WO2006082054A1 - 1,4-bis-diphosphines, 1,4-bis-diphosphites and 1,4-bis- diphosphonites from optically active (z)-olefines as chiral ligands - Google Patents

1,4-bis-diphosphines, 1,4-bis-diphosphites and 1,4-bis- diphosphonites from optically active (z)-olefines as chiral ligands Download PDF

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WO2006082054A1
WO2006082054A1 PCT/EP2006/000914 EP2006000914W WO2006082054A1 WO 2006082054 A1 WO2006082054 A1 WO 2006082054A1 EP 2006000914 W EP2006000914 W EP 2006000914W WO 2006082054 A1 WO2006082054 A1 WO 2006082054A1
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branched
linear
cyclic alkyl
phenyl
cyclic
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Edoardo Cesarotti
Isabella Rimoldi
Paola Spalluto
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Universita' Degli Studi Di Milano
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Definitions

  • 1,4-BIS-DIPHOSPHINES 1,4-BIS-DIPHOSPHITES AND 1,4-BIS- DIPHOSPHONITES FROM OPTICALLY ACTIVE (Z)-OLEFINES AS CHIRAL LIGANDS
  • Object of the present invention are chiral diphosphines, diphosphinites, diphosphites and diphosphonites, complexes between said diphosphines, diphosphinites, diphosphites and diphosphonites and transition metals, and their utilization as chiral catalysts in stereoselective reactions, such as, for instance, diastero- and enantioselective reduction reactions in general, asymmetric hydroformylations in general, asymmetric hydrocyanations in general.
  • Another object of the present invention is a process for the preparation of said chiral diphosphines, diphosphinites, diphosphites and diphosphonites, as well as a process for the preparation of said chiral complexes and their utilization as catalysts in diastero- and enantioselective reactions.
  • Another object of the present invention is stereoselective processes, in particular diastero- and enantioselective reductions in general, which utilize said chiral catalysts.
  • stereoselective reactions in particular the reaction of stereocontrolled reduction, such as, for instance, diastero- and enantioselective hydrogenations, are of great importance and have been studied for a long time; in fact, such reactions lead directly to the formations of optically active compounds which would be obtainable otherwise only as racemates, with the ensuing need of subsequent separation of the enantiomers.
  • the asymmetric stereocontrolled catalysis and in particular the stereocontrolled reduction reactions realized by means of chiral catalysts allow to obtain the optically active reaction products, often also with good enantiomeric excesses
  • H.U. Blaser Asymmetric catalysis on industrial scale, E. SHMIDT Eds. ,2004
  • M. Beller C. BoIm, Transition metals for organic synthesis: Building Blocks and Fine Chemicals, J. Wiley and Sons Ltd., England, vol 1 e 2, 1998
  • R. Noyori Asymmetric Catalysis in Organic Synthesis, Wiley, New York, 1994.
  • asymmetric catalytic reactions are those based on the formation of C-C bonds together with the concomitant formation of one or more stereogenic centre like the asymmetric hydroformylation of defines, the asymmetric allylic substitution, the hydrocyanation of olefins and aldehydes.
  • chiral phosphines which can act as ligands and form chiral complexes with transition metals, such as, for instance, Ruthenium (Ru), Rhodium (Rh), Palladium (Pd), Iridium (Ir) and Platinum (Pt).
  • transition metals such as, for instance, Ruthenium (Ru), Rhodium (Rh), Palladium (Pd), Iridium (Ir) and Platinum (Pt).
  • the chirality can be generated from the presence of stereogenic sp 3 carbon or sp 3 phosphorus atoms, like in ligand 1[J. C. Poulin, T.P. Dang, H.B. Kagan, Organomet. Chem., 1975, 84, 87], 2 [J. Bakos, I. Toth, L. Marko, J. Org. Chem., 1981, 46, 5427], 3 [(a) W.S. Knowles, MJ. Sabacky, J. Chem. Soc, Chem. Commun., 1971, 481; (b) W.S. Knowles, M.J. Sabacky, B.D. Veneyard, J. WeinKauff, J. Am. Chem. Soc, 1975, 97, 2567], 4 and 9 [P.A. MacNeil, N.K. Roberts, B. Bosnich, J. Am. Chem. Soc, 1981, 103, 2273].
  • the chirality can be due to the presence of an atropisomeric biaryl system, i.e. a system in which the rotation around a single bond connecting two aryl groups is prevented; diphosphines of this type are for instance ligands 5 [a) A. Miyashita, H. Takaya, Tetrahedron, 1984, 40, 1245. (b) A. Miyashita, A. Yasuda, H. Takaya, K. Toriumi, T. Ito, T. Souchi, R. Noyori, J. Am. Chem. Soc, 1980, 202, 7933] and 7 [(a) T. Benincori, E. Brenna, F. Sannicolo, L. Trimarco, P.
  • the ligands of type 6 are based on the planar chirality of ⁇ 5 coordinated 1 ,2-disubstituted cyclopentadienyl ring.
  • the ligands of type 8 are an example of diphosphine in which are contemporary present both the chirality due to a stereogenic sp 3 centre and the atropoisomeric one [E. Cesarotti, S. Araneo, I. Rimoldi, S. Tassi, J. MoI. Catal. A: Chem., 2003, 204, 211].
  • the majority of these ligands present stereogenic sp 3 carbon atoms and structural analogies with DIOP (1 of fig. 1). Further to the chelation with metals, these ligands generate seven-membered chelate rings; there are less examples of chelating diphosphines such as CHIRAPHOS (2 of fig. 1), which form five-membered rings upon chelation. Both these kinds of ligands, the second ones into a minor extent, are characterized by a more or less conformational flexibility.
  • Rh(I)-complexes derived from these ligands, have been successfully applied in the stereoselective hydrogenation of olefinic double bonds and in the preparation of N-substituted ⁇ -aminoacids.
  • W.S. Knowles Asymmetric Hydrogenation- The Monsanto L-Dopa Process, in Asymmetric Catalysis on Industrial Scale, H.U.Blaser and E.Schmidt, eds editors, 2004, Wiley, pp. 23-38; R. Selke, The Other L-Dopa Process, ibidem, pp. 39-54].
  • Rh(I)-complexes usually gives disappointing low enantioselectivities in the reduction of carbonyl groups and imines.
  • Rh(II)-complexes which are the catalyst of choice in the reduction of carbonyl group and Ir(I)-complexes which give catalyst able to reduce imines to amines are almost ineffective and/or give extremely low enantioselectivities when the metals are coordinated to the aforementioned ligands.
  • the catalysts for the stereocontrolled reduction such as the diastero- and enantioselective hydrogenations of carbonyl groups, which allow to obtain the best diastereomeric and enantiomeric excesses of secondary alcohols, are those constituted by complexes between transition metals and chiral atropoisomeric diphosphine, and in particular complexes between Ru(II) and BINAP or Ru(II) and BITIOP, ligands 5 and 7 (fig. 1).
  • the main feature of the atropisomeric diphosphines is a seven-membered chelate ring characterized by a rather high conformational rigidity.
  • the main problem is that of the synthesis of the chiral diphosphine which acts as ligand.
  • the process of synthesis of the chiral diphosphine is rather complicated, as it involves numerous steps; besides, the diphosphine which is obtained as a racemate needs a laborious resolution process, with low yields and very high costs.
  • the chiral catalyst obtained by formation of a complex between the chiral diphosphine and a transition metal may be very expensive.
  • An aim of the present invention is to provide chiral diphosphines, diphosphinites, diphosphites and diphosphonites suitable for acting as ligands for transition metals through the formation of particularly stable coordination bonds.
  • An aim of the invention is to provide chiral diphosphines, diphosphates, diphosphates and diphosphonites that gather the conformational rigidity of an atropoisomeric ligands with the possibility to easily modulate the steric properties by the modification of the substituents on the stereogenic atoms.
  • Another aim of the invention is to provide chiral diphosphines, diphosphinites, diphosphites and diphosphonites such as to be obtainable more easily from the synthetic point of view compared to the known art.
  • Still another aim of the invention is to provide a process for the preparation of chiral diphosphines, diphosphinites, diphosphites and diphosphonites suitable to act as ligands for transition metals, consisting of simple steps, having contained costs and being industrially applicable.
  • Still a further aim of the present invention is to provide a new chiral catalyst to be used in stereocontrolled synthesis reactions.
  • Another aim of the invention is to provide a chiral catalyst to be used in stereocontrolled synthesis reactions, such as to be highly reactive and provided with high regio-, chemo-, diastereo-, and enantio-selectivity.
  • Still a further aim of the present invention is to provide a chiral catalyst to be used in stereocontrolled synthesis reactions, such as to operate in mild reaction conditions, obtaining anyway high reaction rates.
  • Another aim of the invention is to allow the realization of stereocontrolled reactions, in particular reduction reactions involving the utilization of chiral catalysts and leading to the formation of optically active products with high diastereoisomeric and/or enantiomeric excesses.
