CN1314333A - Method for asymmetrically synthesizing secondary propiolic alcohol compound - Google Patents
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Abstract
By utilizing chiral alkamine or chiral amino glycol as ligand and in the presence of difluoromesylic acid metal reagent or trifluoromesylic acid metal reagent and alkali, optically active secondary propiolic alcohol compound is obtained through the addition reaction of terminal alkyne to aldehyde. The method has the advantages of moderate reaction condition, high stereo selectivity and low cost.
Description
The present invention relates to a kind of method of asymmetric synthesis secondary propiolic alcohol compound
Optically pure secondary propiolic alcohol compound is the important building block of the more synthetic biologically active compounds of Stereoselective.Asymmetric metal alkynes is an important method of synthetic this compounds to the nucleophilic addition(Adn) of aldehyde, has only the addition reaction of the asymmetric metal alkynes of minority bibliographical information to aldehyde.Document J.Am.Chem.Soc.1994 for example, 116, alkynes boron is to the asymmetric reduction reaction of aldehyde in 3151, document Chem.Lett.1980, the alkynes lithium is to asymmetric reduction reaction of aldehyde etc., document J.Am.Chem.Soc.2000 in 255,122,1806 are reported in trifluoromethanesulfonic acid zinc, alkali and N, and N-dimethyl norephedrine exists down, and asymmetric terminal alkynes obtains the secondary propiolic alcohol compound of highly-solid selectively to the addition reaction of aldehyde.
The method that the purpose of this invention is to provide a kind of asymmetric synthesis secondary propiolic alcohol compound.
The invention provides a kind of method of asymmetric synthesis secondary propiolic alcohol compound, promptly with chiral amino alcohol or chiral amino glycol as part, after the coordination, add terminal alkynes and aldehyde reaction and generate secondary propiolic alcohol compound in aprotic solvent, reaction formula is as follows:
A is Difluore methane-sulfonic acid metal reagent or trifluoromethanesulfonic acid metal reagent, and the useful molecules general formula is described as M (OSO
2CF
2H)
nOr M (OSO
2CF
3)
n, wherein M=zinc, silver, cadmium, mercury, indium, lead, antimony, bismuth, ytterbium or tin, n=1-3, b are chiral amino alcohol or chiral amino glycol part and when above-mentioned reactant had the trifluoromethanesulfonic acid zincon, part used in the present invention only was the chiral amino glycol.Above-mentioned R
1Or R
2=C
1-20Alkyl, aryl, substituted aryl or heteroaryl etc., described heteroatoms is N, O or S; Described alkali is triethylamine, diisopropyl ethyl amine, N, the amine that contains lone-pair electron on the nitrogen-atoms such as dinethylformamide, pyridine, 1,8-diazabicyclo [5.4.0] undecane-7-alkene (DBU), 1,5-diazabicyclo [4.3.0] nonane-5-alkene (DBN) etc.; Described chiral amino alcohol ligand is N, N-dimethyl norephedrine or N-methylephedrine etc.; Described chiral amino glycol part is that general molecular formula is
Chirality 2-disubstituted amido-1-(4-substituted-phenyl)-1, ammediol, R=H, NO in the formula
2, SO
2Me, COCH
3, R
3Or R
4=C
1-6Alkyl or cycloalkyl, R
1And R
2, R
3And R
4It is identical or different group; Described aprotic solvent is toluene, methylene halide, haloform, tetracol phenixin, tetrahydrofuran (THF), acetonitrile, acetone, ethanol, methyl-sulphoxide etc.
Specifically, the inventive method is in the time of-10 ℃～100 ℃, in aprotic solvent, adds metal reagent, chiral amino alcohol or chiral amino glycol part, alkali, terminal alkynes and aldehyde, fully obtains secondary propiolic alcohol compound after the reaction.Aldehyde wherein: alkynes: part: metal reagent: the mol ratio of alkali is 1: 0.5-5: 0.5-5: 0.2-5: 0.1-5 is recommended as 1: 0.8-2: 0.8-2: 0.5-2: 0.5-2.Reaction times is 0.5-60 hour, also can prolong the reaction times in the reaction or increase the reactant consumption.
