L-脯氨酸衍生物手性催化剂的合成及其催化不对称直接Aldol反应，Michael加成反应
|
摘要
不对称有机催化已经迅速发展成一个有机化学领域的重要组成部分。有机小分子催化剂的出现带来了一个新的催化模式,此类催化反应不但可以降低成本,节约时间和能源,而且具有操作简便、高效、选择性好和优于传统合成方法等特点,这些优势让有机小分子催化备受关注。毫无疑问,脯氨酸及其衍生物是有机小分子催化的重要组成部分。
Aldol反应是一类重要的形成C-C键的反应,是不对称有机催化反应领域的一个重要组成部分,目前脯氨酰胺已经成为这个领域的研究热点之一,但是,我们不难发现人多数脯氨酰胺催化剂不仅结构复杂而且成本昂贵。此外,这类催化剂需要高的催化剂用量(10-30 mol%)和大量的酮用量(大于10equiv.)极大的限制了他们的工业应用。
为了提供一种简便,便宜,高效的途径得到Aldol产物,同时为了实现在工业上的应用,本论文设计合成了两类简单便宜的脯氨酰胺类有机小分子催化剂,并用来催化不同类型的酮和各种不同取代芳香醛的直接不对称Aldol反应。在研究中我们发现,脯氨酰胺1a-1e和2a-2d都能高效的催化不对称Aldol反应,只需要5 mol%催化剂用量和4equiv酮用量,其产物的dr值达到99:1,ee值达到99%,产率达到99%。结果表明不管是碳环还是芳环等环状结构,在形成Aldol产物的过程中都起到了积极的作用。另外,值得提出的是,催化剂2a在不需要固载的情况下通过简单的方法可以进行回收,重复使用至少5次后催化活性没有明显降低。同时,我们发现这种价格低廉,简单和可再生的催化剂能够有效地用于扩大反应中,使得此类催化剂在工业上的应用成为可能。
Michael加成反应也是有机合成中最为常用的一类形成C-C键的反应,有机小分子催化不对称Michael加成已成为国内外不对称催化研究中的一个热点课题。其中脯氨酸及其衍生物催化手性Michael加成取得了卓越的成绩,但是,我们发现此类催化大多数是在有机溶剂中进行的,根据绿色化学的思想,能够在水相中发生反应并且具有高的对映选择性的催化体系在现代化学里仍很有限,而发展这些高效的催化体系必将成为人们不断追寻的目标。
本论文设计合成了一类不同链长的简单脯氨醇硅烷基醚类有机小分子催化剂,并用于催化不对称Michael加成反应,研究结果表明不同链长的催化剂在有机相和水相中表现出不同的催化活性,其中4a在有机相里表现出最好的催化活性,在水相中添加酸性添加剂的情况下4c表现出最好的催化活性,符合绿色化学的发展要求。
Asymmetric organocatalysis has emerged as a rapidly growing and important field in organic chemistry. The search for small molecules that are able to act as catalysts in enantioselective transformations has received extensive attention during the last decade, and small molecules as organocatalysis brought the prospect of a complementary mode of catalysis, with the potential for savings in cost, time and energy, an easier experimental procedure, and reductions in chemical waste. Not surprisingly, proline and derivatives have become an important part of the small molecules catalytic.
Aldol reaction constitutes one of the immensely investigated amongst carbon-carbon bond forming reactions in the realm of organocatalysis. These compounds are generally prolinamide derivatives that differ in the nature of the amine component attached to the carboxylic functionality of proline, and generally contain additional stereogenic center and hydrogen-bonding site. Therefore, these catalysts are not only complex but also expensive as a rule. One of the major limitations using organocatalyst catalyzed reactions is the high catalyst loading (10-30 mol%) generally required to complete the transformations in large equivalents ketone in reasonable timescales. This will raise a cost concern when large amounts of chiral materials are used for a large-scale synthesis in industrial applications.
With the aim to discover a simple, cheap and efficient route to highly enantiomerically enriched anti-aldol products catalyzed by simple prolinamides and offer great possibility for applications in industry, we prepared prolinamines 1a-1e and 2a-2d. It is shown that prolinamides 1a-e and 2a-d exhibited great catalytic activity in the asymmetric aldol reaction in m-xylene at-20℃only with 5 mol% catalyst loading in 4 equivalents ketone. And afforded aldol products in a high diastereoselectivity (up to anti/syn 99:1) and enantioselectivity (99%) and significantly enhanced reaction yield (99%). The catalyst 2a can be easily recovered and reused, and without significant decrease of enantioselectivity was observed for five cycles. Furthermore, this cheap, simple and recyclable catalyst can be efficiently used in large-scale reactions with the enantioselectivities being maintained at the same level, which offers a great possibility for application in industry.
Micheal reaction is also recognized as one of the most powerful carbon-carbon bond-forming reactions in modern organic synthesis, and organic small molecules catalytic asymmetrical Michael addition reaction have become a hot topic in the domestic and foreign in asymmetrical catalytic. However, this organocatalytic processes have typically been carried out in organic solvents, such as DMSO, DMF, or in mixed aqueous organic solvent, under mild conditions. Therefore, highly efficient catalytic system, which gives high enantioselectivity for a broad range of substrates in water is still limited and develop the excellent catalytic system will be a goal of continue to pursue.
In this paper, a kind of different links of diphenylperhydroindolinol silyl ethers was synthesized from proline, and they were evaluated for asymmetric Michael reaction. The results show that different links of catalyst performance of the different catalytic activity in organic solvents and the water. Catalyst 4a is the best in the organic solvents and 4c is the best in the water.
Aldol反应是一类重要的形成C-C键的反应,是不对称有机催化反应领域的一个重要组成部分,目前脯氨酰胺已经成为这个领域的研究热点之一,但是,我们不难发现人多数脯氨酰胺催化剂不仅结构复杂而且成本昂贵。此外,这类催化剂需要高的催化剂用量(10-30 mol%)和大量的酮用量(大于10equiv.)极大的限制了他们的工业应用。
为了提供一种简便,便宜,高效的途径得到Aldol产物,同时为了实现在工业上的应用,本论文设计合成了两类简单便宜的脯氨酰胺类有机小分子催化剂,并用来催化不同类型的酮和各种不同取代芳香醛的直接不对称Aldol反应。在研究中我们发现,脯氨酰胺1a-1e和2a-2d都能高效的催化不对称Aldol反应,只需要5 mol%催化剂用量和4equiv酮用量,其产物的dr值达到99:1,ee值达到99%,产率达到99%。结果表明不管是碳环还是芳环等环状结构,在形成Aldol产物的过程中都起到了积极的作用。另外,值得提出的是,催化剂2a在不需要固载的情况下通过简单的方法可以进行回收,重复使用至少5次后催化活性没有明显降低。同时,我们发现这种价格低廉,简单和可再生的催化剂能够有效地用于扩大反应中,使得此类催化剂在工业上的应用成为可能。
Michael加成反应也是有机合成中最为常用的一类形成C-C键的反应,有机小分子催化不对称Michael加成已成为国内外不对称催化研究中的一个热点课题。其中脯氨酸及其衍生物催化手性Michael加成取得了卓越的成绩,但是,我们发现此类催化大多数是在有机溶剂中进行的,根据绿色化学的思想,能够在水相中发生反应并且具有高的对映选择性的催化体系在现代化学里仍很有限,而发展这些高效的催化体系必将成为人们不断追寻的目标。
本论文设计合成了一类不同链长的简单脯氨醇硅烷基醚类有机小分子催化剂,并用于催化不对称Michael加成反应,研究结果表明不同链长的催化剂在有机相和水相中表现出不同的催化活性,其中4a在有机相里表现出最好的催化活性,在水相中添加酸性添加剂的情况下4c表现出最好的催化活性,符合绿色化学的发展要求。
Asymmetric organocatalysis has emerged as a rapidly growing and important field in organic chemistry. The search for small molecules that are able to act as catalysts in enantioselective transformations has received extensive attention during the last decade, and small molecules as organocatalysis brought the prospect of a complementary mode of catalysis, with the potential for savings in cost, time and energy, an easier experimental procedure, and reductions in chemical waste. Not surprisingly, proline and derivatives have become an important part of the small molecules catalytic.