  • 1,4 chiral diphosphines constituted on a 2- butene in (Z)-arrangement. More particularly, said chiral diphosphines have the following general formula 12a/12b/12g/12h: wherein:
  • R is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl C 1 -C 10 , cyclic heteroalkyl, COOR 3 , where R 3 is linear, branched, cyclic alkyl C 1 -C 10 ;
  • R' is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl Ci-C 10 , cyclic heteroalkyl, COOR 3 , where R 3 is linear, branched, cyclic alkyl C 1 -C 10 ;
  • R is hydrogen when R' is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl Ci-C 10 , cyclic heteroalkyl, COOR 3 , where R 3 is linear, branched, cyclic alkyl Ci-Ci 0 , OR 5 , where R 5 is linear, branched, cyclic alkyl Ci-Cio, or
  • R' is hydrogen when R is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl Ci-Ci 0 , cyclic heteroalkyl, COOR 3 , where R 3 is linear, branched, cyclic alkyl Ci-Ci 0 , OR 5 , where R 5 is linear, branched, cyclic alkyl Ci-Ci 0 ;
  • PY 2 is a phosphine group when Y is chosen among phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, linear, branched, cyclic alkyl C 3 -Ci 0 .
  • 1,4 chiral diphosphinites constituted on a 2-butene in (Z)-arrangement. More particularly, said chiral diphosphinites have the following general formula 12c/12d/12e/12f:
  • R is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl C 1 -C 10 , cyclic heteroalkyl, COOR 3 , where R 3 is linear, branched, cyclic alkyl C 1 -C 10 ;
  • R' is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl C 1 -C 10 , cyclic heteroalkyl, COOR 3 , where R 3 is linear, branched, cyclic alkyl C 1 -Ci 0 ;
  • R is hydrogen when R' is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl Ci-C 10 , cyclic heteroalkyl, COOR 3 , where R 3 is linear, branched, cyclic alkyl C 1 -Ci 0 , OR 5 , where R 5 is linear, branched, cyclic alkyl C 1 -C 10 , or
  • R' is hydrogen when R is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl C 1 -C 10 , cyclic heteroalkyl, COOR 3 , where R 3 is linear, branched, cyclic alkyl Ci-Ci 0 , OR 5 , where R 5 is linear, branched, cyclic alkyl Ci-Ci 0 ;
  • PY 2 is an optically active atropoisomeric phosphite derived from l,l'-bina ⁇ htol.
  • 1,4-chiral diphosphites having the following general formula, that proved to be particularly advantageous according to the present invention wherein:
  • R is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl Ci-Ci 0 , cyclic heteroalkyl, COOR 3 , where R 3 is linear, branched, cyclic alkyl C 1 -Ci 0 ;
  • R' is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl Ci-Ci 0 , cyclic heteroalkyl, COOR 3 , where R 3 is linear, branched, cyclic alkyl Ci-Ci 0 ;
  • R is hydrogen when R' is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl CpCio, cyclic heteroalkyl, COOR 3 , where R 3 is linear, branched, cyclic alkyl Ci-Ci 0 , OR 5 , where R 5 is linear, branched, cyclic alkyl Ci-Ci 0 , or
  • R' is hydrogen when R is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl C r Cio, cyclic heteroalkyl, COOR 3 , where R 3 is linear, branched, cyclic alkyl Ci-Ci 0 , OR 5 , where R 5 is linear, branched, cyclic alkyl Ci-Ci 0 ;
  • PY 2 is an optically active atropoisomeric phosphite derived from lj l'-binaphtol.
  • R is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl C 1 -Ci 0 , cyclic heteroalkyl, COOR 3 , where R 3 is linear, branched, cyclic alkyl C 1 -Ci 0 ; R' is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl Ci-Ci 0 , cyclic heteroalkyl, COOR 3 , where R 3 is linear, branched, cyclic alkyl Ci-Ci 0 ;
  • R is hydrogen when R' is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl Ci-C 10 , cyclic heteroalkyl, COOR 3 , where R 3 is linear, branched, cyclic alkyl Ci-Ci 0 , OR 5 , where R 5 is linear, branched, cyclic alkyl Ci-Cio, or
  • R' is hydrogen when R is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl Ci-Ci 0 , cyclic heteroalkyl, COOR 3 , where R 3 is linear, branched, cyclic alkyl Ci-Ci 0 , OR 5 , where R 5 is linear, branched, cyclic alkyl C 1 -Ci 0 ;
  • PY 2 is a phosphine group when Y is chosen among phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, linear, branched, cyclic alkyl C 3 -Ci 0 .
  • the chirality of said phosphorous ligands is due to the presence of two stereogenic sp 3 carbon atoms, easily modifiable according to the chiral starting diol used as precursor.
  • diphosphines, diphosphinites, diphosphites and diphosphonites according to the present invention are characterized in that the phosphorus atom are linked by a double bond in a Z arrangement, the double bond induces a strong conformational rigidity to the ligand itself.
  • the diphosphines, diphosphinites, diphosphites and diphosphonites according to this invention are advantageously utilized as chiral ligands in the preparation of complexes with transition metals.
  • Such complexes are in their turn utilized as chiral catalysts in stereocontrolled syntheses, in particular in the diastereo- and enantioselective reduction reactions, such as for instance the hydrogenation reactions, in asymmetric hydroformylations and asymmetric hydrocyanations.
  • said chiral diphosphines are prepared according to a process consisting of simple steps.
  • Said process comprises the following steps: the optically pure diol (SS)-IOa or (RR)-IOb easily available [M. Amador, X. Ariza, J. Garcia, S. Sevilla, Org. Lett., 2002, 4, 4511] is transformed into the alkyl or aryl sulphonate (RSO 2 Cl) lla/llb; then the bis-sulphonate lla/llb, dissolved in THF at -70 0 C, react with a nucleophile PY 2 " . Evaporation of the solvent and treaturation with methanol, affords the diphosphines 12a/12b optically and chemically pure.
  • SS optically pure diol
  • RR aryl sulphonate
  • Said process comprises the following steps: the optically pure diol (SS)-IOa or (RR)-IOb easily available [M. Amador, X. Ariza, J. Garcia, S. Sevilla, Org. Lett., 2002, 4, 4511] is transformed into the alkyl or aryl sulphonate (RSO 2 Cl) lla/llb; then the bis-sulphonate lla/llb, dissolved in THF at -70 0 C, react with a lithium diamino(dialkyl)phosphide (R 7 2 N) 2 PLi, 16 prepared according to literature method [L.Maier, Alkali aminophosphides, Ger. (1967) DE 1244180].
  • said chiral diphosphites are prepared according to a process consisting of simple steps.
  • a general process for the preparation of a chiral diphosphites having the general formula 14c/14d/14e/14f is schematically expounded in SCHEME 3.
  • optically pure diol (SS)-IOa or (RR)-IOb easily available [M. Amador, X. Ariza, J. Garcia, S. Sevilla, Org. Lett., 2002, 4, 4511] is reacted with the optically pure (R)-13/(S)-13 prepared according to the literature method [F. Faraone; G. Franci ⁇ ; CG. Arena; C. Graiff; M. Lanfranchi; A. Tiripicchio. Eur. J. Inorg. Chem. (1999) 1219-1227] in an inert solvent and in the presence of an HCl scavenger. The chloridrate is filtered off and evaporation of the solvent gives the optically and chemically fine diphosphites 14.
  • the chiral diphosphines, diphosphinites, diphosphites and diphosphonites according to the present invention are utilized as ligands for the complexation of transition metals, in particular the metals of the VIII group, such as for instance Ru, Rh, Pd, Pt, Ir, to form chiral complexes which act as catalysts in stereocontrolled reactions.
  • transition metals in particular the metals of the VIII group, such as for instance Ru, Rh, Pd, Pt, Ir
  • said complexes between the chiral ligand and the metal are preferably obtained by an exchange reaction between the chiral diphosphines, diphosphinites, diphosphites and diphosphonites and a complex of the chosen metal, in which the bond between metal and ligand must be more labile than the bond that will form between metal and diphosphines, diphosphinites, diphosphites and diphosphonites; in this way, the diphosphines, diphosphinites, diphosphites and diphosphonites will substitute for the ligand in the coordination to the metal, forming a preferred coordination bond.
  • the metal is utilized in coordination with ligands such as for instance 1,5-cis, cis-cyloctadiene, norbornadiene, (ethylene) 2 , triarylstibine, benzonitrile and the like.
  • ligands such as for instance 1,5-cis, cis-cyloctadiene, norbornadiene, (ethylene) 2 , triarylstibine, benzonitrile and the like.
  • the complex constituted by the chosen metal and the ligand is dissolved in a suitable solvent and then the chiral diphosphine or diphosphinite or diphosphite and or diphosphonite is added, either in the solid state or dissolved in its turn in a suitable solvent; the progress of the reaction and hence the formation is possible by the colour changes, as well as by means of spectroscopic methods, for instance by 31 P-NMR, and GC.
  • the solvent is eliminated and the chiral complex formed may be utilized as it is or it may be subjected to a further purification according to known techniques.
  • the solvents preferably utilized for the preparation of the chiral complex are, for instance, chlorinated solvents, alcohols, aromatic hydrocarbons (toluene), ethers, dimethylformamide.
  • the above chiral complexes are preferably prepared at the time when they are used as catalysts in stereocontrolled reactions.
  • the geometry of the diphosphine ligand according to this invention may determine different bonds lengths and bond angles compared to those of the known traditional ligands when coordinated to a metal, and consequently the stereoselective reactions which utilize said chiral catalysts provide advantages such as a remarkable reaction rate, mild reaction conditions, for instance as it concerns pressure and temperature conditions and the quality of catalyst utilized, as well as the possibility of using solvents having a lower ecological impact.