The present invention compares with the technology of bibliographical information, reaction conditions gentleness, stereoselectivity height, the chiral ligand low price, and Difluore methane-sulfonic acid zinc cheaply is easy to get, and chiral ligand 2-(N, the N-disubstituted amido)-and 1-(4-substituted-phenyl)-1, ammediol is also more practical than N-methylephedrine.
Following examples help to understand the present invention, but are not limited to content of the present invention
Embodiment 1
(S)-preparation of 1-cyclohexyl-3-phenyl-2-propine-1-alcohol
Under nitrogen protection, Difluore methane-sulfonic acid zinc (180mg, 0.55mmol; 1.1eq) and (-)-N, N-dimethyl norephedrine (108mg, 0.602mmol; 1.2eq) toluene (2mL) solution in, add triethylamine (61mg, 0.602mmol; 1.2eq), mixing solutions at room temperature stirs 2h, adds phenylacetylene (61mg; 0.6mmol, 1.2eq), add hexamethylene aldehyde (58mg) behind the stirring 0.5h under the room temperature; stir 12h, add saturated aqueous ammonium chloride (3mL), extracted with diethyl ether (3 * 10mL).The organic solvent that merges washs anhydrous sodium sulfate drying with saturated nacl aqueous solution.Product obtains 96mg (S)-1-cyclohexyl-3-phenyl-2-propine-1-alcohol with the silica gel column chromatography separation, and yield is 90%.The 97%ee value is measured with chirality HPLC post.
1H?NMR(300?MHz,CDCl
3)δ7.38-7.45(m,2H),7.30-7.24(m,3H),4.40-4.30(d,J=6.0?Hz,1H),2.00-1.58(m,1H),1.36-1.05(m,11H)。
Embodiment 2
(5)-preparation of 4-methyl isophthalic acid-phenyl-1-pentyne-3-alcohol
Under nitrogen protection, Difluore methane-sulfonic acid zinc (180mg, 0.55mmol; 1.1eq) and (-)-N, N-dimethyl norephedrine (108mg, 0.602mmol; 1.2eq) toluene (2mL) solution in, add triethylamine (61mg, 0.602mmol; 1.2eq), mixing solutions at room temperature stirs 2h, adds phenylacetylene (61mg; 0.6mmol, 1.2eq), add isobutyric aldehyde (43mg) behind the stirring 0.5h under the room temperature; stir 24h, add saturated aqueous ammonium chloride (3mL), extracted with diethyl ether (3 * 10mL).The organic solvent that merges washs anhydrous sodium sulfate drying with saturated nacl aqueous solution.Product obtains 44mg (S)-4-methyl isophthalic acid-phenyl-1-pentyne-3-alcohol with the silica gel column chromatography separation, and yield is 92%.The 97%ee value is measured with chirality HPLC post.
1H?NMR(300?MHz,CDCl
3)δ7.4(m,2H),7.25(m.3H),4.38(d,J=6.0?Hz,1H),2.04(d,J=5.7?Hz,1H),1.97(m,1H),1.05(dd,J=6.7?Hz,6H)。
Embodiment 3
In the following table in the sequence number 7 mol ratio of aldehyde, alkynes, part, metal reagent and alkali be 1: 2.0: 2.0: 0.8: 3.0, the mol ratio of aldehyde, alkynes, part, metal reagent and alkali is 1: 0.6: 2 in the sequence number 11,12: 2: 5, the mol ratio of aldehyde, alkynes, part, metal reagent and alkali was 1: 2.0: 0.5 in the sequence number 15: 5: 0.5.
aAbsolute configuration is definite according to comparing with known compound.
