CN100415703C - Process for preparing optically active beta-hydroxyketone - Google Patents
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- CN100415703C CN100415703C CNB2006100187386A CN200610018738A CN100415703C CN 100415703 C CN100415703 C CN 100415703C CN B2006100187386 A CNB2006100187386 A CN B2006100187386A CN 200610018738 A CN200610018738 A CN 200610018738A CN 100415703 C CN100415703 C CN 100415703C
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Abstract
The present invention relates to a method for preparing optically active beta-hydroxyketone, which comprises the following steps: in the presence of (S)-proline, acetone and chiral glycol or chiral diphenol are mixed in an organic solvent at the temperature of-20 DEG C to 110 DEG C and then are added with aldehyde to be stirred for reaction for 8 to 96 hours. After the purification processing of reaction products, chiral beta-hydroxyketone is obtained. In the presence of chiral additives, the present invention obtains chiral beta-hydroxyketone in a highly corresponding selective mode by the catalysis of the direct asymmetric aldol reaction by simple organic small molecules. The present invention has obvious characteristics of cheaply and easily obtained chiral catalysts, mild reaction condition, simple process, simply and easily obtained raw materials, high utilization rate of atoms, low cost, high purity of enantiomers, etc.
Description
Technical field
The present invention describes by catalytic direct asymmetric aldol addition, the photoactive beta-hydroxy ketone of high enantioselectivity ground preparation, belongs to chipal compounds and prepares chemical field.
Background technology
Optically active beta-hydroxy ketone is the important chipal compounds with two typical functional groups, and they are widely used in the preparation of chiral drug, natural product etc.
The Aldol addition reaction is the important method of preparation optically active beta-hydroxy ketone, and this method is divided into Mukaiyama type aldol reaction and direct aldol reacts two classes.Mukaiyama type aldol reaction is that in advance that reactive behavior is poor ketone and metal reagent, silica reagent or borane reagent reaction is converted into the stronger enolate of reactive behavior, obtains chiral beta-hydroxy ketone with aldehyde addition posthydrolysis then in chiral environment.This method requires relatively harsher to reaction conditions, require the anhydrous and oxygen-free operational condition, and used enolization reagent is relatively more expensive and stoichiometric often.The aldol repercussion study of this class is morning, and existing more summary [(a) S.G.Nelson, Tetrahedron:Asymmetry 1998,9,357-389. (b) R.Mahrwald, Chem.Rev.1999,99,1095-1120. (c) S.E.Denmark, Acc.Chem.Res 2000,33,432-440. (d) C.Palomo, M.Oiarbide, J.M.Garcia, Chem.Soc.Rev. 2004,33,65-67].In recent years, directly the research of aldol reaction has obtained bigger progress, and the chiral catalyst of a few types is applied in this class reaction and has obtained result preferably.Compared with the reaction of Mukaiyama type, directly the aldol reaction does not need in advance ketone to be converted into active stronger enolate, and only need get final product highly selective under the chipal compounds effect of catalytic amount obtains the photolytic activity product.This direct aldol addition reaction, the atom utilization height, the small molecules chipal compounds that usually uses single component, easily preparation is as chiral catalyst, and the reaction conditions gentleness has very high prospects for commercial application.About direct aldol addition reaction, in recent years existing more summary [(a) B.Alcaide, P.Almendors, Eur.J.Org Chem. 2002,1595-1601. (b) E.R.Jarvo, S.J.Miller, Tetrohedron 2002,58,2481-2495. (c) P.I.Dalko, L.Moisan, Angew.Chem.Int.Ed.2001,40,3726-3748. (d) P.I.Dalko, L.Moisan, Angew.Chem.Int.Ed.2004,43,5138-5175. (e) B.List, Tetrahedron 2002,58,5573-5590.]