  • said chiral catalyst is utilized to carry out hydroformylation reactions, hydrocianation reactions.
  • the presentation of same chiral diphosphines, diphosphinites, diphosphites and diphosphonites, same chiral diphosphites and same chiral diphosphinites preparation of same chiral complexes between said diphosphines, diphosphites and diphosphinites and the metals Ru, Rh and Pd respectively, as well as the utilization of Ru and Rh complexes as chiral catalyst according to this invention are described as follows; for instance, their utilization in the reduction of methyl 3-oxo- butyrate, ⁇ -acetamidocinammic acid, ethyl-2-(benzamidomethyl)-3- oxobutanoate and in the hydroformylation of vinyl acetate and (3S,4R)-3-[(R)- l-[(ter ⁇ butyldimethylsilyl)-oxy]-eth
  • the temperature was kept below -5 0 C during sodium hydroxide addition. To complete the reaction, the solution was stirred for another 3h at 0-5 0 C and then poured in to ice water. The aqueous phase was extracted several times with ether or dichloromethane. After the collected organic extracts were dried on sodium sulphate, the solvent was removed in vacuum and the crude product recrystallized from diethyl ether. The colourless crystals can be stored at -18°C for several months without decomposition.
  • LiPPh 2 became colourless by reaction with bis-p-toluensulfonate. After the addition the temperature was allowed to warm to ambient and stirred still
  • reaction mixture is stirred overnight, and then 10 mL of diisopropylether are added to the reaction mixture. After filtration of the ammonium salt the solvent is evaporated leaving a sticky solid. This solid is washed in hexane (3x10 mL) leaving 180 mg, 78% yield, of (SS-RR)-14a.
  • reaction mixture is stirred overnight, and then 10 mL of diisopropylether are added to the reaction mixture. After filtration of the ammonium salt the solvent is evaporated leaving a sticky solid. This solid is washed in hexane (3x10 mL) leaving 360 mg, 83% yield, of (SS)-15a.
  • diphosphine (RR)-12a (0.012 eq.) and [Rh(COD) 2 ]ClO 4 (0.01 eq.) are placed in a Schlenk tube sealed with a rubber septum under an argon atmosphere; in argon-degassed acetone (5 ml) was added and the homogeneous yellow-orange solution is stirred for 15 min. The solvent was evaporated to leave diphosphine-Rh(I) complex collected as a yellow solid.
  • the substrate (1 eq.) is added to the precatalyst [Ru(p-cimene)I(RR-12a)l + I ' (0.01 eq.), followed by 20 ml of a mixture of CH 2 Cl 2 and methanol (7/3 ratio). The solution is stirred for 30 minutes and then transferred to an autoclave with a cannula.
  • the 4-vinyl ⁇ -lactam ((3S,4R)-3-[(R)-l-[(ferf- butyldimethylsilyl)-oxy]-ethyl)-4-vinil-azetidin-2-one) (0.5 mmol), the (NBD)Rh + B(Ph) 4 complex (5 mmol % to the substrate), and phosphorous ligand RR-12a (10 mmol % to the substrate) are placed in a Schlenk tube, benzene (30 mL) is added, the resulting solution is stirred for 20 minutes and then transferred to a stainless steel autoclave previously purged 5 times with a H 2 /CO mixture.
  • the autoclave is pressured and heated in an oil bath; at the end of the reaction, the autoclave is vented and the solvent is distilled.
  • Branched aldehyde ⁇ 1 H NMR: ⁇ 0.01(s, 3H), 0.03(s, 3H), 0.81(s, 6H), 1.21-1.27(d, 6H), 2.45-2.63(m, IH), 2.73-2.85(dd, IH), 3.60-3.62(d, 2H), 4.10-4.17(m, 2H), 6.2(br, IH), 9.68(s, IH); C 14 H 27 NO 3 Si calcd 285.18, found 228.2 (M + -57, -C 4 H 9 ).
  • Branched aldehyde ⁇ 1 H NMR: ⁇ 0.01(s, 3H), 0.02(s, 3H), 0.87(s, 6H),

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Abstract

Chiral diphosphines, diphosphinites, diphosphites and diphosphonites derived from (Z)-2-butenes suitable to act as chiral ligands, complexes between said diphosphines, diphosphinites, diphosphites and diphosphonites and transition metals, and their utilization as chiral catalysts in stereocontrolled reactions, such as diastereo- and enantioselective reduction reactions, diastereo- and enantioselective hydroformylation reactions, diastereo- and enantioselective hydro cyanation reactions. Process for the preparation of said chiral diphosphines, diphosphinites, diphosphites and diphosphonites and process for the preparation of said complexes and for their utilization in stereocontrolled reactions.

Description

1,4-BIS-DIPHOSPHINES. 1,4-BIS-DIPHOSPHITES AND 1,4-BIS- DIPHOSPHONITES FROM OPTICALLY ACTIVE (Z)-OLEFINES AS CHIRAL LIGANDS
Object of the present invention are chiral diphosphines, diphosphinites, diphosphites and diphosphonites, complexes between said diphosphines, diphosphinites, diphosphites and diphosphonites and transition metals, and their utilization as chiral catalysts in stereoselective reactions, such as, for instance, diastero- and enantioselective reduction reactions in general, asymmetric hydroformylations in general, asymmetric hydrocyanations in general.
Another object of the present invention is a process for the preparation of said chiral diphosphines, diphosphinites, diphosphites and diphosphonites, as well as a process for the preparation of said chiral complexes and their utilization as catalysts in diastero- and enantioselective reactions.
Further another object of the present invention is stereoselective processes, in particular diastero- and enantioselective reductions in general, which utilize said chiral catalysts. PRIOR ART
As is known, stereoselective reactions, in particular the reaction of stereocontrolled reduction, such as, for instance, diastero- and enantioselective hydrogenations, are of great importance and have been studied for a long time; in fact, such reactions lead directly to the formations of optically active compounds which would be obtainable otherwise only as racemates, with the ensuing need of subsequent separation of the enantiomers.
Besides, in these cases a further drawback may arise from the presence of an unwished enantiomer, which must be recovered or disposed of.
In general, the asymmetric stereocontrolled catalysis and in particular the stereocontrolled reduction reactions realized by means of chiral catalysts allow to obtain the optically active reaction products, often also with good enantiomeric excesses [a) H.U. Blaser, Asymmetric catalysis on industrial scale, E. SHMIDT Eds. ,2004; b) M. Beller, C. BoIm, Transition metals for organic synthesis: Building Blocks and Fine Chemicals, J. Wiley and Sons Ltd., England, vol 1 e 2, 1998; c) R. Noyori, Asymmetric Catalysis in Organic Synthesis, Wiley, New York, 1994.].
Other examples of successfully developed asymmetric catalytic reactions are those based on the formation of C-C bonds together with the concomitant formation of one or more stereogenic centre like the asymmetric hydroformylation of defines, the asymmetric allylic substitution, the hydrocyanation of olefins and aldehydes.
Many of the asymmetric catalytic reactions and namely asymmetric hydrogenations, have been studied and described that have been realized by means of special chiral catalysts, constituted by complexes between transition metals and chiral phosphines which act as ligands towards the metal.
The literature reports on different types of chiral phosphines, which can act as ligands and form chiral complexes with transition metals, such as, for instance, Ruthenium (Ru), Rhodium (Rh), Palladium (Pd), Iridium (Ir) and Platinum (Pt).
The most part of the chiral phosphines developed so far are chelating diphosphines with C2 symmetry; same selected examples are reported in figure 1.
An exception is the ferrocenyl phosphines of type 6 and ligands of type 8 (fig. 1) in which the two phosphorus atoms are different from the steric and electronic point of view.
Figure imgf000005_0001
Figure imgf000005_0002
Figure imgf000005_0003
Figure 1
The chirality can be generated from the presence of stereogenic sp3 carbon or sp3 phosphorus atoms, like in ligand 1[J. C. Poulin, T.P. Dang, H.B. Kagan, Organomet. Chem., 1975, 84, 87], 2 [J. Bakos, I. Toth, L. Marko, J. Org. Chem., 1981, 46, 5427], 3 [(a) W.S. Knowles, MJ. Sabacky, J. Chem. Soc, Chem. Commun., 1971, 481; (b) W.S. Knowles, M.J. Sabacky, B.D. Veneyard, J. WeinKauff, J. Am. Chem. Soc, 1975, 97, 2567], 4 and 9 [P.A. MacNeil, N.K. Roberts, B. Bosnich, J. Am. Chem. Soc, 1981, 103, 2273].
The chirality can be due to the presence of an atropisomeric biaryl system, i.e. a system in which the rotation around a single bond connecting two aryl groups is prevented; diphosphines of this type are for instance ligands 5 [a) A. Miyashita, H. Takaya, Tetrahedron, 1984, 40, 1245. (b) A. Miyashita, A. Yasuda, H. Takaya, K. Toriumi, T. Ito, T. Souchi, R. Noyori, J. Am. Chem. Soc, 1980, 202, 7933] and 7 [(a) T. Benincori, E. Brenna, F. Sannicolo, L. Trimarco, P. Antognazza, E. Cesarotti, F. Demartin, T. Pilati, G. Zotti, J. Organomet. Chem, 1997, 529, 445. (b) E. Cesarotti, et all. J. Org. Chem., 1996, 61, 6244. (c) T. Benincori, E. Cesarotti, O. Piccolo, F. Sannicolo, J. Org. Chem., 2000, 65, 2043].