bThe ee value is measured with chirality HPLC post.Experimental procedure and other experiment condition are with embodiment 1:
Embodiment 4
(R)-preparation of 1-cyclohexyl-3-phenyl-2-propine-1-alcohol
Under nitrogen protection; trifluoromethanesulfonic acid zinc (200mg, 0.55mmol is 1.1eq) with (1S; 2S)-(+)-N; the N-dimethylamino)-and 1-(4-nitrophenyl)-1, ammediol (127mg, 0.602mmol; 1.2eq) THF (2mL) solution in; the adding triethylamine (61mg, 0.602mmol, 1.2eq); mixing solutions at room temperature stirs 2h; the adding phenylacetylene (61mg, 0.6mmol, 1.2eq); add hexamethylene aldehyde (58mg) after stirring 0.5h under the room temperature; stir 12h, add saturated aqueous ammonium chloride (3mL), extracted with diethyl ether (3 * 10mL).The organic solvent that merges washs anhydrous sodium sulfate drying with saturated nacl aqueous solution.Product obtains 96mg (R)-1-cyclohexyl-3-phenyl-2-propine-1-alcohol with the silica gel column chromatography separation, and yield is 73%.The 97%ee value is measured with chirality HPLC post.
1H?NMR(300?MHz,CDCl
3)δ7.38-7.45(m,2H),7.30-7.24(m.3H),4.40-4.30(d,J=6.0?Hz,1H),2.00-1.58(m,1H),1.36-1.05(m,11H)。
Embodiment 5
(K)-preparation of the preparation of 4-methyl isophthalic acid-phenyl-1-pentyne-3-alcohol
Under nitrogen protection; trifluoromethanesulfonic acid zinc (360mg; 1mmol, 2eq) and (1S, 2S)-(+)-N; N-dicyclohexyl amino)-1-(4-formylphenyl)-1; (0.602mmol in methylene dichloride 1.2eq) (2mL) solution, adds DBU (0.602mmol to ammediol; 1.2eq); mixing solutions at room temperature stirs 2h, adds phenylacetylene (122mg, 1.2mmol; 2.4eq); stir under the room temperature add behind the 0.5h isobutyric aldehyde (86mg, 2.4eq), 80 ℃ of reactions 5 hours; add saturated aqueous ammonium chloride (3mL), extracted with diethyl ether (3 * 10mL).The organic solvent that merges washs anhydrous sodium sulfate drying with saturated nacl aqueous solution.Product obtains 88mg (R)-4-methyl isophthalic acid-phenyl-1-pentyne-3-alcohol with the silica gel column chromatography separation, and yield is 61%.The 87%ee value is measured with chirality HPLC post.
1H?NMR(300?MHz,CDCl
3)δ7.4(m,2H),7.25(m.3H),4.38(t,J=6.0?Hz,1H),2.04(d,J=5.7?Hz,1H),1.97(m,1H),1.05(dd,J=6.7Hz,6H)。
Embodiment 6
In the following table
aAbsolute configuration is definite according to comparing with known compound.
bThe ee value is measured with chirality HPLC post.
cToluene is as solvent.
dTHF is as solvent.Trifluoromethanesulfonic acid zinc in the sequence number 1,2 and 5: part: alkynes: aldehyde: alkali=2: 1: 1.2: 1.1: 1.2, other trifluoromethanesulfonic acid zinc: part: alkynes: aldehyde: alkali=1.2: 1: 1.2: 1.1: 1.2. experimental procedure and other condition were with embodiment 4:
Embodiment 7
(S)-preparation of 1-cyclohexyl-3-phenyl-2-hexin-1-alcohol
Under nitrogen protection, and Difluore methane-sulfonic acid zinc (180mg, 0.55mmol, 1.1eq) and (1S, 2S)-(+)-N, N-dimethylamino)-1-(4-nitrophenyl)-1, ammediol (127mg, 0.602mmol, CH 1.2eq)
3In CN (2mL) solution, add 1, and 5-diazabicyclo [4.3.0] nonane-5-alkene (0.1mmol, 0.2eq), mixing solutions at room temperature stirs 2h, adding benzene pentyne (61mg, 0.6mmol, 1.2eq), add isobutyric aldehyde (58mg) after stirring 0.5h under the room temperature, stir 12h, add saturated aqueous ammonium chloride (3mL), extracted with diethyl ether (3 * 10mL).The organic solvent that merges washs anhydrous sodium sulfate drying with saturated nacl aqueous solution.Product obtains 96mg (R)-1-cyclohexyl-6-phenyl-2-hexin-1-alcohol with the silica gel column chromatography separation, and yield is 89%.The 93%ee value is measured with chirality HPLC post.
