Amino acid catalyzed direct asymmetric aldol reactions: A bioorganic approach to catalytic asymmetric carbon-carbon bond-forming reactions
Amino acid catalyzed direct asymmetric aldol reactions: A bioorganic approach to catalytic asymmetric carbon-carbon bond-forming reactions
复制标题
DOI：
10.1021/ja010037z
复制
发表时间：
2001-06-06
影响因子：
15
通讯作者：
Barbas, CF
中科院分区：
文献类型：
--
作者：
Sakthivel, K;Notz, W;Barbas, CF
直接不对称催化羟醛缩合反应已成功地进行使用醛和未改性的酮与市售的手性环仲胺一起作为催化剂。基于结构的催化剂筛选确定了L-脯氨酸和5，5-二甲基噻唑烷-4-羧酸盐（DMTC）作为最强的氨基酸催化剂用于无环和环状酮作为羟醛供体与芳香族和脂肪族醛的反应，以提供具有高区域选择性、非对映选择性和对映选择性的相应羟醛产物。使用羟基丙酮作为羟醛供体的反应提供作为主要产物的反式-1，2-二醇，ee值高达> 99%。假设反应通过无金属的Zimmerman-Traxler型过渡态进行，并涉及烯胺中间体。所观察到的产物的立体化学与所提出的过渡态一致。非线性效应的缺乏提供了进一步的支持证据。该反应耐受少量的水（
Direct asymmetric catalytic aldol reactions have been successfully performed using aldehydes and unmodified ketones together with commercially available chiral cyclic secondary amines as catalysts. Structure-based catalyst screening identified L-proline and 5,5-dimethyl thiazolidinium-4-carboxylate (DMTC) as the most powerful amino acid catalysts for the reaction of both acyclic and cyclic ketones as aldol donors with aromatic and aliphatic aldehydes to afford the corresponding aldol products with high regio-, diastereo-, and enantioselectivities. Reactions employing hydroxyacetone as an aldol donor provide anti-1,2-diols as the major product with ee values up to > 99%. The reactions are assumed to proceed via a metal-free Zimmerman-Traxler-type transition state and involve an enamine intermediate. The observed stereochemistry of the products is in accordance with the proposed transition state. Further supporting evidence is provided by the lack of nonlinear effects. The reactions tolerate a small amount of water (