The ligands of type 6, are based on the planar chirality of η5 coordinated 1 ,2-disubstituted cyclopentadienyl ring.
The ligands of type 8 are an example of diphosphine in which are contemporary present both the chirality due to a stereogenic sp3 centre and the atropoisomeric one [E. Cesarotti, S. Araneo, I. Rimoldi, S. Tassi, J. MoI. Catal. A: Chem., 2003, 204, 211]. The majority of these ligands present stereogenic sp3 carbon atoms and structural analogies with DIOP (1 of fig. 1). Further to the chelation with metals, these ligands generate seven-membered chelate rings; there are less examples of chelating diphosphines such as CHIRAPHOS (2 of fig. 1), which form five-membered rings upon chelation. Both these kinds of ligands, the second ones into a minor extent, are characterized by a more or less conformational flexibility.
The Rh(I)-complexes derived from these ligands, have been successfully applied in the stereoselective hydrogenation of olefinic double bonds and in the preparation of N-substituted α-aminoacids. [W.S. Knowles, Asymmetric Hydrogenation- The Monsanto L-Dopa Process, in Asymmetric Catalysis on Industrial Scale, H.U.Blaser and E.Schmidt, eds editors, 2004, Wiley, pp. 23-38; R. Selke, The Other L-Dopa Process, ibidem, pp. 39-54].
The same Rh(I)-complexes usually gives disappointing low enantioselectivities in the reduction of carbonyl groups and imines.
Rh(II)-complexes which are the catalyst of choice in the reduction of carbonyl group and Ir(I)-complexes which give catalyst able to reduce imines to amines are almost ineffective and/or give extremely low enantioselectivities when the metals are coordinated to the aforementioned ligands.
At present the catalysts for the stereocontrolled reduction, such as the diastero- and enantioselective hydrogenations of carbonyl groups, which allow to obtain the best diastereomeric and enantiomeric excesses of secondary alcohols, are those constituted by complexes between transition metals and chiral atropoisomeric diphosphine, and in particular complexes between Ru(II) and BINAP or Ru(II) and BITIOP, ligands 5 and 7 (fig. 1).
The main feature of the atropisomeric diphosphines is a seven-membered chelate ring characterized by a rather high conformational rigidity. The main problem is that of the synthesis of the chiral diphosphine which acts as ligand. In many cases, the process of synthesis of the chiral diphosphine is rather complicated, as it involves numerous steps; besides, the diphosphine which is obtained as a racemate needs a laborious resolution process, with low yields and very high costs. As a consequence, the chiral catalyst obtained by formation of a complex between the chiral diphosphine and a transition metal may be very expensive. Last but not least the introduction of structural modification in order to obtain a fine-tuning of the steric and electronic properties of the ligands is absolutely not trivial. AIM OF INVENTION An aim of the present invention is to provide chiral diphosphines, diphosphinites, diphosphites and diphosphonites suitable for acting as ligands for transition metals through the formation of particularly stable coordination bonds. An aim of the invention is to provide chiral diphosphines, diphosphates, diphosphates and diphosphonites that gather the conformational rigidity of an atropoisomeric ligands with the possibility to easily modulate the steric properties by the modification of the substituents on the stereogenic atoms.
Another aim of the invention is to provide chiral diphosphines, diphosphinites, diphosphites and diphosphonites such as to be obtainable more easily from the synthetic point of view compared to the known art.
Still another aim of the invention is to provide a process for the preparation of chiral diphosphines, diphosphinites, diphosphites and diphosphonites suitable to act as ligands for transition metals, consisting of simple steps, having contained costs and being industrially applicable.
Still a further aim of the present invention is to provide a new chiral catalyst to be used in stereocontrolled synthesis reactions. Another aim of the invention is to provide a chiral catalyst to be used in stereocontrolled synthesis reactions, such as to be highly reactive and provided with high regio-, chemo-, diastereo-, and enantio-selectivity.
Still a further aim of the present invention is to provide a chiral catalyst to be used in stereocontrolled synthesis reactions, such as to operate in mild reaction conditions, obtaining anyway high reaction rates.
Another aim of the invention is to allow the realization of stereocontrolled reactions, in particular reduction reactions involving the utilization of chiral catalysts and leading to the formation of optically active products with high diastereoisomeric and/or enantiomeric excesses. DESCRIPTION OF THE INVENTION
These aims are reached by 1,4 chiral diphosphines constituted on a 2- butene in (Z)-arrangement. More particularly, said chiral diphosphines have the following general formula 12a/12b/12g/12h:
Figure imgf000009_0001
wherein:
R is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl C1-C10, cyclic heteroalkyl, COOR3, where R3 is linear, branched, cyclic alkyl C1-C10;
R' is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl Ci-C10, cyclic heteroalkyl, COOR3, where R3 is linear, branched, cyclic alkyl C1-C10;
R is hydrogen when R' is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl Ci-C10, cyclic heteroalkyl, COOR3, where R3 is linear, branched, cyclic alkyl Ci-Ci0, OR5, where R5 is linear, branched, cyclic alkyl Ci-Cio, or
R' is hydrogen when R is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl Ci-Ci0, cyclic heteroalkyl, COOR3, where R3 is linear, branched, cyclic alkyl Ci-Ci0, OR5, where R5 is linear, branched, cyclic alkyl Ci-Ci0;
PY2 is a phosphine group when Y is chosen among phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, linear, branched, cyclic alkyl C3-Ci0.
Other aim is reached by 1,4 chiral diphosphinites constituted on a 2-butene in (Z)-arrangement. More particularly, said chiral diphosphinites have the following general formula 12c/12d/12e/12f:
Figure imgf000009_0002
wherein: R is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl C1-C10, cyclic heteroalkyl, COOR3, where R3 is linear, branched, cyclic alkyl C1-C10;
R' is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl C1-C10, cyclic heteroalkyl, COOR3, where R3 is linear, branched, cyclic alkyl C1-Ci0;
R is hydrogen when R' is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl Ci-C10, cyclic heteroalkyl, COOR3, where R3 is linear, branched, cyclic alkyl C1-Ci0, OR5, where R5 is linear, branched, cyclic alkyl C1-C10, or
R' is hydrogen when R is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl C1-C10, cyclic heteroalkyl, COOR3, where R3 is linear, branched, cyclic alkyl Ci-Ci0, OR5, where R5 is linear, branched, cyclic alkyl Ci-Ci0;
PY2 is an optically active atropoisomeric phosphite derived from l,l'-binaρhtol.
Figure imgf000010_0001
(R)-PY2 (S)-PY2
Another aim is reached by 1,4-chiral diphosphites, having the following general formula, that proved to be particularly advantageous according to the present invention
Figure imgf000011_0001
wherein:
R is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl Ci-Ci0, cyclic heteroalkyl, COOR3, where R3 is linear, branched, cyclic alkyl C1-Ci0;
R' is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl Ci-Ci0, cyclic heteroalkyl, COOR3, where R3 is linear, branched, cyclic alkyl Ci-Ci0;
R is hydrogen when R' is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl CpCio, cyclic heteroalkyl, COOR3, where R3 is linear, branched, cyclic alkyl Ci-Ci0, OR5, where R5 is linear, branched, cyclic alkyl Ci-Ci0, or
R' is hydrogen when R is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl CrCio, cyclic heteroalkyl, COOR3, where R3 is linear, branched, cyclic alkyl Ci-Ci0, OR5, where R5 is linear, branched, cyclic alkyl Ci-Ci0;
PY2 is an optically active atropoisomeric phosphite derived from lj l'-binaphtol.
Figure imgf000011_0002
(R)-PY2 (S)-PY2 Another aim is reached by 1,4- chiral diphosphonites, having the following general formula, that proved to be particularly advantageous according to the present invention
Figure imgf000012_0001
wherein:
R is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl C1-Ci0, cyclic heteroalkyl, COOR3, where R3 is linear, branched, cyclic alkyl C1-Ci0; R' is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl Ci-Ci0, cyclic heteroalkyl, COOR3, where R3 is linear, branched, cyclic alkyl Ci-Ci0;
R is hydrogen when R' is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl Ci-C10, cyclic heteroalkyl, COOR3, where R3 is linear, branched, cyclic alkyl Ci-Ci0, OR5, where R5 is linear, branched, cyclic alkyl Ci-Cio, or
R' is hydrogen when R is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl Ci-Ci0, cyclic heteroalkyl, COOR3, where R3 is linear, branched, cyclic alkyl Ci-Ci0, OR5, where R5 is linear, branched, cyclic alkyl C1-Ci0;
PY2 is a phosphine group when Y is chosen among phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, linear, branched, cyclic alkyl C3-Ci0.
In particular, the chirality of said phosphorous ligands is due to the presence of two stereogenic sp3 carbon atoms, easily modifiable according to the chiral starting diol used as precursor.
Besides, said diphosphines, diphosphinites, diphosphites and diphosphonites according to the present invention are characterized in that the phosphorus atom are linked by a double bond in a Z arrangement, the double bond induces a strong conformational rigidity to the ligand itself.