1H?NMR(300?MHz,CDCl
3)δ7.10-7.25(m,5H),4.40-4.30(d,J=6.8?Hz,1H),2.29(m,2H),2.15(2H,m),2.00-1.58(m,1H),1.36-1.05(m,8H)。
Embodiment 8
(R)-preparation of 1-cyclopropyl-3-phenyl-2-propine-1-alcohol
Under nitrogen protection; Difluore methane-sulfonic acid zinc (327mg, 1mmol is 2eq) with (1S; 2S)-(+)-N; the N-dimethylamino)-and 1-(4-nitrophenyl)-1, ammediol (127mg, 0.602mmol; 1.2eq) toluene (2mL) solution in; the adding triethylamine (132mg, 1.2mmol, 2.4eq); mixing solutions at room temperature stirs 2h; the adding phenylacetylene (132mg, 1.2mmol, 2.4eq); add ring propionic aldehyde (83mg) after stirring 0.5h under the room temperature; 60 ° of G stir 1h, add saturated aqueous ammonium chloride (3mL), extracted with diethyl ether (3 * 10mL).The organic solvent that merges washs anhydrous sodium sulfate drying with saturated nacl aqueous solution.Product obtains 88mg (R)-1-cyclopropyl-3-phenyl-2-propine-1-alcohol with the silica gel column chromatography separation, and yield is 92%.The 77%ee value is measured with chirality HPLC post.
1H?NMR(300MHz,CDCl
3)δ7.4(m,2H),7.25(m.3H),4.38(d,J=6.0?Hz,1H),2.04(d,J=5.7?Hz,1H),1.97(m,1H),1.05(d,J=6.7?Hz,4H)。
Experimental procedure and other experiment condition are with embodiment 4 in embodiment 9 following tables:
| Sequence number | Aldehyde | Alkynes | Reaction times (h) | Yield % | Absolute configuration a | ????Ee％ c |
| ????1 ????2 | Hexamethylene aldehyde ring propionic aldehyde | Benzene butine benzene octyne | ????12 ????18 | ????86 ????76 | ????R ????R | ????98 ????93 |
aAbsolute configuration is definite according to comparing with known compound.
bThe ee value is measured with chirality HPLC post.
cTHF is as solvent.
Embodiment 10
(R)-preparation of 1-cyclohexyl-3-p-methoxyphenyl-valerylene-1-alcohol
Under nitrogen protection, and Difluore methane-sulfonic acid zinc (540mg, 1.6mmol, 3.3eq) and (1S, 2S)-(+)-N-methyl-N-butyl amino)-1-phenyl-1, ammediol (97.5mg, 0.502mmol, CHCl 1.0eq)
3(2mL) in the solution, add 1,8-diazabicyclo [5.4.0] undecane-7-alkene (0.602mmol, 1.2eq), mixing solutions at room temperature stirs 6h, adds anisole acetylene (79mg, 0.6mmol, 1.2eq or 316mg, 2.4mmol, 4.8eq), add hexamethylene aldehyde (67mg) after stirring 0.5h under the room temperature, stir 12h, add saturated aqueous ammonium chloride (3mL), extracted with diethyl ether (3 * 10mL).The organic solvent that merges washs anhydrous sodium sulfate drying with saturated nacl aqueous solution.Product obtains 124mg (R)-1-cyclohexyl-3-p-methoxyphenyl-valerylene-1-alcohol with the silica gel column chromatography separation, and yield is 83%.The 76%ee value is measured with chirality HPLC post.
