Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, USA.
J Am Chem Soc. 2012 Sep 12;134(36):14973-81. doi: 10.1021/ja3052975. Epub 2012 Aug 31.
The basis for diastereoselectivity in Lewis-acid-catalyzed Mukaiyama aldol reactions was studied using density functional theory. By exploring the conformations of the transition structures for the diastereodifferentiating step of seven different reactions, simple models were generated. The effects of varying the substituents on the enol carbon and the α-carbon of the silyl enol ether from methyl to tert-butyl groups and the substituent on the aldehyde from methyl to phenyl groups were investigated by comparison of the transition structures for different reactions. Expanding on the previous qualitative models by Heathcock and Denmark, we found that while the pro-anti pathways take place via antiperiplanar transition structures, the pro-syn pathways prefer synclinal transition structures. The relative steric effects of the Lewis acid and trimethyl silyl groups and the influence of E/Z isomerism on the aldol transition state were investigated. By calculating 36 transition structures at the M06/6-311G*//B3LYP/6-31G* level of theory and employing the IEFPCM polarizable continuum model for solvation effects, this study expands the mechanistic knowledge and provides a model for understanding the diastereoselectivity in Lewis-acid-catalyzed Mukaiyama aldol reactions.
利用密度泛函理论研究了路易斯酸催化的 Mukaiyama 羟醛反应的非对映选择性的基础。通过探索七种不同反应的非对映选择性区分步骤的过渡态构象，生成了简单的模型。通过比较不同反应的过渡态，研究了烯醇碳和硅基烯醇醚的α-碳上取代基从甲基到叔丁基基团以及醛上取代基从甲基到苯基基团的变化对反应的影响。在 Heathcock 和 Denmark 的先前定性模型的基础上进行扩展，我们发现尽管 pro-anti 途径通过反式平面过渡态发生，但 pro-syn 途径更倾向于顺式过渡态。研究了路易斯酸和三甲基硅基的相对空间效应以及 E/Z 异构体对羟醛过渡态的影响。通过在 M06/6-311G*//B3LYP/6-31G*理论水平上计算 36 个过渡态，并采用 IEFPCM 极化连续模型进行溶剂化效应的计算，本研究扩展了反应机制的知识，并提供了理解路易斯酸催化的 Mukaiyama 羟醛反应的非对映选择性的模型。
