Institut für Organische Chemie, Universitätsstrasse 31, 93053 Regensburg Universität, Regensburg, Germany.
Chemistry. 2012 Mar 12;18(11):3362-70. doi: 10.1002/chem.201102660. Epub 2012 Feb 10.
As part of our ongoing studies to provide an experimental basis for the improved understanding of organocatalytic reaction mechanisms we present a study on the influence of amine bases on enamine intermediate stabilization in proline catalysis. The (partial) deprotonation of the proline acid function is displayed by characteristic shifts of certain proton resonances and is also manifested by an increase of the amount of enamine intermediate upon reaching a critical pK(aH). Strong bases, such as 1,8-diazabicyclo[5.4.0]-undec-7-ene (DBU), allow for outstanding enamine stabilization in various solvents and, hence, permit the detection of enamine species that have been inaccessible until now (illustrated by the observation of minor amounts of Z enamines). The in situ NMR detection of a prolinate-DBUH(+) ion pair supports the well-documented reversal of enantioselectivity of proline-catalyzed aminations in the presence of amine bases by disabling the bifunctional activity and switching to a "simple" stereocontrol effect (as known from the Jørgensen/Hayashi-type diarylprolinol ethers). In addition, the possibility of attractive ionic interactions between both the iminium ion and prolinate enamines available in the presence of strong amine bases suggests promotion of the Mannich pathway in aldol reactions to mainly form condensation products.
作为我们正在进行的研究的一部分，旨在为深入理解有机催化反应机制提供实验基础，我们研究了胺碱对脯氨酸催化中烯胺中间物稳定化的影响。脯氨酸酸功能的（部分）去质子化通过某些质子共振的特征位移显示出来，并且当达到临界 pK(aH) 时，烯胺中间物的量也会增加。强碱，如 1,8-二氮杂二环[5.4.0]-十一-7-烯（DBU），允许在各种溶剂中出色地稳定烯胺，因此可以检测到迄今为止无法检测到的烯胺物种（通过观察少量 Z 烯胺来说明）。脯氨酸-DBUH(+)离子对的原位 NMR 检测支持了在胺碱存在下脯氨酸催化的胺化反应对映选择性反转的良好记录，通过禁用双功能活性并切换到“简单”立体控制效应（如已知的 Jørgensen/Hayashi 型二芳基脯氨醇醚）。此外，在存在强胺碱的情况下，亚氨基离子和脯氨酸烯胺之间可能存在有吸引力的离子相互作用，这表明促进了曼尼希途径在醛醇反应中主要形成缩合产物。
