Bronsted acids as additives for the direct asymmetric aldol reaction catalyzed by L-prolinethioamides. Direct evidence for enamine - Iminium catalysis
Bronsted acids as additives for the direct asymmetric aldol reaction catalyzed by L-prolinethioamides. Direct evidence for enamine - Iminium catalysis
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DOI：
10.1021/jo062149k
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发表时间：
2007-02-02
影响因子：
3.6
通讯作者：
Lipinski, Radoslaw
中科院分区：
文献类型：
--
作者：
Gryko, Dorota;Zimnicka, Magdalena;Lipinski, Radoslaw
用质子化的L-丙硫酰胺代替游离碱的衍生物1作为有机催化剂，对羟醛直接加成反应的产率和立体化学过程都有深远的影响。4-硝基苯甲醛(2)在质子化催化剂1中心点TFA的催化下与丙酮反应，得到羟醛产品3，产率达99%，ee达98%。催化剂负载量可降至2.5mol%。考察了20多种不同的酸作为助剂的作用，并讨论了它们作为助催化剂的作用。此外，用电喷雾质谱和氢核磁共振技术研究了L-丙氨硫胺盐与丙酮的反应，揭示了直接羟醛缩合反应的机理。已经明确地证实了推测的亚胺盐10的形成。
The use of protonated L-prolinethioamide instead of the free base derivative 1 as the organocatalyst for the direct aldol addition has a profound and appreciable effect on both the yield and the stereochemical course of the reaction. 4-Nitrobenzaldehyde (2) reacts with acetone in the presence of the protonated catalyst 1 center dot TFA, affording aldol product 3 with a yield up to 99% and an ee up to 98%. The catalyst loading can be lowered to 2.5 mol %. More than 20 different acids were investigated as an additive, and its role as cocatalyst has been discussed. Furthermore, reactions of L-prolinethioamide salts with acetone have been monitored using ESI-MS and H-1 NMR techniques, giving insight into the mechanism of the direct aldol reaction. The presumed formation of the iminium salt 10 has been unambiguously confirmed.