1H?NMR(300?MHz,CDCl
3)δ7.2(m,2H),6.9(m.2H),4.5(d,J=6.2Hz,1H),3.8(s,3H),2.5(m,1H),1.45-1.55(m,9H)。
Embodiment 11
(R)-preparation of the 1-tertiary butyl-5-phenyl-valerylene-1-alcohol
Under nitrogen protection; trifluoromethanesulfonic acid zinc (200mg, 0.55mmol is 1.1eq) with (1S; 2S)-(+)-N; the N-dimethylamino)-and 1-(4-methylsulfonyl phenyl)-1, ammediol (164mg, 0.602mmol; 1.2eq) methyl-sulphoxide (2mL) solution in; the adding diisopropyl ethyl amine (77mg, 0.602mmol, 1.2eq); mixing solutions at room temperature stirs 2h; adding benzene butine (78mg, 0.6mmol, 1.2eq); add tertiary butyl formaldehyde (47mg) after stirring 0.5h under the room temperature; 50 ° of G stir 12h, add saturated aqueous ammonium chloride (3mL), extracted with diethyl ether (3 * 10mL).The organic solvent that merges washs anhydrous sodium sulfate drying with saturated nacl aqueous solution.Product obtains 108mg (the R)-1-tertiary butyl-5-phenyl-valerylene-1-alcohol with the silica gel column chromatography separation, and yield is 91%.The 88%ee value is measured with chirality HPLC post.
1H?NMR(300?MHz,CDCl
3)δ716(m,5H),4.25(d,J=6.4?Hz,1H),2.44(m,4H),1.01(s,6H)。
Embodiment 12
(S)-preparation of 1-cyclopropyl-3-phenyl-2-propine-1-alcohol
Under nitrogen protection, and the Difluore methane-sulfonic acid cadmium (224mg, 0.55mmol, 1.1eq) and (1S, 2S)-(+)-N, N-dimethylamino)-1-(4-nitrophenyl)-1, ammediol (127mg, 0.602mmol, CH 1.2eq)
3In CN (2mL) solution, add triethylamine (61mg, 0.602mmol, 1.2eq), mixing solutions at room temperature stirs 2h, adds phenylacetylene (61mg, 0.6mmol, 1.2eq or 46mg, 0.45mmol, 0.9eq), add ring propionic aldehyde (58mg) after stirring 0.5h under the room temperature, 85 ° of G stir 8h down, add saturated aqueous ammonium chloride (3mL), extracted with diethyl ether (3 * 10mL).The organic solvent that merges washs anhydrous sodium sulfate drying with saturated nacl aqueous solution.Product obtains 96mg (S)-1-cyclopropyl-3-phenyl-2-propine-1-alcohol with the silica gel column chromatography separation, and yield is 80%.The 76%ee value is measured with chirality HPLC post.
1H?NMR(300?MHz,CDCl
3)δ7.4(m,2H),7.25(m.3H),4.38(d,J=6.0Hz,1H),2.04(d,J=5.7Hz,1H),1.97(m,1H),1.05(d,J=6.7?Hz,4H)。
Embodiment 13
(S)-preparation of 2-methyl-7-(N-methyl-2-pyrroles)-4-heptyne-3-alcohol
Under nitrogen protection; silver trifluoromethanesulfonate (141mg; 0.55mmol; 1.1eq) and N-methylephedrine (0.602mmol; 1.2eq) methylene dichloride (2mL) solution in; the adding lutidine (61mg, 0.602mmol, 1.2eq); mixing solutions at room temperature stirs 2h; adding N-methyl-2-pyrroles's butine (80mg, 0.6mmol, 1.2eq); add isobutyric aldehyde (43mg) after stirring 0.5h under the room temperature; 85 ° of G stir 5h down, add saturated aqueous ammonium chloride (3mL), extracted with diethyl ether (3 * 10mL).The organic solvent that merges washs anhydrous sodium sulfate drying with saturated nacl aqueous solution.Product obtains 102mg (S)-2-methyl-7-(N-methyl-2-pyrroles)-4-heptyne-3-alcohol with the silica gel column chromatography separation, and yield is 90.5%.The 57%ee value is measured with chirality HPLC post.
