21. The method as claimed in any one of claims 17 to 20, wherein R¹ \ R²¹, R³¹ and R⁴¹ are -H; R¹² and R²² are -OH; and R³² and R⁴² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃.

22. The method as claimed in any one of claims 17 to 21, wherein R¹¹, R²¹, R³¹ and R⁴¹ are -H; and R¹², R²², R³² and R⁴² are -OH.

23. The method as claimed in any one of claims 2 to 22, wherein the leaving group A is selected from the group consisting of halogen, -OR¹⁰,-NHR¹⁰, -N(R¹⁰)₂, -SR¹⁰, -SOR¹⁰,

-SO₂R¹⁰ and -SeR¹⁰, wherein R¹⁰ is independently selected from -H₅ alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkoxy, substituted alkoxy, acyl, substituted acyl, acetimidoyl, substituted acetimidoyl, amino, substituted amino and halogen.

24. The method as claimed in claim 23, wherein the leaving group A is -OR¹⁰.

25. The method as claimed in claim 24, wherein R¹⁰ is alkyl.

26. The method as claimed in claim 24, wherein R¹⁰ is alkyl, substituted alkyl, alkenyl or aryl.

27. The method as claimed in claim 24 or 26, wherein R¹⁰ is selected from the group consisting of methyl, ethyl, propyl, butyl, allyl, phenyl and benzyl.

28. The method as claimed in any one of claims 24 to 27, wherein R¹⁰ is methyl.

29. The method as claimed in any one of claims 2 to 28, wherein Z is selected from the group consisting of -I, -Br and -Cl.

30. The method as claimed in any one of claims 2 to 29, wherein Z is -I.

31. The method as claimed in any one of claims 1 to 30, wherein the reaction metal is selected from the group consisting of lithium, sodium, potassium, zinc, barium, magnesium, titanium, zirconium, indium, and mixtures of any two or more thereof.

32. The method as claimed in any one of claims 1 to 31, wherein the reaction metal is zinc.

33. The method as claimed in any one of claims 1 to 30, wherein the reaction metal is an alloy.

34. The method as claimed in claim 33, wherein the alloy is an amalgam.

35. The method as claimed in claim 34, wherein the amalgam is Zn(Hg) or Na(Hg).

36. The method as claimed in any one of claims 1 to 35, wherein the source of ammonia is NH₃.

37. The method as claimed in any one of claims 1 to 35, wherein the source of ammonia is an ammonium salt.

38. The method as claimed in any one of claims 1 to 35, wherein the source of ammonia is a mixture of NH₃ and one or more ammonium salt.

39. The method as claimed in claim 36 or 38, wherein the NH₃ is ammonia gas, a solution of ammonia or a mixture thereof.

40. The method as claimed in claim 39, wherein the solution of ammonia is aqueous ammonia or a solution of ammonia in an organic solvent.

41. The method as claimed in claim 40, wherein the organic solvent is an alcohol.

42. The method as claimed in claim 41 , wherein the alcohol is methanol or ethanol.

43. The method as claimed in claim 37 or 38, wherein the ammonium salt is selected from the group consisting OfNH₄OH, NH₄Cl, NH₄OAc, NH₄HCO₂, NH₄HSO₄, (NH₄)₂SO₄, NH₄HCO₃, (NH₄)₂CO₃, and mixtures of any two or more thereof.

44. The method as claimed in any one of claims 37, 38 and 43, wherein the ammonium salt is NH₄OAc.

45. The method as claimed in any one of claims 1 to 44, wherein the hydride source is a metal hydride.

46. The method as claimed in claim 45, wherein the metal hydride is lithium aluminium hydride or diisobutylaluminium hydride.

47. The method as claimed in any one of claims 1 to 44, wherein the hydride source is a borohydride.

48. The method as claimed in claim 47, wherein the borohydride is selected from the group consisting OfNaBH₄, NaBH₃CN, LiBH₃CN, NaBH₃CN-ZnCl₂, NaBH₃CN-Ti(OZPr)₄, NaBH₃CN-Mg(C10₄)₂, (/7-Bu)₄NBH₃ CN, NaBH(OAc)₃, NaBH₄-NiCl₂, NaBH₄-ZnCl₂,

NaBH₄-ZrCl₄, Ti(OzPr)₄-NaBH₄, and NaBH₄-H₂SO₄.