Aldol reaction constitutes one of the immensely investigated amongst carbon-carbon bond forming reactions in the realm of organocatalysis. These compounds are generally prolinamide derivatives that differ in the nature of the amine component attached to the carboxylic functionality of proline, and generally contain additional stereogenic center and hydrogen-bonding site. Therefore, these catalysts are not only complex but also expensive as a rule. One of the major limitations using organocatalyst catalyzed reactions is the high catalyst loading (10-30 mol%) generally required to complete the transformations in large equivalents ketone in reasonable timescales. This will raise a cost concern when large amounts of chiral materials are used for a large-scale synthesis in industrial applications.
With the aim to discover a simple, cheap and efficient route to highly enantiomerically enriched anti-aldol products catalyzed by simple prolinamides and offer great possibility for applications in industry, we prepared prolinamines 1a-1e and 2a-2d. It is shown that prolinamides 1a-e and 2a-d exhibited great catalytic activity in the asymmetric aldol reaction in m-xylene at-20℃only with 5 mol% catalyst loading in 4 equivalents ketone. And afforded aldol products in a high diastereoselectivity (up to anti/syn 99:1) and enantioselectivity (99%) and significantly enhanced reaction yield (99%). The catalyst 2a can be easily recovered and reused, and without significant decrease of enantioselectivity was observed for five cycles. Furthermore, this cheap, simple and recyclable catalyst can be efficiently used in large-scale reactions with the enantioselectivities being maintained at the same level, which offers a great possibility for application in industry.
Micheal reaction is also recognized as one of the most powerful carbon-carbon bond-forming reactions in modern organic synthesis, and organic small molecules catalytic asymmetrical Michael addition reaction have become a hot topic in the domestic and foreign in asymmetrical catalytic. However, this organocatalytic processes have typically been carried out in organic solvents, such as DMSO, DMF, or in mixed aqueous organic solvent, under mild conditions. Therefore, highly efficient catalytic system, which gives high enantioselectivity for a broad range of substrates in water is still limited and develop the excellent catalytic system will be a goal of continue to pursue.
In this paper, a kind of different links of diphenylperhydroindolinol silyl ethers was synthesized from proline, and they were evaluated for asymmetric Michael reaction. The results show that different links of catalyst performance of the different catalytic activity in organic solvents and the water. Catalyst 4a is the best in the organic solvents and 4c is the best in the water.
引文
[1]林国强,陈耀全,陈新滋,李月明.手性合成—不对称反应及其应用.科学出版社：北京,2000.pp1-40
[2]尤天耙.手性化合物的现代研究方法.中国科学技术大学出版社,合肥,1993,pp 6-10
[3]张生勇,郭建全.不对称催化反应—原理及在有机合成中的应用,北京：科学出版社,2002
[4]周维善,庄治平,不对称反应,北京：科学出版社,1997
[5]殷元骐,蒋耀忠,不对称催化反应进展,北京：科学出版社,2000
[6]Dalko, P. L.; Moisan, L. Enantioselective organocatalysis. Angew. Chem. Int. Ed,2001,40, 3726-3748
[7]Dalko, P. L.; Moisan, L. In the golden age of organocatalysis. Angew. Chem., Int. Ed.2004, 43,5138-5175
[8]list, B. Proline-catalyzed asymmetric reactions. Tetrahedron.2002,58,5573-5590
[9]李经纬,徐利文,夏春谷.脯氨酸催化剂在不对称反应中的研究进展.有机化学.2004,24,23-28
[10]魏晓芳.光学活性脯氨酸催化的不对称有机合成反应.有机化学.2005,25,1619-1626
[11]Tang, Z.; Jiang, F.; Yu, L.-T.; Cui, X.; Gong, L.-Z.; Mi, A.-Q.; Jiang, Y.-Z.; Wu, Y.-D. Novel small organic molecules for a highly enantioselective direct aldol reaction. J. Am. Chem. Soc. 2003,125,5262-5263
[12]Tang, Z.; Yang, Z.-H.; Chen, X.-H.; Cun, L.-F.; Mi, A.-Q.; Jiang, Y.-Z.; Gong, L.-Z. A highly efficient organocatalyst for direct aldol reactions of ketones with aldedydes. J. Am. Chem. Soc.2005,127,9285-9289
[13]Tang, Z.; Jiang, F.; Cui, X.; Gong, L.-Z.; Mi, A.-Q.; Jiang, Y.-Z.; Wu, Y.-D. Enantioselective direct aldol reactions catalyzed by L-prolinamide derivatives. Proc. Natl. Acad. Sci. U.S.A. 2004,101,5755-5760
[14]Tang, Z.; Jiang, F.; Cui, X.; Gong, L.-Z.; Mi, A.-Q.; Jiang, Y.-Z.; Wu, Y.-D. Enantioselective direct aldol reactions catalyzed by L-prolinamide derivatives. PNAS, April 20,2004,101,16, 5755-5760
[15]Guo, H.-M.; Cun, L.-F.; Gong, L.-Z.; Mi, A.-Q.; Jiang, Y.-Z. Asymmetric direct aldol reaction catalyzed by an L-prolinamide derivative:Considerable improvement of the catalytic efficiency in the ionic liquid. Chem. Commun.2005,1450-1452
[16]Berkessel, A.; Koch, B.; Lex, J. Proline-derived N-sulfonylcarboxamides:Readily available, highly enantioselective and versatile catalysts for direct aldol reactions. Adv. Synth. Catal. 2004,346,1141-1146
[17]Cobb, A. J. A.; Shaw, D. M.; Longbottom. D. A.; Ley, S. V. Organocatalysis with proline derivatives:Improved catalysts for the asymmetric Mannich, nitro-Michael and aldol reactions. Org. Biomol. Chem.2005.3,84-96
[18]Yang, H.; Carter, R. G. N-(p-Dodecylphenylsulfonyl)-2-pyrrolidinecarboxamide:A practical proline mimetic for facilitating enantioselective aldol reactions. Org. Lett,2008,10, 4649-4652
[19]Zhang, S.-P.; Fu. X.-K.; Fu, S.-D.; Pan, J.-F. Highly efficient 4-phenoxy substituted organocatalysts derived from N-prolylsulfonamide for the asymmetric direct aldol reaction on water. Catalysis Communications.2009,10,401-405
[20]Fu, S.-D.; Fu, X.-K.; Zhang, S.-P.; Zou, X.-C.; Wu, X.-J.; Highly diastereo- and enantioselective direct aldol reactions by 4-tert-butyldimethylsiloxy-substituted organocatalysts derived from N-prolylsulfonamides in water. Tetrahedron:Asymmetry.2009, 20,2390-2396.
