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A combined DFT and NMR investigation of the zinc organometallic intermediate proposed in the syn-selective tandem chain extension-aldol reaction of ?-keto esters.

ABSTRACT: The tandem chain extension-aldol (TCA) reaction of ?-keto esters provides an ?-substituted ?-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 ?-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.

SUBMITTER: Aiken KS

PROVIDER: S-EPMC3401335 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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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.

Aiken Karelle S KS Eger Wilhelm A WA Williams Craig M CM Spencer Carley M CM Zercher Charles K CK

The Journal of organic chemistry 20120703 14

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 T ...[more]

PMID: 22703563

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