49. The method as claimed in claim 47 or 48, wherein the borohydride is sodium cyanoborohydride (NaBH₃CN) or sodium triacetoxyborohydride (NaBH(OAc)₃).

50. The method as claimed in any one of claims 47 to 49, wherein the borohydride is sodium cyanoborohydride (NaBH₃CN).

51. The method as claimed in claim 47 or 48, wherein the borohydride is NaBH₃CN-ZnCl₂, ■ NaBH₃CN-Ti(OzPr)₄, NaBH₄-ZnCl₂ and NaBH₄-ZrCl₄, Ti(OzPr)₄-NaBH₄.

52. The method as claimed in claim 47, wherein the borohydride is a borohydride exchange resin or sodium borohydride on wet clay.

53. The method as claimed in any one of claims 1 to 44, wherein the hydride source is sodium borohydride activated by boric acid.

54. The method as claimed in any one of claims 1 to 44, wherein the hydride source is selected from the group consisting of nickel boride, Zn(BH₄)₂, Zn(BEU)₂-ZnCl₂, Zn(BH₄)₂-Si0₂, Zn-AcOH, polymethylhydrosiloxane (PMHS)-Ti(OZPr)₄, PMHS-ZnCl₂, PMHS-BuSn(OCOR)₃, Et₃SiH-CF₃CO₂H, (PhMe₂)SiH-(C₆F₆)₃, Cl₃SiH-DMF, PhSiH₃-Bu₂SnCl₂, ^-Bu₃SnH-DMF or HMPA, ^-Bu₃SnH-SiO₂ and ^-Bu₂SnIH or H-Bu₂SnClH.

55. The method as claimed in any one of claims 1 to 44, wherein the hydride source is a borane reducing agent.

56. The method as claimed in claim 55, wherein the borane reducing agent is pyridine-borane; picoline-borane; diborane-MeOH; or decaborane.

57. The method as claimed in any one of claims 2 to 56, wherein the compound of Formula II is enantiopure and the resulting compound of Formula I is chiral.

58. A method for preparing a cyclic carbamate or cyclic dithiocarbamate, or a salt, solvate or hydrate thereof, the method comprising: reacting an alkenylamine with a halogen source, a base and a source of carbonate or a source of carbon dioxide or a source of carbon disulfide to provide the cyclic carbamate or cyclic dithiocarbamate; optionally converting the cyclic carbamate or cyclic dithiocarbamate into a salt, solvate or hydrate thereof; and optionally isolating the cyclic carbamate or cyclic dithiocarbamate or salt, solvate or hydrate thereof.

59. A method for preparing a compound of Formula III:

III or a salt, solvate or hydrate thereof; wherein Y is O or S;

L is selected from the group consisting of:

-C(Rⁿ)(R¹²)C(R²¹)(R²²)C(R³¹)(R³²)C(R⁴¹)(R⁴²)-;

-C(Rⁿ)(R¹²)C(R²¹)(R²²)C(R³¹)(R³²)-; and i l h > 12- 2K 22

-C(R¹0(R¹OC(R^)(R )-; wherein R¹¹, R¹², R²¹, R²², R³¹, R³², R⁴¹, R⁴², R⁵¹ and R⁵² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; or R¹¹ and R¹², R²¹ and R²², R³¹ and R³², R⁴¹ and R⁴², and/or R⁵¹ and R⁵², together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or R¹¹ and R²¹, R¹² and R²², R²¹ and R³¹, R²² and R³², R³¹ and R⁴¹, R³² and R⁴², R⁴¹ and R⁵¹, and/or R⁴² and R⁵², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl; or R¹¹ and R¹², R²¹ and R²², R³¹ and R³², R⁴¹ and R⁴², and/or R⁵¹ and R⁵² together form a =C(R⁵)₂ , =CR⁶(XR⁷), or =C(XR⁷)₂ group; wherein R¹, R², R³, R⁴, R⁵, R⁶ and R⁷ at each occurrence are independently selected from -H, -CN, -R⁸, -C(X)R⁸, -C(X)XR⁸, -C(R⁸)₃, -C(R⁸)₂XR⁸, -CR⁸(XR⁸)₂ and -C(XR⁸)₃; wherein X at each occurrence is independently selected from O, NH, NR⁹ and S; and

R⁸ and R⁹ at each occurrence are independently selected from -H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, sulfur, substituted sulfur, silicon, substituted silicon, boron, substituted boron, phosphorus, substituted phosphorus and metal; or R³ and R⁴ together form a =C(R⁵)₂ , =CR⁶(XR⁷), or =C(XR⁷)₂ group; the method comprising: reacting a compound of Formula I₅ as defined in claim 2, with a halogen source, a base and a source of carbonate or a source of carbon dioxide or a source of carbon disulfide to provide the compound of Formula III; optionally converting the compound of Formula III into a salt, solvate or hydrate thereof; and optionally isolating the compound of Formula III or salt, solvate or hydrate thereof.