[21]Gryko, D.; Lipiriski, R. L-prolinethioamides-efficient organocatalysts for the direct asymmetric aldol reaction. Adv. Synth. Catal.2005,347,1948-1952
[22]Almasi, D.; Alonso, D. A.; Najeraa, C. Prolinamides versus prolinethioamides as recyclable catalysts in the enantioselective solvent-free inter-and intramolecular aldol reactions, Adv. Synth. Catal.2008,350,2467-2472
[23]Samanta, S.; Liu, J. Y.; Dodda, R.; Zhao C. G. C2-symmetric bisprolinamide as a highty efficient catalyst for direct aldol reaction. Org. Lett.2005,7,5321-5323.
[24]Chen, J.-R.; Lu, H.-H.; Li, X.-Y.; Cheng, L.; Wan, J.; Xiao, W.-J. Readily tunable and bifunctional l-prolinamide derivatives:design and application in the direct enantioselective aldol reactions. Org. Lett.2005,7,4543-4545
[25]Chen, J.-R.; Li, X.-Y,; Xing, X.-N.; Xiao, W.-J. Highly stereoselective palladium-catalyzed dithiocarbonylation of propargylic mesylates with thiols and carbon monoxide. J. Org. Chem. 2005,70,1802-1807
[26]Yang, Y.; He, Y.-H.; Guan, Z.; Huang, W.-D. A highly efficient large-scale asymmetric direct intermolecular aldol reaction employing L-prolinamide as a recoverable catalyst. Adv. Synth. Catal.2010,352,2579-2587
[27]Fu, Y.-Q.; Li, Z.-C.; Ding, L.-N.; Tao, J.-C.; Zhang, S.-H.; Tang, M.-S. Direct asymmetric aldol reaction catalyzed by simple prolinamide phenols. Tetrahedron:Asymmetry.2006,17, 3351-3357
[28]Chimni, S. S.; Mahajan, D. Small organic molecule catalyzed enantioselective direct aldol reaction in water. Tetrahedron:Asymmetry.2006,17,2108-2119
[29]He, L.; Tang, Z.; Cun, L.-F.; Mi, A.-Q.; Jiang, Y.-Z.; Gong, L.-Z. L-Proline amide-catalyzed direct asymmetric aldol reaction of aldehydes with chloroacetone. Tetrahedron.2006,62, 346-351
[30]Zhang, S.-P.; Fu, X.-K.; Fu, S.-D. Rationally designed 4-phenoxy substituted prolinamide phenols organocatalyst for the direct aldol reaction in water. Tetrahedron Letters 2009,50, 1173-1176
[31]Sato, K.; Kuriyama, M.; Shimazawa, R.; Morimoto, T.; Kakiuchi, K.; Shirai, R. Direct asymmetric aldol reactions catalyzed by L-proline-2,4,6-trinitroanilide. Tetrahedron Letters 2008,49,2402-2406
[32]Moorthy, J. N.; Saha, S. Highly diastereo- and enantioselective aldol Reactions in common organic solvents using N-arylprolinamides as organocatalysts with enhanced acidity. DOI:10.1002/ejoc.200800960
[33]Chen, J.-R.; An, X.-L.; Zhu, X.-Y.; Wang, X.-F.; Xiao, W.-J. Rational combination of two privileged chiral backbones:highly efficient organocatalysts for asymmetric direct aldol reactions between aromatic aldehydes and acylic ketones, J. Org. Chem.2008,73,6006-6009
[34]Agarwal, J.; Peddinti, R. K. Highly efficient and solvent-free direct aldol reaction catalyzed by glucosamine-derived prolinamide. Tetrahedron:Asymmetry.2010,21,1906-1909
[35]List, B.; Lerner, R. A.; Barbas, C F Ⅲ. Proline-catalyzed direct asymmetric aldol reactions. J. Am. Chem. Soc.2000,122,2395-23961
[36]List, B.; Pojarliev, P.; Martin, H. J. Efficient proline-catalyzed michael additions of unmodified ketones to nitro olefins. Org. Lett.2001,3,2423-24251
[37]Betancort, J. M.; Sakthivel, K. R.; Thayumanavan. Tetrahedron Lett.2001,42,4441-44441
[38]Mase, N.; Thayumanavan, R.; Tanaka, F. Direct asymmetric organocatalytic michael reactions of α,α-disubstituted aldehydes with β-nitrostyrenes for the synthesis of quaternary carbon-containing products. Org. Lett.2004,6,2527-2530
[39]Chi, Y.; Gellman, S. H. Diphenylprolinol methyl ether:A highly enantioselective catalyst for michael addition of aldehydes to simple enones. Org. Lett.2005,7,4253-4255
[40]Hayashi, Y.; Gotoh, H.; Hayashi, T.; Shoji, M. Angew. Chem. Int. Ed.2005,44,4212
[41]Zhu, S.-L.; Yu, S.-Y.; Ma, D. Highly efficient catalytic system for enantioselective michael addition of aldehydes to nitroalkenes in water. Angew. Chem. Int. Ed.2008,47,545-548
[42]Hayashi, Y.; Itoh, T.; Ohkubo, M.; Ishikawa, H. Asymmetric michael reaction of acetaldehyde catalyzed by diphenylprolinol silyl ether. Angew. Chem. Int. Ed.2008,47, 4722-4724
[43]Ren-Shi Luo, Jiang Weng, Hui-Bing Ai, Gui Lu, and Albert S. C. Chana, Highly efficient asymmetric michael reaction of aldehydes to nitroalkenes with diphenylperhydroindolinol silyl ethers as organocatalysts. Adv. Synth. Catal.2009,351,2449-2459
[44]Berkessel A, Groger H. Books on organocatalysis:Asymmetric organocatalysis:From biomimetic concepts to applications in asymmetric synthesis. Eds Wiley-VCH:Weinheim, 2005
[45]Dalko P. I. Enantioselective organocatalysis:Reactions and experimental procedures. Ed Wiley-VCH:Weinheim,2007
[46]Tian, S. K.; Chen, Y. G.; Hang, J. F.; Tang, L.; McDaid, P.; Deng, L. Asymmetric organic catalysis with modified cinchona alkaloids. Acc Chem Res,2004,37,621-631
[47]List, B. Introduction:Organocatalysis. Chem Rev,2007,107,5413-5415
[48]Enders, D.; Grondal, C.; Huttl, R. M. Asymmetric organocatalytic domino reactions. Angew Chem. Int. Ed.2007,46,1570-1581
[49]Dondoni, A.; Massi, A. Asymmetric organocatalysis:From infancy to adolescence. Angew Chem. Int. Ed.2008,47,4638-4660
[50]MacMillan, D. W. C. The advent and development of organocatalysis. Nature,2008,455, 304-308
[51]Movassaghi, M.; Jacobsen, E. N. The simplest enzyme. Science,2002,298,1904-1905
