Clemente Fernando R, Houk K N
Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095-1569, USA.
J Am Chem Soc. 2005 Aug 17;127(32):11294-302. doi: 10.1021/ja0507620.
The effects of different amino acid catalysts and substrate substituents on the stereoselectivity of the title reactions have been studied with the aid of density functional theory methods. Experimental data available in the literature have been compiled. B3LYP/6-31G(d) calculations match the general experimental trends and provide useful insights into the origins of the variations in stereoselectivities. Acyclic primary amino acids allow a greater conformational flexibility in the aldol transition states compared with proline. This makes them poorer enantioselective catalysts with triketone substrates with a methyl ketone side chain. The steric repulsion upon substitution at the terminal methyl group increases the energy difference between anti- and syn-chairs with primary amino acid catalysts and, consequently, the stereoselectivities. Proline, in contrast, is a poor catalyst for the latter reactions because the substituent's steric bulkiness raises the activation energy of the favored C-C bond-forming pathway.
借助密度泛函理论方法，研究了不同氨基酸催化剂和底物取代基对标题反应立体选择性的影响。已汇编了文献中可用的实验数据。B3LYP/6-31G(d)计算结果与一般实验趋势相符，并为立体选择性变化的起源提供了有用的见解。与脯氨酸相比，无环伯氨基酸在醛醇过渡态中具有更大的构象灵活性。这使得它们作为具有甲基酮侧链的三酮底物的对映选择性催化剂较差。在伯氨基酸催化剂作用下，末端甲基取代时的空间排斥增加了反式椅式和顺式椅式之间的能量差，从而提高了立体选择性。相比之下，脯氨酸是后一类反应的不良催化剂，因为取代基的空间位阻增加了有利的碳-碳键形成途径的活化能。