60. The method as claimed in claim 59, wherein the compound of Formula III is selected from the group consisting of the compounds of Formula Ilia, IHb and IHc:

61. The method as claimed in claim 59, wherein the compound of Formula III is selected from the group consisting of the compounds of Formula Ilia', IHb' and IHc' :

62. The method as claimed in claim 59 or 60, wherein the compound of Formula III has the Formula Ilia:

wherein Y is O or S;

1 1 I O 01 OO

R ₅ R ₅ R and R are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; or R¹¹ and R¹² and/or R²¹ and R²², together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or R¹¹ and R^2! and/or R¹² and R²², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

63. The method as claimed in claim 62, wherein R and R are -H, and R and R are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; or R¹² and R²², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

64. The method as claimed in claim 62 or 63, wherein R¹¹ and R²¹ are -H, and R¹² and R²² are each independently selected from the group consisting of -H, -N₃, -OR² and -NR³R⁴, wherein R², R³ and R⁴ at each occurrence are each independently selected from -H, -R⁸, -C(X)R⁸ and -C(X)XR⁸; X at each occurrence is independently selected from O, NH, NR⁹ and S; and

65. The method as claimed in any one of claims 62 to 64, wherein R¹¹ and R²¹ are -H; R¹² is -OH; and

R²² is selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃.

66. The method as claimed in any one of claims 62 to 65, wherein R¹¹ and R²¹ are -H; and R¹² and R²² are -OH.

67. The method as claimed in any one of claims 62 to 65, wherein R¹¹, R²¹ and R²² are -H; and R¹² is -OH.

68. The method as claimed in any one of claims 62 to 67, wherein Y is O.

69. The method as claimed in claim 59 or 60, wherein the compound of Formula III has the Formula IHb:

wherein Y is O or S; R , R , R , R , R and R are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; or R¹¹ and R¹², R²¹ and R²², and/or R³¹ and R³², together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or R¹¹ and R²¹, R¹² and R²², R²¹ and R³¹, and/or R²² and R³², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

70. The method as claimed in claim 69, wherein R¹¹, R²¹ and R³¹ are -H, and R¹², R²² and R³² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; or R¹² and R²² and/or R²² and R³² together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

71. The method as claimed in claim 69 or 70, wherein R¹¹, R²¹ and R³¹ are -H, and R¹², R²² and R are each independently selected from the group consisting of -H, -N₃, -OR aanndd --NNRR³³RR⁴⁴,, wwhheerreeiinn RR²²,, RR³³ aanndd RR⁴⁴ aatt ee:ach occurrence are each independently selected from -H, -R⁸, -C(X)R⁸ and -C(X)XR⁸; X at each occurrence is independently selected from O, NH, NR⁹ and S; and

72. The method as claimed in any one of claims 69 to 71, wherein R¹¹, R²¹ and R³¹ are -H; R¹² is -OH; and

R²² and R³² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃.

73. The method as claimed in any one of claims 69 to 72, wherein R¹¹, R²¹ and R³¹ are -H;

■ R¹² and R²² are -OH; and R³² is selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃.

74. The method as claimed in any one of claims 69 to 73, wherein R 11 , rR>21 „ a„nd^■, „ R31 are -H; and R¹², R²² and R³² are -OH.