The metal complex of some organic molecules is directly showing reasonable effect in the aldol reaction.[(a) Kumagai, N.; Matsunaga, S.; Kinoshita, T.; Harada, S.; Okada, S.; Sakamoto, S.; Yamaguchi, K.; Shibasaki, M.J.Am.Chem.Soc.2003,125,2169-2178. (b) Yoshikawa, N.; Yamada, Y.M.A.; Das, J.; Sasai, H.; Shibasaki, M.J. Am.Chem.Soc.1999,121,4168-4178. (c) Yamada, Y.M.A.; Yoshikawa, N.; Sasai, H.; Shibasaki, M.Angew.Chem.Int.Ed.1997,36,1871-1873. (d) Yoshikawa, N.; Kumagai, N.; Matsunaga, S.; Moll, G.; Ohshima, T.; Suzuki, T.; Shibasaki, M.J.Am.Chem.Soc.2001,123,2466-2468. (e) Yamada, Y.M.A.; Shibasaki, M.Tetrahedron Lett.1998,39,5561-5564. (f) Kumagai, N.; Matsunaga, S.; Yoshikawa, N.; Ohshima, T.; Shibasaki, M.Org.Lett.2001,3,1539-1542. (g) Trost, B.M.; Ito, H.J.Am.Chem.Soc.2000,122,12003-12004. (h) Trost, B.M.; Ito, H.; Silcoff, E.R.J.Am.Chem.Soc.2001,123,3367-3368. (i) Trost, B.M.; Silcoff, E.R.; Ito, H.Org.Lett.2001,3,2497-2500. (j) Trost, B.M.; Fettes, A.; Shireman, B.T.J.Am.Chem.Soc.2004,126,2660-2661.] but the metal complex of these organic molecules be difficult to synthetic and be relatively more responsive water, this has just limited its range of application.
Metal-free a lot of simple organic molecule is directly also obtaining good application [(a) Torii, H. in the aldol reaction; Nakadai, M.; Ishihara, K.; Saito, S.; Yamamoto, H.Angew.Chem., Int.Ed.2004,43,1983-1986. (b) Krattiger, P.; Kovasy, R.; Revell, J.D.; Ivan, S.; Wennemers, H.Org.Lett.2005,7,1101-1103. (c) Wang, W.; Lia, H.; Wang, J.Tetrahedron Lett.2005,46,5077-5079. (d) Hartikka, A.; Arvidsson, P.I.Eur.J.Org.Chem.2005,20,4287-4295. (e) Samanta, S.; Liu, J.Y.; Dodda, R.; Zhao, C.G.Org.Lett.2005,7,5321-5323. (f) Z.Tang, F.Jiang, X.Cui, L.Z.Gong, A.Q.Mi, Y.Z.Jiang, Y.D.Wu, Proc.Natl.Acad. Sci.U.S.A.2004.101,5755-5760.].Yet, the problem of these organic molecule ubiquity preparation difficulties.
Cheap natural organic molecule such as L-proline(Pro) are directly being obtained reasonable effect in the aldol reaction, and have obtained people's attention [(a) List, B. with its reaction conditions gentleness cheap and easy to get; Lerner, R.A.; Barbas, C.F., III.J.Am.Chem.Soc.2000,122,2395-2396. (b) Notz, W.; List, B.J.Am.Chem.Soc.2000,122,7386-7387. (c) List, B.; Pojarliev, P.; Castello C.Org.Lett.2001,3,573-575. (d) Sakthivel, K.; Notz, W.; Bui, T.; Barbas, C.F.III.J.Am Chem.Soc.2001.123,5260-5267.].But the L-proline(Pro) is lower at the enantioselectivity of the direct aldol addition reaction of catalysis aromatic aldehyde and ketone.
Summary of the invention
Purpose of the present invention just provides a kind of method for preparing the chiral beta-hydroxy ketone of high optical activity, and this method technology is simple, the atom utilization height, and the reaction conditions gentleness, product has good enantiomeric purity, and preparation cost is lower.
Principle of the present invention is: acetone carries out direct aldol addition, obtains chiral beta-hydroxy ketone high enantioselectivity aldehyde in the presence of chiral additives.
Technical scheme provided by the invention is: a kind of method for preparing optically active beta-hydroxy ketone, and in the presence of (S)-proline(Pro), acetone mixes the back with chiral diol or chirality diphenol and adds aldehyde, stirring reaction 8～96 hours under-20 ℃～110 ℃; The purified processing of reaction product, (as using the saturated ammonium chloride solution stopped reaction, separatory is used organic solvent extraction, merges organic phase, concentrated, resistates column chromatography) obtains chiral beta-hydroxy ketone.
