A Combined DFT and NMR Investigation of the Zinc Organometallic Intermediate Proposed in the <i>Syn</i>-Selective Tandem Chain Extension–Aldol Reaction of β-Keto Esters

The tandem chain extension–aldol (TCA) reaction of β-keto esters provides an α-substituted γ-keto ester with an average syn:anti selectivity of 10:1. It is proposed that the reaction proceeds via a carbon–zinc bound organometallic intermediate potentially bearing mechanistic similarity to the Reformatsky reaction. Evidence, derived from control Reformatsky reactions and a study of the structure of the TCA intermediate utilizing DFT methods and NMR spectroscopy, suggests the γ-keto group of the TCA intermediate plays a significant role in diastereoselectivity observed in this reaction. Such coordination effects have design implications for future zinc mediated reactions.β-酮酸酯的串联链延伸-羟醛（Tandem Chain Extension–Aldol, TCA）反应可生成α-取代的γ-酮酸酯，其平均顺式:反式非对映选择性比例为10:1。研究表明，该反应经由碳锌键合的有机金属中间体进行，其反应机理与雷福尔马茨基反应（Reformatsky reaction）存在潜在相似性。通过对照雷福尔马茨基反应，以及利用密度泛函理论（Density Functional Theory, DFT）方法与核磁共振波谱法对TCA中间体结构展开的研究，所得证据表明，TCA中间体的γ-酮基团对本反应中观测到的非对映选择性具有显著影响。这类配位效应对未来锌介导反应的设计具有指导意义。