[52]Notz, W.; Tanaka, F.; Barbas, Ⅲ CF. Enamine-based organocatalysis with proline and diamines:The development of direct catalytic asymmetric aldol, mannich, michael, and diels-alder reactions. Acc. Chem. Res,2004,37,580-591
[53]Kazmaier, U. Amino acids—valuable organocatalysts in carbohydrate synthesis. Angew Chem. Int. Ed,2005,44,2186-2188
[54]Schetter, B.; Mahrwald, R. Modern aldol methods for the total synthesis of polyketides. Angew. Chem. Int. Ed.2006,45,7506-7525
[55]List, B. The ying and yang of asymmetric aminocatalysis. Chem. Commun,2006,8,819-824
[56]Geary, L. M.; Hultin, P. G. The state of the art in asymmetric induction:the aldol reaction as a case study. Tetrahedron:Asymmetry,2009,20,131-173
[57]Dalko, P. L.; Moisan, L. In the golden age of organocatalysis. Angew. Chem. Int. Ed.2004, 43,5138-5175
[58]Li, C.-J. Organic reactions in aqueous media with a focus on carbon-carbon bond formations: a decade update. Chem. Rev.2005,105,3095-3165
[59]Palomo, C.; Oiarbide, M.; Garca, J. M. Current progress in the asymmetric aldol addition reaction. Chem. Soc. Rev.2004,33,65-75
[60]Alcaide, B.; Almendros, P. The direct catalytic asymmetric cross-aldol reaction of aldehydes. Angew. Chem. Int. Ed,2003,42,858-860
[61]List, B.; Lerner, R. A.; Barbas. Ⅲ CF. Proline-catalyzed direct asymmetric aldol reaction (List and co-workers). J. Am. Chem. Soc.2000,122.2395-2396
[62]Notz, W.; List, B. Catalytic asymmetric synthesis of anti-1,2-diols. J. Am. Chem. Soc.2000, 122,7386-7387
[63]Bahmanyar, S.; Houk, K. N.; Martin, H. J.; List, B. Quantum mechanical predictions of the stereoselectivities of proline-catalyzed asymmetric intermolecular aldol reactions. J. Am. Chem. Soc.2003,125,2475-2479
[64]List, B.; Hoang, L.; Martin, H. J. New mechanistic studies on the proline-catalyzed aldol reaction. Proc. Natl. Acad. Sci. USA.2004,101,5839-5842
[65]Mukherjee, S.; Yang, J. W.; Hoffmann, S.; List, B. Asymmetric enamine catalysis. Chem. Rev.2007,107,5471-5569
[66]Chen, J.-R.; Liu, X.-P.; Zhu, X.-Y.; Li, L.; Qiao, Y.-F.; Zhang. J.-M.; Xiao, W.-J. Organocatalytic asymmetric aldol reaction of ketones with isatins:straightforward stereoselective synthesis of 3-alkyl-3-hydroxyindolin-2-ones. Tetrahedron,2007,63, 10437-10444
[67]Huang, W.-P.; Chen, J.-R.; Li, X.-Y.; Cao, Y.-J.; Xiao, W.-J. Asymmetric organocatalytic direct aldol reactions of cyclohexanone with aldehydes in brine. Can. J. Chem.2007,85, 208-213
[68]Guizzetti, S.; Benaglia, M.; Raimondi, L.; Celentano, G. Enantioselective direct aldol reaction "on water" promoted by chiral organic catalysts. Org. Lett.2007,9,1247-1250
[69]Guillena, G.; Najera, C.; Viozquez, S. F. N-Tosyl-(Sa)-binam-L-prolinamide as highly efficient bifunctional organocatalyst for the general enantioselective solvent-free aldol reaction. Synlett.2008,19,3031-3035
[70]Guillena, G.; Hita, M. D. C.; Najera, C.; Vioquez, S. F. A highly efficient solvent-free asymmetric direct aldol reaction organocatalyzed by recoverable (S)-binam-L-prolinamides. ESI-MS evidence of the enamine-iminium formation. J. Org. Chem.2008,73,5933-5943
[71]Wang, C.; Jiang, Y.; Zhang, X.-X.; Huang, Y.; Li, B.-G.; Zhang, G.-L. Rationally designed organocatalyst for direct asymmetric aldol reaction in the presence of water. Tetrahedron Lett. 2007,48,4281-4285
[72]Zhao, J.-P.; He, L.; Jiang, J.; Tang, Z.; Cun, L.-F.; Gong, L.-Z. Organo-catalyzed highly diastereo- and enantio-selective direct aldol reactions in water. Tetrahedron Lett.2008,49, 3372-3375
[73]Vishnumaya, M, R.; Singh, V. K. Highly efficient small organic molecules for enantioselective direct aldol reaction in organic and aqueous media. J. Org. Chem.2009,74, 4289-4297
[74]Chen, F.; Huang, S.; Zhang, H.; Liu, F.; Peng, Y. Proline-based dipeptides with two amide units as organocatalyst for the asymmetric aldol reaction of cyclohexanone with aldehydes. Tetrahedron.2008,64,9585-9591
[75]Moorthy, J. N.; Saha, S. Highly diastereo- and enantioselective aldol reactions in common organic solvents using N-arylprolinamides as organocatalysts with enhanced acidity. Eur. J. Org. Chem.2009,5,739-748
[76]Chimni. S. S.; Singh, S.; Mahajan, D. Protonated (S)-prolinamide derivatives—water compatible organocatalysts for direct asymmetric aldol reaction. Tetrahedron:Asymmetry. 2008,19,2276-2284
[77]Aratake, S.; Itoh, T.; Okano, T.; Nagae, N.; Sumiya, T.; Shoji, M.; Hayashi, Y. Highly diastereo- and enantioselective direct aldol reactions of aldehydes and ketones catalyzed by siloxyproline in the presence of water. Chem. Eur. J.2007,13,10246-10256
[78]Aratake, S.; Itoh, T.; Okano, T.; Usui, T.; Shoji, M.; Hayashi, Y. Small organic molecule in enantioselective, direct aldol reaction "in water". Chem. Commun.2007,24,2524-2526
[79]Hayashi, Y.; Aratake, S.; Itoh, T.; Okano, T.; Sumiya, T.; Shoji, M. Dry and wet prolines for asymmetric organic solvent-free aldehyde-aldehyde and aldehyde-ketone aldol reactions. Chem. Commun.2007,9,957-959
[80]Hayashi, Y.; Aratake, S.; Okano, T.; Takahashi, J.; Sumiya, T.; Shoji, M. Combined Proline-Surfactant Organocatalyst for the Highly Diastereo- and Enantioselective Aqueous Direct Cross-Aldol Reaction of Aldehydes. Angew. Chem. Int. Ed.2006,45,5527-5529