The mol ratio of above-mentioned aldehyde, acetone, (S)-proline(Pro) and chiral diol or chirality diphenol is 10: 80～200: 1～4: 0.1～4.
According to the present invention, can use excessive liquid ketone as solvent.
According to the present invention, chiral diol or chirality diphenol be selected from (2R, 3R)-diethyl tartrate, (2S, 3S)-diethyl tartrate, (2R, 3R)-dimethyl tartrate, (2S, 3S)-dimethyl tartrate, (2R, 3R)-1,1 ' 4,4 '-tetraphenyl-1,2,3, the 4-butantetraol, (2S, 3S)-1,1 ' 4,4 '-tetraphenyl-1,2,3, the 4-butantetraol, (4R, 5R)-two-and (phenylbenzene hydroxymethyl)-1,3-dioxo spiro [4,5] decane, (4S, 5S)-two-(phenylbenzene hydroxymethyl)-1,3-dioxo spiro [4,5] decane, (4R, 5R)-two-(phenylbenzene hydroxymethyl)-2,2-dimethyl-1, the 3-dioxolane, (4S, 5S)-two-(phenylbenzene hydroxymethyl)-2,2-dimethyl-1, the 3-dioxolane, right amine deutero-1, the 3-glycol, (R)-1,1 '-union-2-naphthol, (S)-1,1 '-union-2-naphthol and (R)-1,1 '-union-2-naphthol or (S)-1,1 '-three of union-2-naphthol deutero-go up with six on substitution product.
According to aldehyde of the present invention is aromatic aldehyde, aryl is phenyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 2-chloro-phenyl-, 3-chloro-phenyl-, 4-chloro-phenyl-, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 4-aminomethyl phenyl, 2-p-methoxy-phenyl, 3-p-methoxy-phenyl, 4-p-methoxy-phenyl, 3,5-dichlorophenyl, 2,4-dichlorophenyl, 2,6-dichlorophenyl, Alpha-Naphthyl, betanaphthyl or 9-anthryl etc.
According to the present invention, ether, ethyl acetate, tetrahydrofuran (THF), methylene dichloride, chloroform, ethylene dichloride are used as extraction agent.
According to the present invention, chiral beta-hydroxy ketone can obtain high enantioselectivity.
The present invention is in the presence of chiral additives, the simple direct asymmetric aldol of organic molecule catalysis obtains chiral beta-hydroxy ketone with reacting high corresponding selection, have that chiral catalyst is cheap and easy to get, reaction conditions is gentle, technology is simple, raw material be simple and easy to, distinguishing feature such as low, the enantiomeric purity height of atom utilization height, cost.
Embodiment
Below in conjunction with specific embodiment technical scheme of the present invention is described further.
Embodiment 1
At one magneton, 1.5mmol (S)-proline(Pro), 1mmol (R)-1 are housed, inject 3 ml (40mmol) acetone in the test tube of 1 '-union-2-naphthol, stir 15min, then add the 5mmol phenyl aldehyde and under this temperature, continue to stir 48h at 40 ℃.Add the saturated NH of 10ml
4The Cl aqueous solution stirs 5min, with ethyl acetate extraction (15ml * 3), merges organic phase, anhydrous Na
2SO
4Drying concentrates, column chromatography (silica gel, 200-300mesh, sherwood oil: acetone (v/v)=2: 1) get (R)-4-hydroxy-4-phenyl-2-butanone, yield: 52.4%; [α]
D 20+ 55.8 (c=2.3, in CHCl
3), 91.3%ee;
1H NMR (CDCl
3, 300MHz) δ (ppm): 7.33-7.25 (m, 5H.Ph-H), 5.14-5.11 (d, J=6.7Hz, 1H, CH), 3.57 (s, 1H, OH), 2.92-2.74 (m, 2H, CH
2), 2.17 (s, 3H, CH
3);
13C NMR (CDCl
3, 300MHz) δ (ppm): 209.2,143.0,128.7,127.9,125.8,70.1,52.3,31.1; IR (KBr): v 3420 (s, OH), 3031 (w, Ph-H), 2902 (w, CH), 1708 (vs, C=O), 1602 (w, Ph-H).