1H?NMR(300?MHz,CDCl
3)δ6.8(m,1H),6.4(m,1H),5.9(m,2H),3.5(s,3H),3.35(s,2H),2.0(s,1H)。
Embodiment 14
(S)-preparation of 2-methyl-7-phenyl-4-heptyne-3-alcohol
Under nitrogen protection; Difluore methane-sulfonic acid bismuth (94mg; 0.2mmol, 0.2eq) and (1S, 2S)-(+)-N; the N-dimethylamino)-1-(4-nitrophenyl)-1; ammediol (127mg, 0.602mmol is in acetone 1.2eq) (2mL) solution; add pyrimidine (1.8mmol; 3.6eq), mixing solutions at room temperature stirs 2h, adds benzene butine (61mg; 0.6mmol; 1.2eq), adding isobutyric aldehyde (43mg) behind the stirring 0.5h under the room temperature, 85 ° of G stir 5h down; add saturated aqueous ammonium chloride (3mL), extracted with diethyl ether (3 * 10mL).The organic solvent that merges washs anhydrous sodium sulfate drying with saturated nacl aqueous solution.Product obtains 103mg (S)-2-methyl-7-phenyl-4-heptyne-3-alcohol with the silica gel column chromatography separation, and yield is 93%.The 71%ee value is measured with chirality HPLC post.
1H?NMR(300?MHz,CDCl
3)δ7.4(m,2H),7.25(m.3H),4.38(d,J=6.0?Hz,1H),2.1-2.15(m,4H)2.04(d,J=5.7?Hz,1H),1.97(m,1H),1.05(dd,J=6.7Hz,6H)。
Embodiment 15
(R)-preparation of 1-phenyl-3-dodecyne-2-alcohol
Under nitrogen protection; trifluoromethanesulfonic acid indium (286mg; 0.55mmol, 1.1eq) and (1S, 2S)-(+)-N; the N-dimethylamino)-1-(4-nitrophenyl)-1; ammediol (127mg, 0.602mmol is in chloroform 1.2eq) (2mL) solution; add methylethyl amine (0.602mmol; 1.2eq), mixing solutions at room temperature stirs 2h, adds hendecyne (91mg; 0.6mmol; 1.2eq), adding phenyl aldehyde (64mg) behind the stirring 0.5h under the room temperature, 0 ° of G stirs 24h down; add saturated aqueous ammonium chloride (3mL), extracted with diethyl ether (3 * 10mL).The organic solvent that merges washs anhydrous sodium sulfate drying with saturated nacl aqueous solution.Product obtains 131mg (R)-1-phenyl-2-dodecyne-1-alcohol with the silica gel column chromatography separation, and yield is 93%.The 71%ee value is measured with chirality HPLC post.
1H?NMR(300?MHz,CDCl
3)δ7.35(m,2H),7.20(m.3H),5.3(s,1H),2.3(m,2H),1.55(m,4H),1.35(m,4H),0.9-1.0(m,13H)。
Claims (7)
1. the method for a synthesizing secondary propiolic alcohol compound, when it is characterized in that-10 ℃～100 ℃, with chiral amino alcohol or chiral amino glycol as part, in aprotic solvent after the coordination, add terminal alkynes and aldehyde reaction 0.5-60h, aldehyde: alkynes: part: Difluore methane-sulfonic acid metal reagent or trifluoromethanesulfonic acid metal reagent: the mol ratio of alkali is 1: 0.5-5: 0.5-5: 0.2-5: 0.1-5, generate optically pure secondary propiolic alcohol compound, and when reactant has the trifluoromethanesulfonic acid zincon, part only is the chiral amino glycol, and described aldehyde is C
1-20Aromatic aldehyde, substituted aroma aldehyde, assorted aromatic aldehyde and alkanoic.
2. the method for synthesizing secondary propiolic alcohol compound as claimed in claim 1, it is characterized in that alkali is amine, the pyridine, 1 that contains lone-pair electron on the nitrogen-atoms, 8-diazabicyclo [5.4.0] undecane-7-alkene, 1,5-diazabicyclo [4.3.0] nonane-5-alkene, diisopropyl ethyl amine.