[81]Tang, Z.; Jiang, F.; Yu, L.-T.; Cui, X.; Gong, L.-Z.; Qiao, A.; Jiang, Y.-Z.; Wu, Y.-D. Novel Small Organic Molecules for a Highly Enantioselective Direct Aldol Reaction. J. Am. Chem. Soc.2003,125,5262-5263
[82]Tang, Z.; Jiang, F.; Yu, L.-T.; Cui, X.; Gong, L.-Z.; Mi, A.-Q.; Jiang, Y.-Z.; Wu, Y.-D. Proc. Natl. Acad. Sci. USA.2004,101,5775
[83]Tang, Z.; Yang, Z.-H.; Cun, L.-F.; Gong, L.-Z.; Mi, A.-Q.; Jiang, Y.-Z. Small peptides catalyze highly enantioselective direct aldol reactions of aldehydes with hydroxyacetone: Unprecedented regiocontrol in aqueous media. Org. Lett.2004,6,2285-2287
[84]Tang, Z.; Yang, Z.-H.; Chen, X.-H.; Cun, L.-F.; Mi, A.-Q.; Jiang, Y.-Z.; Gong, L.-Z. A highly efficient organocatalyst for direct aldol reactions of ketones with aldedydes. J. Am. Chem. Soc.2005,127,9285-9289
[85]He, L.; Tang, Z.; Cun. L.-F.; Mi, A.-Q.; Jiang, Y.-Z.; Gong, L.-Z. Tetrahedron.2005,62, 346
[86]Chen, J.-R.; Lu, H.-H.; Li, X.-Y.; Cheng, L.; Wan, J.; Xiao, W.-J. Readily Tunable and Bifunctional 1-Prolinamide Derivatives:Design and Application in the Direct Enantioselective Aldol Reactions. Org. Lett.2005,7,4543-4545
[87]Chen, J.-R.; Li, X.-Y.; Xing, X.-N.; Xiao, W.-J. Sterically and electronically tunable and bifunctional organocatalysts:Design and application in asymmetric aldol reaction of cyclic ketones with aldehydes. J. Org. Chem.2006,71,8198-8202
[88]Zhang, S. P.; Fu, X. K.; Fu, S. D.; Pan, J. F. Highly efficient 4-phenoxy substituted organocatalysts derived from N-prolylsulfonamide for the asymmetric direct aldol reaction on water. Cat. Commun,2009,10,401-405
[89]Zhang, S. P.; Fu, X. K.; Fu, S. D. Rationally designed 4-phenoxy substituted prolinamide phenols organocatalyst for the direct aldol reaction in water. Tetrahedron Lett.2009,50, 1173-1176
[90]Fu, S. D.; Fu, X. K.; Zhang, S. P.; Zou, X. C.; Wu, X. J. Highly diastereo- and enantioselective direct aldol reactions by 4-tert-butyldimethylsiloxy substituted organocatalysts derived from N-prolylsulfonamides in water. Tetrahedron:Asymmetry. 2009,20,2390-2396
[91]Wu, X. Y.; Jiang, Z. Q.; Shen, H. M.; Lu, Y. X. Highly efficient threonine-derived organocatalysts for direct asymmetric aldol reactions in water. Adv. Synth. Catal.2007,349, 812
[92]Qian, Y. B.; Zheng, X.; Wang, Y. M. A green and efficient asymmetric aldol reaction catalyzed by a chiral anion modified ionic liquid. Eur. J. Org. Chem.2010,3672-3677
[93]Mase, N.; Noshiro, N.; Mokuya, A.; Takabea, K. Adv. Effect of long chain fatty acids on organocatalytic aqueous direct aldol reactions. Synth. Catal.2009,351,2791-2796
[94]Rodriguez, B.; Bruckmann, A.; Bolm, C. A highly efficient asymmetric organocatalytic aldol reaction in a ball mill. Chem. Eur. J.2007,13,4710-4722
[95]Ramasastry, S. S. V.; Zhang, H.; Tanaka, F.; Barbas Ⅲ CF. Direct catalytic asymmetric synthesis of anti-1,2-Amino alcohols and syn-1,2-diols through organocatalytic anti-mannich and syn-aldol reactions. J. Am. Chem. Soc.2007,129,288-289
[96]Betancort, J. M.; Barbas, C. F. Ⅲ. Catalytic direct asymmetric michael reactions:Taming naked aldehyde donors. Org. Let.2001,3,3737-3740
[97]Alexakis, A.; Andrey, O. Diamine-catalyzed asymmetric michael additions of aldehydes and ketones to nitrostyrene. Org. Lett.2002,4,3611-3614
[98]Hayashi, Y.; Gotoh, H.; Hayashi, T.; Shoji, M. Diphenylprolinol silyl ethers as efficient organocatalysts for the asymmetric michael reaction of aldehydes and nitroalkenes. Angew. Chem. Int. Ed.2005,44,4212-4215
[99]Andrey, O.; Alexakis, A.; Tomassini, A.; Bernardinelli, G. The use of N-alkyl-2,2'-bipyrrolidine derivatives as organocatalysts for the asymmetric michael addition of ketones and aldehydes to nitroolefins. Adv. Synth. Catal.2004,346,1147-1168
[100]Wang, W.; Wang, J.; Li, H. Direct, Highly enantioselective pyrrolidine sulfonamide catalyzed michael addition of aldehydes to nitrostyrenes. Angew. Chem.2005,117,1393; Angew. Chem. Int. Ed.2005,44,1369-1371
[2]尤天耙.手性化合物的现代研究方法.中国科学技术大学出版社,合肥,1993,pp 6-10
[3]张生勇,郭建全.不对称催化反应—原理及在有机合成中的应用,北京：科学出版社,2002
[4]周维善,庄治平,不对称反应,北京：科学出版社,1997
[5]殷元骐,蒋耀忠,不对称催化反应进展,北京：科学出版社,2000
[6]Dalko, P. L.; Moisan, L. Enantioselective organocatalysis. Angew. Chem. Int. Ed,2001,40, 3726-3748
[7]Dalko, P. L.; Moisan, L. In the golden age of organocatalysis. Angew. Chem., Int. Ed.2004, 43,5138-5175
[8]list, B. Proline-catalyzed asymmetric reactions. Tetrahedron.2002,58,5573-5590
[9]李经纬,徐利文,夏春谷.脯氨酸催化剂在不对称反应中的研究进展.有机化学.2004,24,23-28
[10]魏晓芳.光学活性脯氨酸催化的不对称有机合成反应.有机化学.2005,25,1619-1626
[11]Tang, Z.; Jiang, F.; Yu, L.-T.; Cui, X.; Gong, L.-Z.; Mi, A.-Q.; Jiang, Y.-Z.; Wu, Y.-D. Novel small organic molecules for a highly enantioselective direct aldol reaction. J. Am. Chem. Soc. 2003,125,5262-5263
[12]Tang, Z.; Yang, Z.-H.; Chen, X.-H.; Cun, L.-F.; Mi, A.-Q.; Jiang, Y.-Z.; Gong, L.-Z. A highly efficient organocatalyst for direct aldol reactions of ketones with aldedydes. J. Am. Chem. Soc.2005,127,9285-9289
[13]Tang, Z.; Jiang, F.; Cui, X.; Gong, L.-Z.; Mi, A.-Q.; Jiang, Y.-Z.; Wu, Y.-D. Enantioselective direct aldol reactions catalyzed by L-prolinamide derivatives. Proc. Natl. Acad. Sci. U.S.A. 2004,101,5755-5760
[14]Tang, Z.; Jiang, F.; Cui, X.; Gong, L.-Z.; Mi, A.-Q.; Jiang, Y.-Z.; Wu, Y.-D. Enantioselective direct aldol reactions catalyzed by L-prolinamide derivatives. PNAS, April 20,2004,101,16, 5755-5760