Thanks to these characteristics, the diphosphines, diphosphinites, diphosphites and diphosphonites according to this invention are advantageously utilized as chiral ligands in the preparation of complexes with transition metals. Such complexes are in their turn utilized as chiral catalysts in stereocontrolled syntheses, in particular in the diastereo- and enantioselective reduction reactions, such as for instance the hydrogenation reactions, in asymmetric hydroformylations and asymmetric hydrocyanations.
Always according to the present invention, said chiral diphosphines are prepared according to a process consisting of simple steps.
Always according to the invention and only by way of example, a general process for the preparation of a chiral diphosphines having the general formula 12a/12b/12g/12h are schematically expounded in SCHEME 1.
SCHEME 1
Figure imgf000014_0001
Said process comprises the following steps: the optically pure diol (SS)-IOa or (RR)-IOb easily available [M. Amador, X. Ariza, J. Garcia, S. Sevilla, Org. Lett., 2002, 4, 4511] is transformed into the alkyl or aryl sulphonate (RSO2Cl) lla/llb; then the bis-sulphonate lla/llb, dissolved in THF at -700C, react with a nucleophile PY2 ". Evaporation of the solvent and treaturation with methanol, affords the diphosphines 12a/12b optically and chemically pure.
Always according to the invention and only by way of example, a general process for the preparation of a chiral diphosphines having the general formula 12c/12d/12e/12f are schematically expounded in SCHEME 2. SCHEME 2
Figure imgf000015_0001
Said process comprises the following steps: the optically pure diol (SS)-IOa or (RR)-IOb easily available [M. Amador, X. Ariza, J. Garcia, S. Sevilla, Org. Lett., 2002, 4, 4511] is transformed into the alkyl or aryl sulphonate (RSO2Cl) lla/llb; then the bis-sulphonate lla/llb, dissolved in THF at -700C, react with a lithium diamino(dialkyl)phosphide (R7 2N)2PLi, 16 prepared according to literature method [L.Maier, Alkali aminophosphides, Ger. (1967) DE 1244180]. Then 17a is reacted with the optically pure (R)-13/(S)-13 prepared according to the literature method [F. Faraone; G. Franciό; CG. Arena; C. Graiff; M. Lanfranchi; A. Tiripicchio. Eur. J. Inorg. Chem. (1999) 1219-1227] in heat inert THF for 48 h according to the literature method [M. T. Reetz, A.Gosberg, R.Goddard, S. -H. Kyung. Chem. Commun., (1998), 2077-2078]. Evaporation of the solvent affords the diphosphinites 12c/12d/12e/12f optically and chemically pure.
According to the present invention, said chiral diphosphites are prepared according to a process consisting of simple steps. Always according to the invention and only by way of example, a general process for the preparation of a chiral diphosphites having the general formula 14c/14d/14e/14f is schematically expounded in SCHEME 3.
SCHEME 3
Figure imgf000016_0001
The optically pure diol (SS)-IOa or (RR)-IOb easily available [M. Amador, X. Ariza, J. Garcia, S. Sevilla, Org. Lett., 2002, 4, 4511] is reacted with the optically pure (R)-13/(S)-13 prepared according to the literature method [F. Faraone; G. Franciό; CG. Arena; C. Graiff; M. Lanfranchi; A. Tiripicchio. Eur. J. Inorg. Chem. (1999) 1219-1227] in an inert solvent and in the presence of an HCl scavenger. The chloridrate is filtered off and evaporation of the solvent gives the optically and chemically fine diphosphites 14.
In the same way the optically pure diol (SS)-IOa or (RR)-IOb is reacted with chlorodiphenylphosphine in an inert solvent, in the presence of HCl scavenger. The chloridrate is filtered off and evaporation of the solvent gives the optically and chemically fine diphosphonites ljδ^
As said already, the chiral diphosphines, diphosphinites, diphosphites and diphosphonites according to the present invention are utilized as ligands for the complexation of transition metals, in particular the metals of the VIII group, such as for instance Ru, Rh, Pd, Pt, Ir, to form chiral complexes which act as catalysts in stereocontrolled reactions.
According to the investigation, said complexes between the chiral ligand and the metal are preferably obtained by an exchange reaction between the chiral diphosphines, diphosphinites, diphosphites and diphosphonites and a complex of the chosen metal, in which the bond between metal and ligand must be more labile than the bond that will form between metal and diphosphines, diphosphinites, diphosphites and diphosphonites; in this way, the diphosphines, diphosphinites, diphosphites and diphosphonites will substitute for the ligand in the coordination to the metal, forming a preferred coordination bond. SCHEME 4
Figure imgf000018_0001
SCHEME 5
Figure imgf000018_0002
In particular, in above exchange reaction, the metal is utilized in coordination with ligands such as for instance 1,5-cis, cis-cyloctadiene, norbornadiene, (ethylene)2, triarylstibine, benzonitrile and the like.
In particular, the complex constituted by the chosen metal and the ligand is dissolved in a suitable solvent and then the chiral diphosphine or diphosphinite or diphosphite and or diphosphonite is added, either in the solid state or dissolved in its turn in a suitable solvent; the progress of the reaction and hence the formation is possible by the colour changes, as well as by means of spectroscopic methods, for instance by 31P-NMR, and GC. At the end of the reaction, the solvent is eliminated and the chiral complex formed may be utilized as it is or it may be subjected to a further purification according to known techniques.
The solvents preferably utilized for the preparation of the chiral complex are, for instance, chlorinated solvents, alcohols, aromatic hydrocarbons (toluene), ethers, dimethylformamide. The above chiral complexes are preferably prepared at the time when they are used as catalysts in stereocontrolled reactions.
Always according to the present invention, the geometry of the diphosphine ligand according to this invention may determine different bonds lengths and bond angles compared to those of the known traditional ligands when coordinated to a metal, and consequently the stereoselective reactions which utilize said chiral catalysts provide advantages such as a remarkable reaction rate, mild reaction conditions, for instance as it concerns pressure and temperature conditions and the quality of catalyst utilized, as well as the possibility of using solvents having a lower ecological impact.
Besides, said chiral catalyst have a high chemo-, enantio- and diastereoselectivity and are advantageously utilized to perform stereoselective reactions, in particular diastereo- and enantioselective reduction reactions, such as, for instance, reduction of olefins (-C=C-), reduction of ketone carbonyl groups (-C=O), reduction of imine groups (-C=N), reduction of enamines (-N-C=C-), obtaining optically active compounds with high diastereomeric and enantiomeric excesses.
Always according to the present invention, said chiral catalyst is utilized to carry out hydroformylation reactions, hydrocianation reactions. By the way of non limitative example of this invention, the presentation of same chiral diphosphines, diphosphinites, diphosphites and diphosphonites, same chiral diphosphites and same chiral diphosphinites preparation of same chiral complexes between said diphosphines, diphosphites and diphosphinites and the metals Ru, Rh and Pd respectively, as well as the utilization of Ru and Rh complexes as chiral catalyst according to this invention are described as follows; for instance, their utilization in the reduction of methyl 3-oxo- butyrate, α-acetamidocinammic acid, ethyl-2-(benzamidomethyl)-3- oxobutanoate and in the hydroformylation of vinyl acetate and (3S,4R)-3-[(R)- l-[(ter^butyldimethylsilyl)-oxy]-ethyl)-4-vinil-azetidin-2-one.
EXAMPLE 1
Preparation of the chiral diphosphine (R,R)-12a (where R = R' = Me; Y = C6H5). a) Preparation of (S,S)-bis-p-toluensulfonate (S, S)-IIa:
To a 10% solution of 3.50 g (18.30 mmol) tosyl chloride in THF or diethyl ether was added a concentrated solution of 0.85 g (7.32 mmol) diol (S,S)-10a in THF, and the reaction mixture was cooled to -15°C. Thereafter a large excess of finely powdered sodium hydroxide was added in small portions to the vigorously stirred solution. The temperature was kept below -50C during sodium hydroxide addition. To complete the reaction, the solution was stirred for another 3h at 0-50C and then poured in to ice water. The aqueous phase was extracted several times with ether or dichloromethane. After the collected organic extracts were dried on sodium sulphate, the solvent was removed in vacuum and the crude product recrystallized from diethyl ether. The colorless crystals can be stored at -180C for several months without decomposition.
(S,S)-lla was obtained with a 70% yields after crystallization from diethyl ether and characterized with a melting point m.p. = 7O0C with decomposition.
C% caicd = 56.59; H%caicd = 5.70; C%found = 56.94; H%found = 5.66 b) Preparation of LiPPh2: To a magnetically stirred solution of 0.50 ml of Ph2PCl in dried THF (10 ml) metallic lithium in excess was added. The mixture was stirred for 3 h, under argon atmosphere, during which time the solution turned deep red. A 0.26 M solution Of LiPPh2 was obtained. c) Preparation of (R,R)-12a:
A solution Of LiPPh2 (0.98 mmol; 0.26 M in THF) was dropped into a solution of (S.SMla in THF at -780C, under argon. The deep red solution of LiPPh2 became colourless by reaction with bis-p-toluensulfonate. After the addition the temperature was allowed to warm to ambient and stirred still 30 mim. The excess Of LiPPh2 was quenched by Na2SO4 10 H2O5 the mixture was filtrated, under argon. Evaporation of the solvent and treated with methanol afforded the chiral diphosphine (R,R)-12a optically and chemically pure.
