Isenegger Patrick G, Pfaltz Andreas
Department of Chemistry, University of Basel, St. Johanns-Ring 19, 4056, Basel, Switzerland.
Chem Rec. 2016 Dec;16(6):2534-2543. doi: 10.1002/tcr.201600072. Epub 2016 Jul 15.
In this account, we discuss a mass spectrometric method that enables unambiguous identification of intermediates involved in the enantioselective step of a catalytic cycle. This method, which we originally developed for rapid evaluation of chiral catalysts, is based on monitoring the back reaction of mass-labeled quasi-enantiomeric products by ESI-MS. In this way, the intrinsic enantioselectivity of a chiral catalyst can be determined directly by quantification of catalytically relevant intermediates. By comparing the results from the forward and back reaction, direct evidence for the involvement of a catalytic intermediate in the enantioselective step can be obtained. In addition, insights about the energy profile of the catalytic cycle may be gained. The potential of back reaction screening as a mechanistic tool is demonstrated for organocatalytic aldol reactions, 1,4-additions of aldehydes to nitroolefins, Diels-Alder reactions, Michael additions, and Morita-Baylis-Hillman reactions.
在本报告中，我们讨论了一种质谱方法，该方法能够明确鉴定催化循环对映选择性步骤中涉及的中间体。我们最初开发此方法用于快速评估手性催化剂，它基于通过电喷雾电离质谱（ESI-MS）监测质量标记的准对映体产物的逆反应。通过这种方式，手性催化剂的固有对映选择性可直接通过对催化相关中间体的定量来确定。通过比较正向和逆向反应的结果，可以获得催化中间体参与对映选择性步骤的直接证据。此外，还可以深入了解催化循环的能量分布情况。逆反应筛选作为一种机理工具的潜力在有机催化的羟醛缩合反应、醛与硝基烯烃的1,4-加成反应、狄尔斯-阿尔德反应、迈克尔加成反应以及森田-贝利斯-希尔曼反应中得到了证明。
