A Combined DFT and NMR Investigation of the Zinc Organometallic Intermediate Proposed in the Syn-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.

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Journal of Organic Chemistry


American Chemical Society

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