Embodiment 2
At one magneton, 1.5mmol (S)-proline(Pro), 1mmol (R)-1 are housed, inject 5ml (68mmol) acetone in the test tube of 1 '-union-2-naphthol, stir 15min, then add the 5mmol phenyl aldehyde at 40 ℃ of following stirring reaction 96h at 20 ℃.Add the saturated NH of 10ml
4The Cl aqueous solution stirs 5min, with ethyl acetate extraction (15ml * 3), merges organic phase, anhydrous Na
2SO
4Drying concentrates, column chromatography (silica gel, 200-300mesh, sherwood oil: acetone (v/v)=2: 1) get (R)-4-hydroxy-4-phenyl-2-butanone, yield: 56.0%; [α]
D 20+ 54.0 (c=2.0, in CHCl
3), 88.3%ee.
Embodiment 3
At one magneton, 2.0mmol (S)-proline(Pro), 1mmol (R)-1 are housed, inject 3ml (40mmol) acetone in the test tube of 1 '-union-2-naphthol, stir 15min, then add the 5mmol phenyl aldehyde and under this temperature, continue to stir 8h at-20 ℃.Add the saturated NH of 10ml
4The Cl aqueous solution stirs 5min, with ethyl acetate extraction (15ml * 3), merges organic phase, anhydrous Na
2SO
4Drying concentrates, column chromatography (silica gel, 200-300mesh, sherwood oil: acetone (v/v)=2: 1) get (R)-4-hydroxy-4-phenyl-2-butanone, yield: 49.1%; [α]
D 20+ 53.1 (c=1.7, in CHCl
3), 86.9%ee.
Embodiment 4
0.5 mmol (S)-proline(Pro), 2mmol (R)-1 are being housed, are injecting 3ml (40mmol) acetone in the test tube of 1 '-union-2-naphthol, stirring 15min, then adding the 5mmol phenyl aldehyde and under this temperature, continue to stir 48h at 110 ℃.Add the saturated NH of 10ml
4The Cl aqueous solution stirs 5min, with ethyl acetate extraction (15ml * 3), merges organic phase, anhydrous Na
2SO
4Drying concentrates, column chromatography (silica gel, 200-300mesh, sherwood oil: acetone (v/v)=2: 1) get (R)-4-hydroxy-4-phenyl-2-butanone, yield: 51.1%; [α]
D 20+ 54.2 (c=2.2, in CHCl
3), 88.7%ee.
Embodiment 5
According to operation similar to Example 1, in a test tube that magneton is housed, inject 3ml (40mmol) acetone, with 1.5mmol (S)-proline(Pro), 1mmol (4R, 5R)-two-(phenylbenzene hydroxymethyl)-1,3-dioxo spiro [4,5] decane is made additive, at 40 ℃ of reaction 48h, addition gets (R)-4-hydroxy-4-phenyl-2-butanone, yield: 54.2% to catalysis acetone to phenyl aldehyde (5mmol); [α]
D 20+ 59.3 (c=2.7, in CHCl
3), 97.1%ee.
Embodiment 6
According to operation similar to Example 1, in a test tube that magneton is housed, inject 3ml (40mmol) acetone, with 1.5mmol (S)-proline(Pro), 0.05mmol (R)-1,1 '-union-2-naphthol is made additive, at 40 ℃ of reaction 48h, addition gets (R)-4-hydroxy-4-phenyl-2-butanone, yield: 48.7% to catalysis acetone to phenyl aldehyde (5mmol); [α]
D 20+ 49.1 (c=1.3, inCHCl
3), 80.4%ee.
