Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA.
J Am Chem Soc. 2012 Apr 18;134(15):6741-50. doi: 10.1021/ja300415t. Epub 2012 Apr 9.
Detailed mechanistic study of two reactions catalyzed by diarylprolinol ether catalysts, the conjugate addition of aldehydes to nitro-olefins and the α-chlorination of aldehydes, leads to the proposal that the stereochemical outcome in these cases is not determined by the transition state of the step in which the stereogenic center is formed from enamine attack on the electrophile but instead is correlated with the relative stability and reactivity of diastereomeric intermediates downstream in the catalytic cycle. This combination of kinetic and thermodynamic factors illustrates a remarkable Curtin-Hammett scenario that can result in either an enhancement or an erosion of the selectivity that would be predicted by the transition state for enamine attack on the electrophile. Evidence is offered to suggest that this concept may represent a general phenomenon for pyrrolidine-based catalysts lacking an acidic directing proton. Implications for catalyst and reaction design are discussed.
详细的机制研究表明，二芳基脯氨醇醚催化剂可以催化两种反应，即醛与硝基烯烃的共轭加成反应和醛的α-氯代反应。研究提出，在这些情况下，立体化学产物的结果不是由手性中心从烯胺攻击亲电试剂形成的过渡态决定的，而是与催化循环中后续的非对映中间体的相对稳定性和反应性相关。这种动力学和热力学因素的结合说明了一个显著的 Curtin-Hammett 情景，它可以导致亲电试剂的烯胺攻击过渡态预测的选择性增强或侵蚀。有证据表明，对于缺乏酸性导向质子的吡咯烷类催化剂，这一概念可能代表一种普遍现象。讨论了对催化剂和反应设计的影响。