75. The method as claimed in any one of claims 69 to 73, wherein R¹¹, R²¹, R³¹ and R³² are -H; and R¹² and R²² are -OH.

76. The method as claimed in any one of claims 69 to 75, wherein Y is O.

77. The method as claimed in claim 59 or 60, wherein the compound of Formula III has the Formula IHc:

wherein Y is O or S; R¹¹, R¹², R²¹, R²², R³¹, R³², R⁴¹ and R⁴² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; or R¹¹ and R¹², R²¹ and R²², R³¹ and R³², and/or R⁴¹ and R⁴², together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or R¹¹ and R²¹, R¹² and R²², R²¹ and R³¹, R²² and R³², R³¹ and R⁴¹, and/or R³² and R⁴², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

78. The method as claimed in claim 77, wherein R¹ \ R²¹, R³¹ and R⁴¹ are -H, and R¹², R²², R³² and R⁴² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; or R¹² and R²², R²² and R³², and/or R³² and R⁴², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

79. The method as claimed in claim 77 or 78, wherein R¹¹, R²¹, R³¹ and R⁴¹ are -H, and R¹², R²², R³² and R⁴² are each independently selected from the group consisting of -H, -N₃, -OR² and -NR³R⁴, wherein R², R³ and R⁴ at each occurrence are each independently selected from -H, -R⁸, -C(X)R⁸ and -C(X)XR⁸; X at each occurrence is independently selected from O, NH, NR⁹ and S; and R⁸ and R⁹ at each occurrence are independently selected from -H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxide, substituted alkoxide, sulfur, substituted sulfur, silicon, substituted silicon, boron, substituted boron, phosphorus, substituted phosphorus and metal.

80. The method as claimed in any one of claims 77 to 79, wherein R¹¹, R²¹, R³¹ and R⁴¹ are -H; R¹² is -OH; and

R²², R³² and R⁴² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃.

81. The method as claimed in any one of claims 77 to 80, wherein Rⁿ, R²¹, R³¹ and R⁴¹ are -H; R¹² and R²² are -OH; and

R³² and R⁴² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃.

82. The method as claimed in any one of claims 77 to 81, wherein R¹¹, R²¹, R³¹ and R⁴¹ are -H; and R¹², R²², R³² and R⁴² are -OH.

83. The method as claimed in any one of claims 77 to 82, wherein Y is O.

84. The method as claimed in claim 59, wherein the compound of Formula I is obtained by a method as claimed in claim 2.

85. The method as claimed in any one of claims 58 to 84, wherein the halogen source is selected from the group consisting of NIS, NBS, NCS, I₂, Br₂, Cl₂, and mixtures of any two or more thereof.

86. The method as claimed in any one of claims 58 to 85, wherein the halogen source is I₂.

87. The method as claimed in any one of claims 58 to 86, wherein the source of carbonate is selected from the group consisting OfLiHCO₃, Li₂CO₃, NaHCO₃, Na₂CO₃, KHCO₃, K₂CO₃, and mixtures of any two or more thereof.

88. The method as claimed in any one of claims 58 to 87, wherein the source of carbonate is NaHCO₃.

89. The method as claimed in any one of claims 58 to 86, wherein the source of carbon dioxide is selected from the group consisting of carbon dioxide gas, liquid carbon dioxide, solid carbon dioxide, and mixtures of any two or more thereof.

90. The method as claimed in any one of claims 58 to 60, 62 to 67, 69 to 75, 77 to 82, and 84 to 86, wherein the source of carbon disulfide is CS₂.

91. The method as claimed in any one of claims 59 to 90, wherein the compound of Formula I is enantiopure and the resulting compound of Formula III is chiral.

92. A method for preparing a cyclic carbamate or cyclic dithiocarbamate, or a salt, solvate or hydrate thereof, the method comprising: reacting a halogen-substituted cyclic acetal or a derivative thereof with a reaction metal, a source of ammonia and a hydride source to provide an alkenylamine; reacting the alkenylamine with a halogen source, a base and a source of carbonate or a source of carbon dioxide or a source of carbon disulfide to provide the cyclic carbamate or cyclic dithiocarbamate; optionally converting the cyclic carbamate or cyclic dithiocarbamate into a salt, solvate or hydrate thereof; and optionally isolating the cyclic carbamate or cyclic dithiocarbamate or salt, solvate or hydrate thereof.

93. The method as claimed in claim 92, wherein the halogen-substituted cyclic acetal or derivative thereof is enantiopure and the reactions are stereo- and regioselective, such that the resulting cyclic carbamate or cyclic dithiocarbamate is chiral.

94. The method as claimed in claim 92 or 93, wherein the method is for preparing a cyclic carbamate, or a salt, solvate or hydrate thereof and wherein the method comprises: reacting a halogen-substituted cyclic acetal or a derivative thereof with a reaction metal, a source of ammonia and a hydride source to provide an alkenylamine; reacting the alkenylamine with a halogen source, a base and a source of carbonate or a source of carbon dioxide to provide the cyclic carbamate; optionally converting the cyclic carbamate into a salt, solvate or hydrate thereof; and optionally isolating the cyclic carbamate or salt, solvate or hydrate thereof.