[15]Guo, H.-M.; Cun, L.-F.; Gong, L.-Z.; Mi, A.-Q.; Jiang, Y.-Z. Asymmetric direct aldol reaction catalyzed by an L-prolinamide derivative:Considerable improvement of the catalytic efficiency in the ionic liquid. Chem. Commun.2005,1450-1452
[16]Berkessel, A.; Koch, B.; Lex, J. Proline-derived N-sulfonylcarboxamides:Readily available, highly enantioselective and versatile catalysts for direct aldol reactions. Adv. Synth. Catal. 2004,346,1141-1146
[17]Cobb, A. J. A.; Shaw, D. M.; Longbottom. D. A.; Ley, S. V. Organocatalysis with proline derivatives:Improved catalysts for the asymmetric Mannich, nitro-Michael and aldol reactions. Org. Biomol. Chem.2005.3,84-96
[18]Yang, H.; Carter, R. G. N-(p-Dodecylphenylsulfonyl)-2-pyrrolidinecarboxamide:A practical proline mimetic for facilitating enantioselective aldol reactions. Org. Lett,2008,10, 4649-4652
[19]Zhang, S.-P.; Fu. X.-K.; Fu, S.-D.; Pan, J.-F. Highly efficient 4-phenoxy substituted organocatalysts derived from N-prolylsulfonamide for the asymmetric direct aldol reaction on water. Catalysis Communications.2009,10,401-405
[20]Fu, S.-D.; Fu, X.-K.; Zhang, S.-P.; Zou, X.-C.; Wu, X.-J.; Highly diastereo- and enantioselective direct aldol reactions by 4-tert-butyldimethylsiloxy-substituted organocatalysts derived from N-prolylsulfonamides in water. Tetrahedron:Asymmetry.2009, 20,2390-2396.
[21]Gryko, D.; Lipiriski, R. L-prolinethioamides-efficient organocatalysts for the direct asymmetric aldol reaction. Adv. Synth. Catal.2005,347,1948-1952
[22]Almasi, D.; Alonso, D. A.; Najeraa, C. Prolinamides versus prolinethioamides as recyclable catalysts in the enantioselective solvent-free inter-and intramolecular aldol reactions, Adv. Synth. Catal.2008,350,2467-2472
[23]Samanta, S.; Liu, J. Y.; Dodda, R.; Zhao C. G. C2-symmetric bisprolinamide as a highty efficient catalyst for direct aldol reaction. Org. Lett.2005,7,5321-5323.
[24]Chen, J.-R.; Lu, H.-H.; Li, X.-Y.; Cheng, L.; Wan, J.; Xiao, W.-J. Readily tunable and bifunctional l-prolinamide derivatives:design and application in the direct enantioselective aldol reactions. Org. Lett.2005,7,4543-4545
[25]Chen, J.-R.; Li, X.-Y,; Xing, X.-N.; Xiao, W.-J. Highly stereoselective palladium-catalyzed dithiocarbonylation of propargylic mesylates with thiols and carbon monoxide. J. Org. Chem. 2005,70,1802-1807
[26]Yang, Y.; He, Y.-H.; Guan, Z.; Huang, W.-D. A highly efficient large-scale asymmetric direct intermolecular aldol reaction employing L-prolinamide as a recoverable catalyst. Adv. Synth. Catal.2010,352,2579-2587
[27]Fu, Y.-Q.; Li, Z.-C.; Ding, L.-N.; Tao, J.-C.; Zhang, S.-H.; Tang, M.-S. Direct asymmetric aldol reaction catalyzed by simple prolinamide phenols. Tetrahedron:Asymmetry.2006,17, 3351-3357
[28]Chimni, S. S.; Mahajan, D. Small organic molecule catalyzed enantioselective direct aldol reaction in water. Tetrahedron:Asymmetry.2006,17,2108-2119
[29]He, L.; Tang, Z.; Cun, L.-F.; Mi, A.-Q.; Jiang, Y.-Z.; Gong, L.-Z. L-Proline amide-catalyzed direct asymmetric aldol reaction of aldehydes with chloroacetone. Tetrahedron.2006,62, 346-351
[30]Zhang, S.-P.; Fu, X.-K.; Fu, S.-D. Rationally designed 4-phenoxy substituted prolinamide phenols organocatalyst for the direct aldol reaction in water. Tetrahedron Letters 2009,50, 1173-1176
[31]Sato, K.; Kuriyama, M.; Shimazawa, R.; Morimoto, T.; Kakiuchi, K.; Shirai, R. Direct asymmetric aldol reactions catalyzed by L-proline-2,4,6-trinitroanilide. Tetrahedron Letters 2008,49,2402-2406
[32]Moorthy, J. N.; Saha, S. Highly diastereo- and enantioselective aldol Reactions in common organic solvents using N-arylprolinamides as organocatalysts with enhanced acidity. DOI:10.1002/ejoc.200800960
[33]Chen, J.-R.; An, X.-L.; Zhu, X.-Y.; Wang, X.-F.; Xiao, W.-J. Rational combination of two privileged chiral backbones:highly efficient organocatalysts for asymmetric direct aldol reactions between aromatic aldehydes and acylic ketones, J. Org. Chem.2008,73,6006-6009
[34]Agarwal, J.; Peddinti, R. K. Highly efficient and solvent-free direct aldol reaction catalyzed by glucosamine-derived prolinamide. Tetrahedron:Asymmetry.2010,21,1906-1909
[35]List, B.; Lerner, R. A.; Barbas, C F Ⅲ. Proline-catalyzed direct asymmetric aldol reactions. J. Am. Chem. Soc.2000,122,2395-23961
[36]List, B.; Pojarliev, P.; Martin, H. J. Efficient proline-catalyzed michael additions of unmodified ketones to nitro olefins. Org. Lett.2001,3,2423-24251
[37]Betancort, J. M.; Sakthivel, K. R.; Thayumanavan. Tetrahedron Lett.2001,42,4441-44441
[38]Mase, N.; Thayumanavan, R.; Tanaka, F. Direct asymmetric organocatalytic michael reactions of α,α-disubstituted aldehydes with β-nitrostyrenes for the synthesis of quaternary carbon-containing products. Org. Lett.2004,6,2527-2530
[39]Chi, Y.; Gellman, S. H. Diphenylprolinol methyl ether:A highly enantioselective catalyst for michael addition of aldehydes to simple enones. Org. Lett.2005,7,4253-4255
[40]Hayashi, Y.; Gotoh, H.; Hayashi, T.; Shoji, M. Angew. Chem. Int. Ed.2005,44,4212
[41]Zhu, S.-L.; Yu, S.-Y.; Ma, D. Highly efficient catalytic system for enantioselective michael addition of aldehydes to nitroalkenes in water. Angew. Chem. Int. Ed.2008,47,545-548