[α]20 D= -50.3 (c = 0.001 M ; C3H6O); 31P-NMR (300 MHz) (C3D6O) (ppm): -1.525 (s); yield % = 95%.
EXAMPLE 2
Preparation of the chiral diphosphine (S,SV12b (where R = R' = Me; Y = C6H5). a) Preparation of (S,S)-bis-p-toluensulfonate (R-R)-Hb: To a 10% solution of 3.50 g (18.30 mmol) tosyl chloride in THF or diethyl ether was added a concentrated solution of 0.85 g (7.32 mmol) diol (R,R)-10b in THF, and the reaction mixture was cooled to -15°C. Thereafter a large excess of finely powdered sodium hydroxide was added in small portions to the vigorously stirred solution. The temperature was kept below -50C during sodium hydroxide addition. To complete the reaction, the solution was stirred for another 3h at 0-50C and then poured in to ice water. The aqueous phase was extracted several times with ether or dichloromethane. After the collected organic extracts were dried on sodium sulphate, the solvent was removed in vacuum and the crude product recrystallized from diethyl ether. The colourless crystals can be stored at -18°C for several months without decomposition.
(R,R)-llb was obtained with a 70% yields after crystallization from diethyl ether and characterized with a melting point m.p. = 700C with decomposition.
C% calcd = 56.59; H%calcd = 5.70; C%found = 56.94; H%found = 5.66 b) Preparation of LiPPh2:
To a magnetically stirred solution of 0.50 ml of Ph2PCl in dried THF (10 ml) metallic lithium in excess was added. The mixture was stirred for 3 h, under argon atmosphere, during which time the solution turned deep red. A 0.26 M solution Of LiPPh2 was obtained. c) Preparation of (S,SM2b:
A solution Of LiPPh2 (0.98 mmol; 0.26 M in THF) was dropped into a solution of (RJR)-IIb in THF at -780C, under argon. The deep red solution of
LiPPh2 became colourless by reaction with bis-p-toluensulfonate. After the addition the temperature was allowed to warm to ambient and stirred still
30 mim. The excess Of LiPPh2 was quenched by Na2SO4 - 10 H2O, the mixture was filtrated, under argon. Evaporation of the solvent and treated with methanol afforded the chiral diphosphine (S,S)-12b optically and chemically pure.
[α]2V +50 (c = 0.001 M; C3H6O); 31P-NMR (300 MHz) (C3D6O) (ppm): -1.525 (s); yield % = 95%.
EXAMPLE 3 Preparation of the chiral diphosphine (R,RM2g (where R = R' = Me; Y
= C8H9). a) Preparation of (S,S)-bis-p-toluensulfonate (S,S)-lla:
To a 10% solution of 3.50 g (18.30 mmol) tosyl chloride in THF or diethyl ether was added a concentrated solution of 0.85 g (7.32 mmol) diol (S,S)-10a in THF, and the reaction mixture was cooled to -15°C. Thereafter a large excess of finely powdered sodium hydroxide was added in small portions to the vigorously stirred solution. The temperature was kept below -50C during sodium hydroxide addition. To complete the reaction, the solution was stirred for another 3h at 0-50C and then poured in to ice water. The aqueous phase was extracted several times with ether or dichloromethane. After the collected organic extracts were dried on sodium sulphate, the solvent was removed in vacuum and the crude product recrystallized from diethyl ether. The colourless crystals can be stored at -180C for several months without decomposition.
(S,S)-lla was obtained with a 70% yields after crystallization from diethyl ether and characterized with a melting point m.p. = 700C with decomposition. C% calcd = 56.59; H%caicd = 5.70; C%found.= 56.94; H%found = 5.66 b) Preparation of bis-(3,5-dimethylphenyl)chlorophosphine:
A 0.5 M solution of [3,5-dimethylphenyl]magnesium bromide was added slowly to a solution of 3 mmol of (Et2N)PCI2 in 15 mL of THF at 00C. After 2 h, the mixture was concentrated in vacuum. Cyclohexane (20 mL) was added and the mixture was filtered through celite to provide a solution of [bis-(3,5-dimethylphenyl)](diethylamino)phosphine. Dry HCl was passed through this solution for 1 h. After filtration under a nitrogen atmosphere (in some instances, it was necessary to degas the solution to precipitate the amine hydrochloride) and concentration, the chlorophosphine was collected as straw-yellow oil. 31P-NMR (300 MHz) (CD3Cl) (ppm): 85.3 (s); yield % = 88%. c) Preparation of LiP (C8H9)2:
To a magnetically stirred solution of 2.6 mmol of (C8Hg)2PCl in dried THF (10 ml) metallic lithium in excess was added. The mixture was stirred for 3 h, under argon atmosphere, during which time the solution turned deep green. A 0.26 M solution of LiP(C8H9)2 was obtained. d) Preparation of (R,R)-12g: A solution of LiP(C8H9)2 (0.98 mmol; 0.26 M in THF) was dropped into a solution of (S,S)-lla in THF at -78°C, under argon. The deep red solution of LiP(C8H9)2 became colourless by reaction with bis-p-toluensulfonate. After the addition the temperature was allowed to warm to ambient and stirred still 30 mim. The excess of LiP(C8H9)2 was quenched by Na2SO4 - 10 H2O, the mixture was filtrated, under argon. Evaporation of the solvent and treated with methanol afforded the chiral diphosphine (R,R)-12g optically and chemically pure. 31P-NMR (300 MHz) (C3D6O) (ppm): -2.703 (s); yield % = 95%. EXAMPLE 4
Preparation of the chiral diphosphine (S,S)-12h (where R = R' = Me; Y = C8H9). a) Preparation of (S,S)-bis-p-toluensulfonate (R,R)-lla:
To a 10% solution of 3.50 g (18.30 mmol) tosyl chloride in THF or diethyl ether was added a concentrated solution of 0.85 g (7.32 mmol) diol
(R,R)-10a in THF, and the reaction mixture was cooled to -150C. Thereafter a large excess of finely powdered sodium hydroxide was added in small portions to the vigorously stirred solution. The temperature was kept below
-50C during sodium hydroxide addition. To complete the reaction, the solution was stirred for another 3 h at 0-50C and then poured in to ice water. The aqueous phase was extracted several times with ether or dichloromethane. After the collected organic extracts were dried on sodium sulphate, the solvent was removed in vacuum and the crude product recrystallized from diethyl ether. The colourless crystals can be stored at -18°C for several months without decomposition. (RJR)-IIa was obtained with a 70% yields after crystallization from diethyl ether and characterized with a melting point m.p. = 700C with decomposition.
C% Caicd = 56.59; H%calcd = 5.70; C%found = 56.94; H%found = 5.66 b) Preparation of bis-(3,5-dimethylphenyl)chlorophosphine:
A 0.5 M solution of [3,5-dimethylphenyl]magnesium bromide was added slowly to a solution of 3 mmol of (Et2N)PCI2 in 15 niL of THF at 00C.
After 2 h, the mixture was concentrated in vacuum. Cyclohexane (20 mL) was added and the mixture was filtered through celite to provide a solution of [bis-(3,5-dimethylphenyl)](diethylamino)phosphine. Dry HCl was passed through this solution for 1 h. After filtration under a nitrogen atmosphere (in some instances, it was necessary to degas the solution to precipitate the amine hydrochloride) and concentration, the chlorophosphine was collected as straw-yellow oil. 31P-NMR (300 MHz) (CD3Cl) (ppm): 85.3 (s); yield % = 88%. c) Preparation of LiP(C8Hg)2:
To a magnetically stirred solution of 2.6 mmol of (C8H9)2PC1 in dried THF (10 ml) metallic lithium in excess was added. The mixture was stirred for 3h, under argon atmosphere, during which time the solution turned deep green. A 0.26 M solution of LiP(C8H9)2 was obtained. d) Preparation of (S,S)-12h:
A solution of LiP(C8H9)2 (0.98 mmol; 0.26 M in THF) was dropped into a solution of (R,R)-lla in THF at -78°C, under argon. The deep red solution of LiP(C8H9);? became colourless by reaction with bis-p-toluensulfonate. After the addition the temperature was allowed to warm to ambient and stirred still 30 mim. The excess of LiP(C8Hg)2 was quenched by Na2SO4 - 10 H2O, the mixture was filtrated, under argon. Evaporation of the solvent and treated with methanol afforded the chiral diphosphine (S,SV12h optically and chemically pure. 31P-NMR (300 MHz) (C3D6O) (ppm): -2.703 (s); yield % = 95%.
EXAMPLE 5
Preparation of (SS-RR)-14a
36.6 mg of (SS)-IOa (PM = 116.15; 0.31 mmol) and 0.130 niL (0.95 mmol) of triethylamine are dissolved in 10 mL of toluene. The solution is cooled at 00C and a solution of the ligand (R)-13 (220 mg, 0.63 mmol) in toluene (5mL) is added dropwise within 30 minutes.
The reaction mixture is stirred overnight, and then 10 mL of diisopropylether are added to the reaction mixture. After filtration of the ammonium salt the solvent is evaporated leaving a sticky solid. This solid is washed in hexane (3x10 mL) leaving 180 mg, 78% yield, of (SS-RR)-14a.