3. the method for synthesizing secondary propiolic alcohol compound as claimed in claim 1, the metal that it is characterized in that described Difluore methane-sulfonic acid metal reagent or trifluoromethanesulfonic acid metal reagent is zinc, silver, cadmium, mercury, indium, lead, antimony, bismuth, ytterbium or tin.
4. the method for synthesizing secondary propiolic alcohol compound as claimed in claim 1 is characterized in that described chiral amino alcohol ligand is chirality N, N-dimethyl norephedrine or N-methylephedrine, and described chiral amino glycol part is that molecular formula is
Chirality 2-disubstituted amido-1-(4-substituted-phenyl)-1, ammediol, R=H, NO in the formula
2, SO
2Me, COCH
3, R
3Or R
4=C
1-6Alkyl or cycloalkyl, R
3And R
4It is identical or different group.
5. the method for synthesizing secondary propiolic alcohol compound as claimed in claim 1 is characterized in that aprotic solvent is toluene, methylene halide, haloform, tetracol phenixin, tetrahydrofuran (THF), acetonitrile, acetone, methyl-sulphoxide.
6. the method for synthesizing secondary propiolic alcohol compound as claimed in claim 1 is characterized in that described terminal alkynes is C
1-20The terminal alkynes of aromatic end alkynes, substituted aroma, heteroaryl and fatty terminal alkynes.
7. the method for synthesizing secondary propiolic alcohol compound as claimed in claim 1, it is characterized in that aldehyde: alkynes: chiral amino alcohol ligand: metal reagent: the mol ratio of alkali is 1: 0.8-2: 0.8-2: 0.5-2: 0.5-2.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6586644B2 (en) * | 2001-10-05 | 2003-07-01 | Erick M. Carreira | Process for producing optically active propargyl alcohols |
| WO2004087628A1 (en) * | 2003-04-04 | 2004-10-14 | Shanghai Institute Of Organic Chemistry, Chinese Academy Of Sciences | An amino alcohol ligand and its use in preparation of chiral proparglic tertiary alkohols and tertiary amines via enantioselective additon reaction |
| CN1331601C (en) * | 2003-05-16 | 2007-08-15 | 中国科学院上海有机化学研究所 | Method of Chiral alkamine ligand used as catalyst of asymmetric addition process for terminal alkyne to fluoroalkylaryl ketone |
| CN106188106A (en) * | 2016-07-06 | 2016-12-07 | 罗梅 | Zinc complex crystal |
| CN113474315A (en) * | 2019-02-21 | 2021-10-01 | 深圳艾欣达伟医药科技有限公司 | Method for producing secondary alcohol with high mirror image selectivity |
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2001
- 2001-03-23 CN CN 01105779 patent/CN1197836C/en not_active Expired - Fee Related
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6586644B2 (en) * | 2001-10-05 | 2003-07-01 | Erick M. Carreira | Process for producing optically active propargyl alcohols |
| WO2004087628A1 (en) * | 2003-04-04 | 2004-10-14 | Shanghai Institute Of Organic Chemistry, Chinese Academy Of Sciences | An amino alcohol ligand and its use in preparation of chiral proparglic tertiary alkohols and tertiary amines via enantioselective additon reaction |
| US7439400B2 (en) | 2003-04-04 | 2008-10-21 | Shanghai Institute Of Organic Chemistry, Chinese Academy Of Sciences | Amino alcohol ligand and its use in preparation of chiral proparglic tertiary alcohols and tertiary amines via enantioselective addition reaction |
| CN1331601C (en) * | 2003-05-16 | 2007-08-15 | 中国科学院上海有机化学研究所 | Method of Chiral alkamine ligand used as catalyst of asymmetric addition process for terminal alkyne to fluoroalkylaryl ketone |
| CN106188106A (en) * | 2016-07-06 | 2016-12-07 | 罗梅 | Zinc complex crystal |
| CN113474315A (en) * | 2019-02-21 | 2021-10-01 | 深圳艾欣达伟医药科技有限公司 | Method for producing secondary alcohol with high mirror image selectivity |
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