[42]Hayashi, Y.; Itoh, T.; Ohkubo, M.; Ishikawa, H. Asymmetric michael reaction of acetaldehyde catalyzed by diphenylprolinol silyl ether. Angew. Chem. Int. Ed.2008,47, 4722-4724
[43]Ren-Shi Luo, Jiang Weng, Hui-Bing Ai, Gui Lu, and Albert S. C. Chana, Highly efficient asymmetric michael reaction of aldehydes to nitroalkenes with diphenylperhydroindolinol silyl ethers as organocatalysts. Adv. Synth. Catal.2009,351,2449-2459
[44]Berkessel A, Groger H. Books on organocatalysis:Asymmetric organocatalysis:From biomimetic concepts to applications in asymmetric synthesis. Eds Wiley-VCH:Weinheim, 2005
[45]Dalko P. I. Enantioselective organocatalysis:Reactions and experimental procedures. Ed Wiley-VCH:Weinheim,2007
[46]Tian, S. K.; Chen, Y. G.; Hang, J. F.; Tang, L.; McDaid, P.; Deng, L. Asymmetric organic catalysis with modified cinchona alkaloids. Acc Chem Res,2004,37,621-631
[47]List, B. Introduction:Organocatalysis. Chem Rev,2007,107,5413-5415
[48]Enders, D.; Grondal, C.; Huttl, R. M. Asymmetric organocatalytic domino reactions. Angew Chem. Int. Ed.2007,46,1570-1581
[49]Dondoni, A.; Massi, A. Asymmetric organocatalysis:From infancy to adolescence. Angew Chem. Int. Ed.2008,47,4638-4660
[50]MacMillan, D. W. C. The advent and development of organocatalysis. Nature,2008,455, 304-308
[51]Movassaghi, M.; Jacobsen, E. N. The simplest enzyme. Science,2002,298,1904-1905
[52]Notz, W.; Tanaka, F.; Barbas, Ⅲ CF. Enamine-based organocatalysis with proline and diamines:The development of direct catalytic asymmetric aldol, mannich, michael, and diels-alder reactions. Acc. Chem. Res,2004,37,580-591
[53]Kazmaier, U. Amino acids—valuable organocatalysts in carbohydrate synthesis. Angew Chem. Int. Ed,2005,44,2186-2188
[54]Schetter, B.; Mahrwald, R. Modern aldol methods for the total synthesis of polyketides. Angew. Chem. Int. Ed.2006,45,7506-7525
[55]List, B. The ying and yang of asymmetric aminocatalysis. Chem. Commun,2006,8,819-824
[56]Geary, L. M.; Hultin, P. G. The state of the art in asymmetric induction:the aldol reaction as a case study. Tetrahedron:Asymmetry,2009,20,131-173
[57]Dalko, P. L.; Moisan, L. In the golden age of organocatalysis. Angew. Chem. Int. Ed.2004, 43,5138-5175
[58]Li, C.-J. Organic reactions in aqueous media with a focus on carbon-carbon bond formations: a decade update. Chem. Rev.2005,105,3095-3165
[59]Palomo, C.; Oiarbide, M.; Garca, J. M. Current progress in the asymmetric aldol addition reaction. Chem. Soc. Rev.2004,33,65-75
[60]Alcaide, B.; Almendros, P. The direct catalytic asymmetric cross-aldol reaction of aldehydes. Angew. Chem. Int. Ed,2003,42,858-860
[61]List, B.; Lerner, R. A.; Barbas. Ⅲ CF. Proline-catalyzed direct asymmetric aldol reaction (List and co-workers). J. Am. Chem. Soc.2000,122.2395-2396
[62]Notz, W.; List, B. Catalytic asymmetric synthesis of anti-1,2-diols. J. Am. Chem. Soc.2000, 122,7386-7387
[63]Bahmanyar, S.; Houk, K. N.; Martin, H. J.; List, B. Quantum mechanical predictions of the stereoselectivities of proline-catalyzed asymmetric intermolecular aldol reactions. J. Am. Chem. Soc.2003,125,2475-2479
[64]List, B.; Hoang, L.; Martin, H. J. New mechanistic studies on the proline-catalyzed aldol reaction. Proc. Natl. Acad. Sci. USA.2004,101,5839-5842
[65]Mukherjee, S.; Yang, J. W.; Hoffmann, S.; List, B. Asymmetric enamine catalysis. Chem. Rev.2007,107,5471-5569
[66]Chen, J.-R.; Liu, X.-P.; Zhu, X.-Y.; Li, L.; Qiao, Y.-F.; Zhang. J.-M.; Xiao, W.-J. Organocatalytic asymmetric aldol reaction of ketones with isatins:straightforward stereoselective synthesis of 3-alkyl-3-hydroxyindolin-2-ones. Tetrahedron,2007,63, 10437-10444
[67]Huang, W.-P.; Chen, J.-R.; Li, X.-Y.; Cao, Y.-J.; Xiao, W.-J. Asymmetric organocatalytic direct aldol reactions of cyclohexanone with aldehydes in brine. Can. J. Chem.2007,85, 208-213
[68]Guizzetti, S.; Benaglia, M.; Raimondi, L.; Celentano, G. Enantioselective direct aldol reaction "on water" promoted by chiral organic catalysts. Org. Lett.2007,9,1247-1250
[69]Guillena, G.; Najera, C.; Viozquez, S. F. N-Tosyl-(Sa)-binam-L-prolinamide as highly efficient bifunctional organocatalyst for the general enantioselective solvent-free aldol reaction. Synlett.2008,19,3031-3035
[70]Guillena, G.; Hita, M. D. C.; Najera, C.; Vioquez, S. F. A highly efficient solvent-free asymmetric direct aldol reaction organocatalyzed by recoverable (S)-binam-L-prolinamides. ESI-MS evidence of the enamine-iminium formation. J. Org. Chem.2008,73,5933-5943
[71]Wang, C.; Jiang, Y.; Zhang, X.-X.; Huang, Y.; Li, B.-G.; Zhang, G.-L. Rationally designed organocatalyst for direct asymmetric aldol reaction in the presence of water. Tetrahedron Lett. 2007,48,4281-4285
[72]Zhao, J.-P.; He, L.; Jiang, J.; Tang, Z.; Cun, L.-F.; Gong, L.-Z. Organo-catalyzed highly diastereo- and enantio-selective direct aldol reactions in water. Tetrahedron Lett.2008,49, 3372-3375
[73]Vishnumaya, M, R.; Singh, V. K. Highly efficient small organic molecules for enantioselective direct aldol reaction in organic and aqueous media. J. Org. Chem.2009,74, 4289-4297
[74]Chen, F.; Huang, S.; Zhang, H.; Liu, F.; Peng, Y. Proline-based dipeptides with two amide units as organocatalyst for the asymmetric aldol reaction of cyclohexanone with aldehydes. Tetrahedron.2008,64,9585-9591