31P-NMR (C6D6): δ = 147.1 ppm.
EXAMPLE 6
Preparation of (SS)-15a 104 mg of (SS)-IOa (PM = 116.15; 0.89 mmol), and 0.372 mL
(2.68 mmol) of triethylamine are dissolved in 10 mL of toluene. The solution is cooled at O0C and a solution of the chlorodiphenylphosphine(395 mg, 1.79 mmol) in toluene (5mL) is added dropwise within 30 minutes.
The reaction mixture is stirred overnight, and then 10 mL of diisopropylether are added to the reaction mixture. After filtration of the ammonium salt the solvent is evaporated leaving a sticky solid. This solid is washed in hexane (3x10 mL) leaving 360 mg, 83% yield, of (SS)-15a.
31P-NMR (C6D6): δ = 107.4 ppm.
EXAMPLE 7 Preparation of PdClz(R,R)-12a Complex:
A mixture of (R,R)-12a (PM = 452.2; 0.21 mmol) and (C6H5CN)2PdCl2 (PM - 383.4; 0.21 mmol) in argon-degassed acetone (5 mL) was stirred at r.t. for 30 min, under argon atmosphere; the solvent was removed by filtration to leave PdCl2(R-R)- 12a complex as a yellow solid, washed with hexane. Recrystallization of the crude product by slow diffusion of ether into a CH2Cl2-saturated solution afforded crystals suitable for X-ray structure analysis which are reported in Figure 2 and 3.
Yield % = 91% ; C% caicd = 57.21; H%calcd = 4.80; C%found = 56.26; H%found = 4.86.
31P NMR (300 MHz) (CDC13) (ppm): 24.20 (s).
EXAMPLE 8 Preparation of [Ru(p-cymene) (R,R)-12a]+r Complex.
To a Schlenk tube charged with (R,R)-12a (PM = 452.52; 9.7 mg; 2.16 x 10"2 mmol) and red brown [Ru(p-cymene)]+r (PM = 489.10; 9.6 mg; 1.96 x 10"2 mmol), was added freshly distilled argon-degassed DMF (4 ml). The mixture was stirred at 1000C for 2h. The resulting brown solution was cooled to 500C and concentrated under reduced pressure to give [Ru(/?- cymene) (R,R)-12al"T complex. The residue was left under vacuum for 2 h and then argon pressurized. The obtained ruthenium complex was utilized without other purification in the enantioselective reduction reactions.
31P-NMR (300 MHz) (CDCl3) (ppm): 31.89 (d, JP-P = 45.78 Hz), 27.14 (d, Jp.p - 49.59 Hz), (JRu.P = 576.02, JRu.P = 579.83).
EXAMPLE 9
Preparation of FRh (RR-12a)1B(Ph)£:
To a Schlenk tube charged with (R,RM2a (PM = 452.52; 9.7 mg; 2.16 x 10"2 mmol) and [Rh(NBD)]B(Ph)4 (PM = 514.28; 1.7 x 10"2 mmol), was added freshly distilled argon-degassed THF (5 ml). The mixture was stirred at r.t. for 30 min. The solvent was removed under reduced pressure to give [Rh CRR-12a)lB(ThV The obtained Rhodium complex was utilized without other purification in stereocontrolled hyroformylation reactions. EXAMPLE 10
Preparation of TRh (COD) (RR-12a)1:
The diphosphine (RR)-12a (0.012 eq.) and [Rh(COD)2]ClO4 (0.01 eq.) are placed in a Schlenk tube sealed with a rubber septum under an argon atmosphere; in argon-degassed acetone (5 ml) was added and the homogeneous yellow-orange solution is stirred for 15 min. The solvent was evaporated to leave diphosphine-Rh(I) complex collected as a yellow solid.
31P-NMR (300 MHz) (CDCl3) (ppm): 24.56 (d, JP-P = 144 Hz)
EXAMPLE 11 Preparation of PdCUSS,RR)-14a Complex:
A mixture of (SS-RR)-14a (PM = 744; 0.21 mmol) and
(C6H5CN)2PdCl2 (PM = 383.4; 0.21 mmol) in argon-degassed acetone (5 mL) was stirred at r.t. for 30 min, under argon atmosphere; the solvent was removed by filtration to leave PdCl1(SS-RR)-Ha complex as a yellow solid, which washed with hexane.
31P NMR (300 MHz) (CDC13) (ppm): 111.30 (s).
EXAMPLE 12
Preparation Qf PdCl1(SS)-ISa Complex:
A mixture of (SS)-15a (PM - 488; 0.21 mmol) and (C6H5CN)2PdCl2 (PM = 383.4; 0.21 mmol) in argon-degassed acetone (5 mL) was stirred at r.t. for 30 min, under argon atmosphere; the solvent was removed by filtration to leave PdCl?(SS)-15a complex as a yellow solid, which washed with hexane.
31P NMR (300 MHz) (CDC13) (ppm): 103.26 (s).
EXAMPLE 13 Hydrogenation of ethyl-2-(benzamidomethyl)-3-oxobutanoate
In a Schlenk tube sealed with a rubber septum under argon atmosphere the substrate (1 eq.) is added to the precatalyst [Ru(p-cimene)I(RR-12a)l+I' (0.01 eq.), followed by 20 ml of a mixture of CH2Cl2 and methanol (7/3 ratio). The solution is stirred for 30 minutes and then transferred to an autoclave with a cannula.
The stainless steel autoclave (200 mL), equipped with temperature control and magnetic stirrer, is purged 5 times with hydrogen before use. After the transfer of the reaction mixture, the autoclave is pressurized at 50atm and then warmed at 600C. At the end of the reaction the autoclave is vented, the catalyst is removed by filtration on a short pad of cellulose (DOWEX 50) and the solvent is evaporated. The conversion is determined by 1H-NMR. The diastereisomeric excess and enantiomeric excess of the product are determined by HPLC on a chiral stationary phase column (Diacel Chiralcel OD®, n-hexane/isopropanol = 9/1 0.8 mL/min, λ=210 nm). d.e.% - 43%; e.e.%=68%(RR).
EXAMPLE 14
Hydrogenation of 3-oxo-butyrate In a Schlenk tube sealed with a rubber septum under argon atmosphere the substrate (1 eq.) is added to the precatalyst [Ru(p-cimene)I(RR=12a)]+F (0.01 eq.), followed by 20 ml of distilled methanol. The solution is stirred for 30 minutes and then transferred to an autoclave with a cannula.
The stainless steel autoclave (200 mL), equipped with temperature control and magnetic stirrer, is purged 5 times with hydrogen before use. After the transfer of the reaction mixture, the autoclave is pressurized and then warmed at desired values. At the end of the reaction the autoclave is vented, the catalyst is removed by filtration on a short pad of cellulose (DOWEX 50) and the solvent is evaporated. The conversion is determined by 1H-NMR. The diastereisomeric excess and enantiomeric excess of the product are determined by GC on a chiral stationary phase column (Mega DAcTButSilBETA 25 m, internal diameter 0.35 mm) e.e.%=66%. EXAMPLE 15
Hvdroformylation of πS^R^-B-rCR^-l-rCfert-butyldimethylsilylVoxyl- ethyl)-4-vinil-azetidin-2-one
In a typical run, the 4-vinyl ^-lactam ((3S,4R)-3-[(R)-l-[(ferf- butyldimethylsilyl)-oxy]-ethyl)-4-vinil-azetidin-2-one) (0.5 mmol), the (NBD)Rh+B(Ph)4 complex (5 mmol % to the substrate), and phosphorous ligand RR-12a (10 mmol % to the substrate) are placed in a Schlenk tube, benzene (30 mL) is added, the resulting solution is stirred for 20 minutes and then transferred to a stainless steel autoclave previously purged 5 times with a H2/CO mixture. The autoclave is pressured and heated in an oil bath; at the end of the reaction, the autoclave is vented and the solvent is distilled. The branched/linear ratio, the conversion and the diastereomeric excess of the branched aldehydes are determined by 1H-NMR and GC-MS(Thermo Finnigan MD800 with GC Trace column: SE 52, length 25 mt, 0 int 0.32 mm, film 0.4-0.45 μm). d.e. (α/β) =67/33; br/lin=60/40.
Branched aldehyde α: 1H NMR: δ 0.01(s, 3H), 0.03(s, 3H), 0.81(s, 6H), 1.21-1.27(d, 6H), 2.45-2.63(m, IH), 2.73-2.85(dd, IH), 3.60-3.62(d, 2H), 4.10-4.17(m, 2H), 6.2(br, IH), 9.68(s, IH); C14H27NO3Si calcd 285.18, found 228.2 (M+ -57, -C4H9). Branched aldehyde β: 1H NMR: δ 0.01(s, 3H), 0.02(s, 3H), 0.87(s, 6H),
1.16-1.19(d, 6H), 2.53-2.69(m, IH), 2.94-3.01(dd, IH), 3.86-3.93(d, 2H), 4.13-4.20(m, 2H), 6.1(br, IH), 9.73(s, IH); C14H27NO3Si calcd 285.18, found 228.2 (M+ -57, -C4H9).
