Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore.
Org Biomol Chem. 2012 Apr 28;10(16):3229-35. doi: 10.1039/c2ob06993h. Epub 2012 Mar 9.
(S)-Proline-catalyzed nitro-Michael additions of aldehydes and ketones to β-nitrostyrene were investigated computationally (MP2/6-311+G**//M06-2X/6-31G**). Contrary to what is usually assumed in organocatalysis, the lowest-energy transition states of proline-catalyzed nitro-Michael reactions do not necessarily involve the carboxylic acid group of the proline moiety directing the incoming nitroalkene to the same face through hydrogen bonding. For the aldehyde substrates examined, the TS leading to the major (R,S) product was found to involve the anti-enamine and nitroalkene approaching from the opposite face of the carboxyl group. In the case of ketone substrates, the lowest-energy TSs leading to both enantiomeric products are characterized by the absence of hydrogen bonds and s-cis conformation of the carboxyl group, which functions as an electron donor to stablize the developing iminium. When both hydrogen bonded and non-hydrogen bonded types of TSs are considered, the calculated enantioselectivities for Michael additions of aldehyde and ketone substrates are in good agreement with experimental findings.
（S）-脯氨酸催化的醛和酮与β-硝基苯乙烯的硝迈克尔加成反应进行了计算研究（MP2/6-311+G**//M06-2X/6-31G**）。与通常在有机催化中假设的情况相反，脯氨酸催化的硝迈克尔反应的最低能量过渡态不一定涉及脯氨酸部分的羧酸基团通过氢键将进入的硝基烯烃引导到相同的面。对于所研究的醛底物，发现导致主要（R，S）产物的 TS 涉及反烯胺和硝基烯烃从羧基的相反面接近。对于酮底物，导致两种对映体产物的最低能量 TS 都以不存在氢键和羧基的 s-cis 构象为特征，该构象作为电子供体稳定形成的亚胺。当同时考虑氢键和非氢键类型的 TS 时，计算出的醛和酮底物的迈克尔加成的对映选择性与实验结果吻合良好。