Embodiment 7
According to operation similar to Example 1, in a test tube that magneton is housed, inject 3ml (40mmol) acetone, with 1.5mmol (S)-proline(Pro), 1mmol (R)-1,1 '-union-2-naphthol is made additive, and at 40 ℃ of reaction 48h, catalysis acetone is to the addition of 40 ℃ of Ortho Nitro Benzaldehydes (5mmol), obtain (R)-4-hydroxyl-4-(2 '-nitrophenyl)-2-butanone, yield: 82.3%; [α]
D 27-108.2 (c=1.2, in CHCl
3), 96.3%ee;
1H NMR (CDCl
3, 300MHz) δ (ppm): 7.95-7.39 (m, 4H, Ar-H), 5.66 (d, J=10.7Hz, 1H, CH), 3.78 (s, 1H, OH), 3.16-2.68 (m, 2H, CH
2), 2.24 (s, 3H, CH
3);
13C NMR (CDCl
3, 300MHz) δ (ppm): 208.8,147.2,138.7,134.0,128.5,128.4,124.6,65.9,51.4,30.8; IR (KBr): v 3417 (s, OH), 3075 (w, Ar-H), 2921 (w, CH), 1710 (vs, C=O), 1525,1349 (s, NO
2).
Embodiment 8
According to operation similar to Example 1, in a test tube that magneton is housed, inject 3ml (40mmol) acetone, with 1.5mmol (S)-proline(Pro), 1mmol (R)-1,1 '-union-2-naphthol is made additive, and at 40 ℃ of reaction 48h, catalysis acetone is to the addition of paranitrobenzaldehyde (5mmol) at 40 ℃, obtain (R)-4-hydroxyl-4-(4 '-nitrophenyl)-2-butanone, yield: 66%; [α]
D 16+ 49.9 (c=0.9, in CHCl
3), 73.9%ee;
1H NMR (CDCl
3, 300MHz) δ (ppm): 8.20-7.51 (m, 4H, Ar-H), 5.25 (s, 1H, CH), 3.67 (s, 1H, OH), 2.85 (d, J=6.7 Hz, 2H, CH
2), 2.21 (s, 3H, CH
3);
13C NMR (CDCl
3, 300MHz) δ (ppm): 208.6,150.2,147.4,126.6,123.9,123.9,69.2,51.8,31.1; IR (KBr): v 3443 (s, OH), 3086 (w, Ar-H), 2903 (w, CH), 1708 (vs, C=O), 1517,1348 (s, NO
2).
Embodiment 9
According to operation similar to Example 1, in a test tube that magneton is housed, inject 3ml (40mmol) acetone, with 1.5mmol (S)-proline(Pro), 1mmol (R)-1,1 '-union-2-naphthol is made additive, and at 40 ℃ of reaction 48h, catalysis acetone is to the addition of 4-chloro-benzaldehyde (5mmol) at 40 ℃, obtain (R)-4-hydroxyl-4-(4 '-chloro-phenyl-)-2-butanone, yield: 77.6%; [α]
D 27+ 53.5 (c=1.0, in CHCl
3), 88.7%ee.
1H?NMR(CDCl
3，300MHz)δ(ppm)：7.30-7.24(m，4H，Ar-H)，5.10(s，1H，CH)，3.45(s，1H，OH)，2.82-2.80(m，2H，CH
2)，2.18(s，3H，CH
3)；
13CNMR(CDCl
3，300MHz)δ(ppm)：208.4，141.2，133.3，128.7，127.1，69.7，52.6，31.7；IR(KBr)：v3430(s，OH)，3051(w，Ph-H)，2883(w，CH)，1700(vs，C＝O)，1594(w，Ar-H)。
Embodiment 10
According to operation similar to Example 1, in a test tube that magneton is housed, inject 3ml (40mmol) acetone, with 1.5mmol (S)-proline(Pro), 1 mmol (R)-1,1 '-union-2-naphthol is made additive, and at 40 ℃ of reaction 48h, catalysis acetone is to the addition of 40 ℃ of 3-bromobenzaldehydes (5mmol), obtain (R)-4-hydroxyl-4-(3 '-bromophenyl)-2-butanone, yield: 87.2%; [α]
D 16+ 48.2 (c=1.1, in CHCl
3), 90.7%ee.