95. A method for preparing a 1 ,2-aminoalcohol or 1,2-aminothiol, or a salt, solvate or hydrate thereof, the method comprising: reacting an alkenylamine with a halogen source, a base and a source of carbonate or a source of carbon dioxide or a source of carbon disulfide to provide a cyclic carbamate or cyclic dithiocarbamate; deprotecting the cyclic carbamate or cyclic dithiocarbamate to provide the 1,2-aminoalcohol or 1,2-aminothiol; optionally converting the 1,2-aminoalcohol or 1,2-aminothiol into a salt, solvate or hydrate thereof; and optionally isolating the 1,2-aminoalcohol or 1,2-aminothiol or salt, solvate or hydrate thereof.

96. The method as claimed in claim 95, wherein the alkenylamine is enantiopure and the reactions are stereo- and regioselective, such that the resulting 1,2-aminoalcohol or 1,2-aminothiol is chiral.

97. A method for preparing a compound of Formula IV:

IV or a salt, solvate or hydrate thereof; wherein Y is O or S;

L is selected from the group consisting of:

-C(R^π)(R¹²)C(R²¹)(R²²)C(R³¹)(R³²)C(R⁴¹)(R⁴²)C(R⁵¹)(R⁵²)-; -C(R¹¹)(R¹²)C(R²¹)(R²²)C(R^3I)(R³²)C(R⁴¹)(R⁴²)-;

-C(R^π)(R¹²)C(R²¹)(R²²)C(R³¹)(R³²)-; and

=C(R⁵)₂ , =CR⁶(XR⁷), or =C(XR⁷)₂ group; wherein R¹, R², R³, R⁴, R⁵, R⁶ and R⁷ at each occurrence are independently selected from -H, -CN, -R⁸, -C(X)R⁸, -C(X)XR⁸, -C(R⁸)₃, -C(R⁸)₂XR⁸, -CR⁸(XR⁸)₂ and -C(XR⁸)₃; wherein X at each occurrence is independently selected from O, NH, NR⁹ and S; and

R and R at each occurrence are independently selected from -H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, sulfur, substituted sulfur, silicon, substituted silicon, boron, substituted boron, phosphorus, substituted phosphorus and metal; or R³ and R⁴ together form a =C(R⁵)₂ , -CR⁶(XR⁷), or =C(XR⁷)₂ group; the method comprising: reacting a compound of Formula I, as defined in claim 2, with a halogen source, a base and a source of carbonate or a source of carbon dioxide or a source of carbon disulfide to provide a compound of Formula III, as defined in claim 59; deprotecting the compound of Formula III to provide the compound of Formula IV; optionally converting the compound of Formula IV into a salt, solvate or hydrate thereof; and optionally isolating the compound of Formula IV or salt, solvate or hydrate thereof.

98. The method as claimed in claim 97, wherein the compound of Formula IV is selected from the group consisting of the compounds of Formula IVa, IVb and IVc:

99. The method as claimed in claim 97, wherein the compound of Formula IV is selected from the group consisting of the compounds of Formula IVa', IVb' and IVc':

311 IVc'.

100. The method as claimed in claim 97 or 98, wherein the compound of Formula IV has the Formula IVa:

wherein Y is O or S;

R ₅ R ₅ R and R are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; or R and R and/or R and R , together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or R and R and/or R and R , together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

101. The method as claimed in claim 100, wherein R¹¹ and R²¹ are -H, and R¹² and R²² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; or R¹² and R²², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

102. The method as claimed in claim 100 or 101, wherein R¹¹ and R²¹ are -H, and R¹² and R²² are each independently selected from the group consisting of -H, -N₃, -OR² and -NR³R⁴, wherein R², R³ and R⁴ at each occurrence are each independently selected from -H, -R⁸, -C(X)R⁸ and -C(X)XR⁸; X at each occurrence is independently selected from O, NH, NR⁹ and S; and