[75]Moorthy, J. N.; Saha, S. Highly diastereo- and enantioselective aldol reactions in common organic solvents using N-arylprolinamides as organocatalysts with enhanced acidity. Eur. J. Org. Chem.2009,5,739-748
[76]Chimni. S. S.; Singh, S.; Mahajan, D. Protonated (S)-prolinamide derivatives—water compatible organocatalysts for direct asymmetric aldol reaction. Tetrahedron:Asymmetry. 2008,19,2276-2284
[77]Aratake, S.; Itoh, T.; Okano, T.; Nagae, N.; Sumiya, T.; Shoji, M.; Hayashi, Y. Highly diastereo- and enantioselective direct aldol reactions of aldehydes and ketones catalyzed by siloxyproline in the presence of water. Chem. Eur. J.2007,13,10246-10256
[78]Aratake, S.; Itoh, T.; Okano, T.; Usui, T.; Shoji, M.; Hayashi, Y. Small organic molecule in enantioselective, direct aldol reaction "in water". Chem. Commun.2007,24,2524-2526
[79]Hayashi, Y.; Aratake, S.; Itoh, T.; Okano, T.; Sumiya, T.; Shoji, M. Dry and wet prolines for asymmetric organic solvent-free aldehyde-aldehyde and aldehyde-ketone aldol reactions. Chem. Commun.2007,9,957-959
[80]Hayashi, Y.; Aratake, S.; Okano, T.; Takahashi, J.; Sumiya, T.; Shoji, M. Combined Proline-Surfactant Organocatalyst for the Highly Diastereo- and Enantioselective Aqueous Direct Cross-Aldol Reaction of Aldehydes. Angew. Chem. Int. Ed.2006,45,5527-5529
[81]Tang, Z.; Jiang, F.; Yu, L.-T.; Cui, X.; Gong, L.-Z.; Qiao, A.; Jiang, Y.-Z.; Wu, Y.-D. Novel Small Organic Molecules for a Highly Enantioselective Direct Aldol Reaction. J. Am. Chem. Soc.2003,125,5262-5263
[82]Tang, Z.; Jiang, F.; Yu, L.-T.; Cui, X.; Gong, L.-Z.; Mi, A.-Q.; Jiang, Y.-Z.; Wu, Y.-D. Proc. Natl. Acad. Sci. USA.2004,101,5775
[83]Tang, Z.; Yang, Z.-H.; Cun, L.-F.; Gong, L.-Z.; Mi, A.-Q.; Jiang, Y.-Z. Small peptides catalyze highly enantioselective direct aldol reactions of aldehydes with hydroxyacetone: Unprecedented regiocontrol in aqueous media. Org. Lett.2004,6,2285-2287
[84]Tang, Z.; Yang, Z.-H.; Chen, X.-H.; Cun, L.-F.; Mi, A.-Q.; Jiang, Y.-Z.; Gong, L.-Z. A highly efficient organocatalyst for direct aldol reactions of ketones with aldedydes. J. Am. Chem. Soc.2005,127,9285-9289
[85]He, L.; Tang, Z.; Cun. L.-F.; Mi, A.-Q.; Jiang, Y.-Z.; Gong, L.-Z. Tetrahedron.2005,62, 346
[86]Chen, J.-R.; Lu, H.-H.; Li, X.-Y.; Cheng, L.; Wan, J.; Xiao, W.-J. Readily Tunable and Bifunctional 1-Prolinamide Derivatives:Design and Application in the Direct Enantioselective Aldol Reactions. Org. Lett.2005,7,4543-4545
[87]Chen, J.-R.; Li, X.-Y.; Xing, X.-N.; Xiao, W.-J. Sterically and electronically tunable and bifunctional organocatalysts:Design and application in asymmetric aldol reaction of cyclic ketones with aldehydes. J. Org. Chem.2006,71,8198-8202
[88]Zhang, S. P.; Fu, X. K.; Fu, S. D.; Pan, J. F. Highly efficient 4-phenoxy substituted organocatalysts derived from N-prolylsulfonamide for the asymmetric direct aldol reaction on water. Cat. Commun,2009,10,401-405
[89]Zhang, S. P.; Fu, X. K.; Fu, S. D. Rationally designed 4-phenoxy substituted prolinamide phenols organocatalyst for the direct aldol reaction in water. Tetrahedron Lett.2009,50, 1173-1176
[90]Fu, S. D.; Fu, X. K.; Zhang, S. P.; Zou, X. C.; Wu, X. J. Highly diastereo- and enantioselective direct aldol reactions by 4-tert-butyldimethylsiloxy substituted organocatalysts derived from N-prolylsulfonamides in water. Tetrahedron:Asymmetry. 2009,20,2390-2396
[91]Wu, X. Y.; Jiang, Z. Q.; Shen, H. M.; Lu, Y. X. Highly efficient threonine-derived organocatalysts for direct asymmetric aldol reactions in water. Adv. Synth. Catal.2007,349, 812
[92]Qian, Y. B.; Zheng, X.; Wang, Y. M. A green and efficient asymmetric aldol reaction catalyzed by a chiral anion modified ionic liquid. Eur. J. Org. Chem.2010,3672-3677
[93]Mase, N.; Noshiro, N.; Mokuya, A.; Takabea, K. Adv. Effect of long chain fatty acids on organocatalytic aqueous direct aldol reactions. Synth. Catal.2009,351,2791-2796
[94]Rodriguez, B.; Bruckmann, A.; Bolm, C. A highly efficient asymmetric organocatalytic aldol reaction in a ball mill. Chem. Eur. J.2007,13,4710-4722
[95]Ramasastry, S. S. V.; Zhang, H.; Tanaka, F.; Barbas Ⅲ CF. Direct catalytic asymmetric synthesis of anti-1,2-Amino alcohols and syn-1,2-diols through organocatalytic anti-mannich and syn-aldol reactions. J. Am. Chem. Soc.2007,129,288-289
[96]Betancort, J. M.; Barbas, C. F. Ⅲ. Catalytic direct asymmetric michael reactions:Taming naked aldehyde donors. Org. Let.2001,3,3737-3740
[97]Alexakis, A.; Andrey, O. Diamine-catalyzed asymmetric michael additions of aldehydes and ketones to nitrostyrene. Org. Lett.2002,4,3611-3614
[98]Hayashi, Y.; Gotoh, H.; Hayashi, T.; Shoji, M. Diphenylprolinol silyl ethers as efficient organocatalysts for the asymmetric michael reaction of aldehydes and nitroalkenes. Angew. Chem. Int. Ed.2005,44,4212-4215
[99]Andrey, O.; Alexakis, A.; Tomassini, A.; Bernardinelli, G. The use of N-alkyl-2,2'-bipyrrolidine derivatives as organocatalysts for the asymmetric michael addition of ketones and aldehydes to nitroolefins. Adv. Synth. Catal.2004,346,1147-1168
[100]Wang, W.; Wang, J.; Li, H. Direct, Highly enantioselective pyrrolidine sulfonamide catalyzed michael addition of aldehydes to nitrostyrenes. Angew. Chem.2005,117,1393; Angew. Chem. Int. Ed.2005,44,1369-1371