1H?NMR(CDCl
3，300MHz)δ(ppm)：7.48-7.17(m，4H，Ar-H)，5.07(q，J＝6.7Hz，1H，CH)，3.73(d，J＝3.3Hz，1H，OH)，2.82-2.78(m，2H，CH
2)，2.17(s，3H，CH
3)；
13C?NMR(CDCl
3，300MHz)δ(ppm)：208.1，145.1，130.6，130.2，128.8，124.4，122.7，69.6，52.5，31.7；IR(KBr)：v?3424(s，OH)，3063(w，Ar-H)，2901(w，CH)，17?10(vs，C＝O)。
Embodiment 11
According to operation similar to Example 1, in a test tube that magneton is housed, inject 3ml (40mmol) acetone, with 1.5mmol (S)-proline(Pro), 1mmol (R)-1,1 '-union-2-naphthol is made additive, at 40 ℃ of reaction 48h, catalysis acetone is to the addition of p-bromobenzaldehyde (5mmol) at 40 ℃, obtain (R)-4-hydroxyl-4-(4 '-bromophenyl)-2-butanone, yield: 74.1%, 97.1%ee; [α]
D 27+ 48.29 (c=0.820, in CHCl
3).
1H?NMR(CDCl
3，300MHz)δ(ppm)：7.38-7.11(m，4H，Ar-H)，5.01(q，J＝8.7Hz，1H，CH)，3.36(s，1H，OH)，2.74-2.71(m，2H，CH
2)，2.11(s，3H，CH
3)；
13C?NMR(CDCl
3，300MHz)δ(ppm)：208.3，141.6，131.6，127.4，121.5，69.7，52.4，31.7；IR(KBr)：v?3450(s，OH)，3056(w，Ar-H)，2900(w，CH)，1709(vs，C＝O)。.
Embodiment 12
According to operation similar to Example 1, in a test tube that magneton is housed, inject 7.35ml (100mmol) acetone, with 1.5mmol (S)-proline(Pro), 1mmol (R)-1,1 '-union-2-naphthol is made additive, at 40 ℃ of reaction 48 h, catalysis acetone is to the addition of 1-naphthaldehyde (5mmol) at 40 ℃, obtain (R)-4-hydroxyl-4-(1 '-naphthyl)-2-butanone, yield: 61.7%, 71.3%ee; M.p.:99-101 ℃; [α]
D 25+ 72.74 (c=0.587, in CHCl
3);
1H NMR (CDCl
3, 300MHz) δ (ppm): 7.97-7.43 (m, 7H, Naph-H), 5.93 (s, 1H, CH), 3.42 (t, J=1.7 Hz, 1H, OH), 2.99-2.97 (m, 2H, CH
2), 2.21 (s, 3H, CH
3);
13C NMR (CDCl
3, 300MHz) δ (ppm): 208.6,138.1,133.8,129.9,129.1,128.1,126.3,125.6,123.1,122.8,67.3,52.0,31.7; IR (KBr): v 3358 (s, OH), 3065 (w, Ar-H), 2903 (w, CH), 1 689 (vs, C=O).
Embodiment 13
According to operation similar to Example 1, in a test tube that magneton is housed, inject 7.35ml (100mmol) acetone, with 1.5mmol (S)-proline(Pro), 1mmol (R)-1,1 '-union-2-naphthol is made additive, at 40 ℃ of reaction 48h, catalysis acetone is to the addition of 9-anthraldehyde (5mmol) at 40 ℃, obtain (R)-4-hydroxyl-4-(9 '-anthryl)-2-butanone, yield: 22.7%, 86.0%ee; M.p.:107-109 ℃; [α]
D 25-53.88 (c=0.232, in CHCl
3);
1H NMR (CDCl
3, 300 MHz) δ (ppm): 8.63-7.42 (m, 9H, Naph-H), 6.79 (d, J=11.3,1H, CH), 3.46 (s, 1H, OH), 3.78-3.68 (m, 1H, CH
2), 2.93-2.87 (m, 1H, CH
2), 2.26 (s, 3H, CH
3);
13C NMR (CDCl
3, 300MHz) δ (ppm): 209.1,133.2,132.3,130.1,129.9,129.1,126.6,125.6,67.6,51.7,32.3; IR (KBr): v 3421 (s, OH), 3051 (w, Ar-H), 2928 (w, CH), 1 700 (vs, C=O).