103. The method as claimed in any one of claims 100 to 102, wherein R and R are -H; R¹² is -OH; and

104. The method as claimed in any one of claims 100 to 103, wherein R ^[ and R²¹ are -H; and R¹² and R²² are -OH.

105. The method as claimed in any one of claims 100 to 103, wherein Rⁿ, R²¹ and R²² are -H; and R¹² is -OH.

106. The method as claimed in any one of claims 100 to 105, wherein Y is O.

107. The method as claimed in claim 97 or 98, wherein the compound of Formula IV has the Formula IVb:

IVb wherein Y is O or S;

R¹¹, R¹², R²¹, R²², R³¹ and R³² are each independently selected from the group consisting of-H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; or R¹¹ and R¹², R²¹ and R²², and/or R³¹ and R³², together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or R¹¹ and R²¹, R¹² and R²², R²¹ and R³¹, and/or R²² and R³², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

108. The method as claimed in claim 107, wherein R¹¹, R²¹ and R³¹ are -H, and R¹², R²² and R³² are each independently selected from the group consisting of-H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; or R and R and/or R and R together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

109. The method as claimed in claim 107 or 108, wherein R¹¹, R²¹ and R³¹ are -H, and R¹², R²² and R³² are each independently selected from the group consisting of -H, -N₃, -OR² and -NR³R⁴, wherein R², R³ and R⁴ at each occurrence are each independently selected from -H₅ -R⁸, -C(X)R⁸ and -C(X)XR⁸;

X at each occurrence is independently selected from O, NH, NR⁹ and S; and R and R at each occurrence are independently selected from -H₅ alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxide, substituted alkoxide, sulfur, substituted sulfur, silicon, substituted silicon, boron, substituted boron, phosphorus, substituted phosphorus and metal.

110. The method as claimed in any one of claims 107 to 109, wherein R¹¹, R²¹ and R³¹ are -H; R¹² is -OH; and

R²² and R³² are each independently selected from the group consisting of-H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃.

111. The method as claimed in any one of claims 107 to 110, wherein R¹¹, R²¹ and R³¹ are -H; R¹² and R²² are -OH; and

R³² is selected from the group consisting of -H₅ -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃.

112. The method as claimed in any one of claims 107 to 111, wherein R¹¹, R²¹ and R³¹ are -H; and R¹², R²² and R³² are -OH.

113. The method as claimed in any one of claims 107 to 111, wherein R¹¹, R²¹, R³¹ and R³² are -H; and R¹² and R²² are -OH.

114. The method as claimed in any one of claims 107 to 113, wherein Y is O.

115. The method as claimed in claim 97 or 98, wherein the compound of Formula IV has the Formula IVc:

wherein Y is O or S;

R¹¹, R¹², R²¹, R²², R^{3 i}, R³², R^4Iand R⁴² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; or R¹¹ and R¹², R²¹ and R²², R³¹ and R³², and/or R⁴¹ and R⁴², together with the carbon atom to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl; or R¹¹ and R²¹, R¹² and R²², R²¹ and R³¹, R²² and R³², R³¹ and R⁴¹, and/or R³² and R⁴², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

116. The method as claimed in claim 115, wherein R¹¹, R²¹, R³¹ and R⁴¹ are -H, and R¹², R²², R³² and R⁴² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃; or R¹² and R²², R²² and R³², and/or R³² and R⁴², together with the carbon atoms to which they are attached, form a cyclic group selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl and substituted heterocyclyl.

117. The method as claimed in claim 115 or 116, wherein R¹¹, R²¹, R³¹ and R⁴¹ are -H, and R¹²,

are each independently selected from the group consisting of -H, -N₃, -OR² and -NR³R⁴, wherein R², R³ and R⁴ at each occurrence are each independently selected from -H, -R⁸, -C(X)R⁸ and -C(X)XR⁸; X at each occurrence is independently selected from O, NH, NR⁹ and S; and R^s and R⁹ at each occurrence are independently selected from -H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxide, substituted alkoxide, sulfur, substituted sulfur, silicon, substituted silicon, boron, substituted boron, phosphorus, substituted phosphorus and metal.

118. The method as claimed in any one of claims 115 to 117, wherein R¹¹, R²¹, R³¹ and R⁴¹ are -H;

R¹² is -OH; and

R , R³ and R ² are each independently selected from the group consisting of -H, -R¹, -OR², -SR², -NR³R⁴, -NO₂ and -N₃.