Linear aldehyde: 1H NMR: δ 0.01(s, 3H), 0.04(s, 3H), 0.85(s, 6H), 1.19-1.23(d, 6H)5 2.43-2.62(m, IH), 2.71-2.80(dd, IH), 3.59-3.63(d, 2H), 4.10-4.20(m, 2H), 6.1(br, IH), 9.77(s, IH); C14H27NO3Si calcd 285.18, found 228.2 (M+ -57, -C4H9).

Claims

1. Diphosphine compounds represented by formula 12a/12b/12g/12h:
Figure imgf000031_0001
wherein
R is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl C1-C10, cyclic heteroalkyl, COOR3, where R3 is linear, branched, cyclic alkyl Ci-Ci0; R' is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl C1-C10, cyclic heteroalkyl, COOR3, where R3 is linear, branched, cyclic alkyl C1-C10;
R is hydrogen when R' is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl Ci-C10, cyclic heteroalkyl, COOR3, where R3 is linear, branched, cyclic alkyl C1-Ci0, OR5, where R5 is linear, branched, cyclic alkyl C1-Ci0, or
R' is hydrogen when R is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl Ci-Ci0, cyclic heteroalkyl, COOR3, where R3 is linear, branched, cyclic alkyl Ci-Ci0, OR5, where R5 is linear, branched, cyclic alkyl C1-C10;
PY2 is a phosphine group when Y is chosen among phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, linear, branched, cyclic alkyl C3-C10.
2. Diphosphinite compounds represented by formula 12c/12d/12e/12f:
Figure imgf000031_0002
wherein
R is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl C1-C10, cyclic heteroalkyl, COOR3, where R3 is linear, branched, cyclic alkyl Ci-C10; R' is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl Ci-C10, cyclic heteroalkyl, COOR3, where R3 is linear, branched, cyclic alkyl C1-Ci0;
R is hydrogen when R' is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl Ci-Ci0, cyclic heteroalkyl, COOR3, where R3 is linear, branched, cyclic alkyl Ci-Ci0, OR5, where R5 is linear, branched, cyclic alkyl Ci-Cio, or
R' is hydrogen when R is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl Ci-Ci0, cyclic heteroalkyl, COOR3, where R3 is linear, branched, cyclic alkyl Ci-Ci0, OR5, where R5 is linear, branched, cyclic alkyl Ci-Ci0;
PY2 represents an optically pure phosphite group derived from 1,1 '-Bi- 2-naphthol
Figure imgf000032_0001
(R)-PY2 (S)-PY2
3. Diphosphonite compounds represented by formula 15a/15b:
Figure imgf000032_0002
wherein:
R is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl Ci-C10, cyclic heteroalkyl, COOR3, where R3 is linear, branched, cyclic alkyl C1-C10; R' is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl Ci-Ci0, cyclic heteroalkyl, COOR3, where R3 is linear, branched, cyclic alkyl Ci-C10;
R is hydrogen when R' is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl Ci-Ci0, cyclic heteroalkyl, COOR3, where R3 is linear, branched, cyclic alkyl Ci-Ci0, OR5, where R5 is linear, branched, cyclic alkyl Ci-Cio, or
R' is hydrogen when R is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl Ci-Ci0, cyclic heteroalkyl, COOR3, where R3 is linear, branched, cyclic alkyl Ci-Ci0, OR5, where R5 is linear, branched, cyclic alkyl Ci-Ci0;
PY2 is a phosphine group when Y is chosen among phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, linear, branched, cyclic alkyl C3-Ci0.
4. Diphospite compounds represented by formula 14a/14b/14c/14d:
Figure imgf000033_0001
wherein
R is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl
Ci-Cio, cyclic heteroalkyl, COOR3, where R3 is linear, branched, cyclic alkyl Ci-Ci0;
R' is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl C1-C10, cyclic heteroalkyl, COOR3, where R3 is linear, branched, cyclic alkyl C1-Ci0;
R is hydrogen when R' is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl Ci-Ci0, cyclic heteroalkyl, COOR3, where R3 is linear, branched, cyclic alkyl Ci -Ci0, OR5, where R5 is linear, branched, cyclic alkyl C1-Ci0, or
R' is hydrogen when R is chosen among phenyl, aryl, heteroaryl, linear, branched, cyclic alkyl Ci-Ci0, cyclic heteroalkyl, COOR3, where R3 is linear, branched, cyclic alkyl Ci-Ci0, OR5, where R5 is linear, branched, cyclic alkyl Ci-Ci0;
PY2 represents an optically pure phosphite group derived from 1,1 '-Bi- 2-naphthol
Figure imgf000034_0001
(R)-PY2 (S)-PY2 or PY2 may be a diphosphine group wherein Y represent a phenyl group or a phenyl group substituted with a halogen atom or a lower alkyl group or they are taken together to form a divalent hydrocarbon group, a linear alkyl or branched alkyl or with a cyclic alkyl group Ci-Ci0;
5. A process for producing chiral diphosphines as claimed in Claim 1, represented in scheme 1 and in examples 1,2,3 and 4: SCHEME 1
Figure imgf000035_0001
6. A process for producing chiral diphosphinites as claimed in Claim 2, represented in scheme 2:
SCHEME 2
Figure imgf000036_0001
7. A process for producing chiral diphosphites and chiral diphosphonites as claimed in Claim 3 and in Claim 4, represented in scheme 3 and in examples 5 and 6: SCHEME 3
Figure imgf000037_0001
8. A transition metal-phosphine or metal phosphite complexes as claimed in Claim 1, wherein metal complexes carry on a chiral ligand bonded with the metal represented in examples 7, 8, 9 and 10.
9. A transition metal-phosphinite or metal phosphinite complexes as claimed in Claim 2, wherein metal complexes carry on a chiral ligand bonded with the metal.
10. A transition metal-phosphite and transition metal-phosphonite or metal phosphite and phosphonite complexes as claimed in Claim 3 and in Claim 4, wherein metal complexes carry on a chiral ligand bonded with the metal represented in examples 11 and 12.
11. Complexes as claimed in Claims 8-10, in which the transition metals are Ru(II), Rh(I)5Pd(II) represented in example 7, 8, 9, 10, 11, 12.
12. Complexes as claimed in Claims 8-10, characterized to the fact that the metal carry on a coordinated ligand chosen between 1,5-cis, cis-cyloctadiene, norbornadiene, (ethylene)2, triarylstibine, benzonitrile and the like represented in example 7, 8, 9, 10, 11 and 12.
13. A process for producing complexes as claimed in Claims 8-12, characterized to the fact that the metal reacts with ligand such as represented in Scheme 4 and 5:
SCHEME 4
Figure imgf000038_0001
SCHEME 5
Figure imgf000038_0002
in particular, the complex constituted by the chosen metal and the ligand is dissolved in a suitable solvent and then the chiral diphosphine or diphosphinite or diphosphite and or diphosphonite is added, either in the solid state or dissolved in its turn in a suitable solvent.
14. Use of the chiral catalysts according to claims 8-12 for the realization of stereocontrolled reaction such as the reduction of olefins (-C=C-), for example the reduction of α-acetamidocinammic acid and its methyl ester.
15. Use of the chiral catalysts according to claims 8-12 for the realization of stereocontrolled reaction of prochiral substrates such as the reduction of ketone carbonyl group (-C=O), for example the reduction of methyl 3-oxo- butyrate, ethyl-2-(benzamidomethyl)-3-oxobutanoate represented in examples 13 and 14.
16. Use of the chiral catalysts according to claims 8-12 for the realization of stereocontrolled reaction of prochiral substrates such as the hydroformylation of vinyl acetate and (3S,4R)-3-[(R)-l-[(ferf- butyldimethylsilyl)-oxy]-ethyl)-4-vinil-azetidin-2-one, represented in example 15.
17. Use of the chiral catalysts according to claims 8-12 for the realization of stereocontrolled reaction of prochiral substrates such as the hydrocyanation of olefins.
PCT/EP2006/000914 2005-02-04 2006-02-02 1,4-bis-diphosphines, 1,4-bis-diphosphites and 1,4-bis- diphosphonites from optically active (z)-olefines as chiral ligands WO2006082054A1 (en)

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WO2016086837A1 (en) * 2014-12-05 2016-06-09 中国石油天然气股份有限公司 Disulfonic acid ester compound and application thereof, olefin polymerization catalyst component and olefin polymerization catalyst
EP3957643A1 (en) * 2020-08-18 2022-02-23 Evonik Operations GmbH New diphosphites based on cis-butene-1,4-diol
KR102669999B1 (en) * 2020-08-18 2024-05-29 에보니크 옥세노 게엠베하 운트 코. 카게 New diphosphites based on cis-butene-1,4-diol

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Publication number Priority date Publication date Assignee Title
WO2016086837A1 (en) * 2014-12-05 2016-06-09 中国石油天然气股份有限公司 Disulfonic acid ester compound and application thereof, olefin polymerization catalyst component and olefin polymerization catalyst
EP3957643A1 (en) * 2020-08-18 2022-02-23 Evonik Operations GmbH New diphosphites based on cis-butene-1,4-diol
US11667657B2 (en) 2020-08-18 2023-06-06 Evonik Operations Gmbh Diphosphites based on cis-butene-1,4-diol
KR102669999B1 (en) * 2020-08-18 2024-05-29 에보니크 옥세노 게엠베하 운트 코. 카게 New diphosphites based on cis-butene-1,4-diol

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