Embodiment 14
According to operation similar to Example 1, in a test tube that magneton is housed, inject 3ml (40mmol) acetone, with 1.5mmol (S)-proline(Pro), 1mmol (R)-1,1 '-union-2-naphthol is made additive, at 40 ℃ of reaction 48h, catalysis acetone is to the addition of aubepine (5mmol) at 40 ℃, obtain (R)-4-hydroxyl-4-(4 '-methoxyl group)-2-butanone, yield: 26.8%, 67.6%ee; [α]
D 16+ 46.32 (c=0.380, in CHCl
3);
1H NMR (CDCl
3, 300MHz) δ (ppm): 7.21-6.79 (m, 4H, Ar-H), 5.17 (q, J=10.0Hz, 1H, CH), 3.73 (s, 1H, OCH
3), 3.49 (s, 1H, OH), 2.87-2.56 (m, 2H, CH
2), 2.12 (s.3H, CH
3);
13C NMR (CDCl
3, 300 MHz) and δ (ppm): 208.4,158.8,135.1,127.0,114.0,70.0,55.9,52.7,31.6; IR (KBr): v 3426 (s, OH), 3001 (w, Ar-H), 2958 (w, CH), 1709 (vs, C=O), 1612 (w, Ar-H), 1248,1032 (s, O-CH
3).
Claims (4)
1. method for preparing optically active beta-hydroxy ketone is characterized in that: in the presence of (S)-proline(Pro), acetone mixes the back with chiral diol or chirality diphenol and adds aldehyde, stirring reaction 8～96 hours under-20 ℃～110 ℃; The purified processing of reaction product obtains chiral beta-hydroxy ketone.
2. method according to claim 1 is characterized in that: the mol ratio of aldehyde, acetone, (S)-proline(Pro) and chiral diol or chirality diphenol is 10: 80～200: 1～4: 0.1～4.
3. method according to claim 1 and 2, it is characterized in that: chiral diol or chirality diphenol are selected from (2R, 3R)-diethyl tartrate, (2S, 3S)-diethyl tartrate, (2R, 3R)-dimethyl tartrate, (2S, 3S)-dimethyl tartrate, (4R, 5R)-two-(phenylbenzene hydroxymethyl)-1,3-dioxo spiro [4,5] decane, (4S, 5S)-two-and (phenylbenzene hydroxymethyl)-1,3-dioxo spiro [4,5] decane, (4R, 5R)-two-(phenylbenzene hydroxymethyl)-2,2-dimethyl-1, the 3-dioxolane, (4S, 5S)-two-(phenylbenzene hydroxymethyl)-2,2-dimethyl-1, the 3-dioxolane, (R)-1,1 '-union-2-naphthol or (S)-1,1 '-union-2-naphthol.
4. method according to claim 3, it is characterized in that: aldehyde is aromatic aldehyde, aryl is phenyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 2-chloro-phenyl-, 3-chloro-phenyl-, 4-chloro-phenyl-, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 4-aminomethyl phenyl, 2-p-methoxy-phenyl, 3-p-methoxy-phenyl, 4-p-methoxy-phenyl, 3,5-dichlorophenyl, 2,4-dichlorophenyl, 2,6-dichlorophenyl, Alpha-Naphthyl, betanaphthyl or 9-anthryl.
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Non-Patent Citations (6)
| Title |
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| Proline-Catalyzed Direct Asymmetric Aldol reactions. List，B.etc.J.Am.Chem.Soc.,Vol.122 No.10. 2000 |
| Proline-Catalyzed Direct Asymmetric Aldol reactions. List，B.etc.J.Am.Chem.Soc.,Vol.122 No.10. 2000 * |
| S－脯氨酸催化丙酮与2，2‘-二甲基丙醛不对称直接羫醛缩合反应过渡态的理论研究. 樊建芬等.化学学报，第63卷第8期. 2005 |
| S－脯氨酸催化丙酮与2，2‘-二甲基丙醛不对称直接羫醛缩合反应过渡态的理论研究. 樊建芬等.化学学报，第63卷第8期. 2005 * |
| 有机小分子催化的不对称直接aldol反应. 唐卓.四川大学硕士学位论文. 2003 |
| 有机小分子催化的不对称直接aldol反应. 唐卓.四川大学硕士学位论文. 2003 * |
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