119. The method as claimed in any one of claims 115 to 118, wherein R¹¹, R²¹, R³¹ and R⁴¹ are -H;

R¹² and R²² are -OH; and

120. The method as claimed in any one of claims 115 to 119, wherein R¹¹, R²¹, R³¹ and R⁴¹ are -H; and R¹², R²², R³² and R⁴² are -OH.

121. The method as claimed in any one of claims 115 to 120, wherein Y is O.

122. The method as claimed in any one of claims 95 to 121, wherein the deprotection reaction is carried out under alkaline conditions, under acidic conditions, or with a peroxide.

123. The method as claimed in claim 122, wherein the deprotection reaction is carried out under alkaline conditions with sodium hydroxide in ethanol at reflux temperature.

124. The method as claimed in claim 122, wherein the deprotection reaction is carried out under acidic conditions with 6N aqueous HCl at reflux temperature.

125. The method as claimed in claim 122, wherein the peroxide is LiOOH or H₂O₂ZLiOH.

126. The method as claimed in any one of claims 97 to 125, wherein the method further comprises reacting a compound of Formula II, as defined in claim 2, with a reaction metal, a source of ammonia and a hydride source to provide the compound of Formula I, as defined in claim 2.

127. The method as claimed in any one of claims 97 to 126, wherein the compound of Formula I is enantiopure and the resulting compound of Formula IV is chiral.

128. A method for preparing a 1,2-aminoalcohol or 1 ,2-aminothiol, or a salt, solvate or hydrate thereof, the method comprising: reacting a halogen-substituted cyclic acetal or a derivative thereof with a reaction metal, a source of ammonia and a hydride source to provide an alkenylamine; reacting the alkenylamine with a halogen source, a base and a source of carbonate or a source of carbon dioxide or a source of carbon disulfide to provide a cyclic carbamate or cyclic dithiocarbamate; deprotecting the cyclic carbamate or cyclic dithiocarbamate to provide the

1,2-aminoalcohol or 1 ,2-aminothiol; optionally converting the 1,2-aminoalcohol or 1 ,2-aminothiol into a salt, solvate or hydrate thereof; and optionally isolating the 1,2-aminoalcohol or 1 ,2-aminothiol or salt, solvate or hydrate thereof.

129. The method as claimed in claim 128, wherein the halogen-substituted cyclic acetal or derivative thereof is enantiopure and the reactions are stereo- and regioselective, such that the resulting 1,2-aminoalcohol or 1 ,2-aminothiol is chiral.

130. The method as claimed in claim 128 or 129, wherein the method is for preparing a 1,2-aminoalcohol, or a salt, solvate or hydrate thereof and wherein the method comprises: reacting a halogen-substituted cyclic acetal or a derivative thereof with a reaction metal, a source of ammonia and a hydride source to provide an alkenylamine; reacting the alkenylamine with a halogen source, a base and a source of carbonate or a source of carbon dioxide to provide a cyclic carbamate; deprotecting the cyclic carbamate to provide the 1,2-aminoalcohol; optionally converting the 1,2-aminoalcohol into a salt, solvate or hydrate thereof; and optionally isolating the 1,2-aminoalcohol or salt, solvate or hydrate thereof.

131. An alkenylamine, or a salt, solvate or hydrate thereof, when prepared by a method as claimed in any one of claims 1 and 31 to 57.

132. A compound of Formula II, as defined in claim 2, or a salt, solvate or hydrate thereof, when prepared by a method as claimed in any one of claims 2 to 57.

133. A cyclic carbamate, or a salt, solvate or hydrate thereof, when prepared by a method as claimed in any one of claims 58, 85 to 89 and 92 to 94.

134. A cyclic dithiocarbamate, or a salt, solvate or hydrate thereof, when prepared by a method as claimed in any one of claims 58, 85, 86, 90, 92 and 93.

135. A compound of Formula III, as defined in claim 59, or a salt, solvate or hydrate thereof, when prepared by a method as claimed in any one of claims 59 to 91.

136. A l ,2-aminoalcohol, or a salt, solvate or hydrate thereof, when prepared by a method as claimed in any one of claims 95, 96, 122 to 125 and 128 to 130.

137. A 1,2-aminothiol, or a salt, solvate or hydrate thereof, when prepared by a method as claimed in any one of claims 95, 96, 122 to 125, 128 and 129.

138. A compound of Formula IV, as defined in claim 97, or a salt, solvate or hydrate thereof, when prepared by a method as claimed in any one of claims 97 to 127.