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

Karelle S. Aiken; Wilhelm A. Eger; Craig M. Williams; Carley M. Spencer; Charles K. Zercher

doi:10.1021/jo3004925

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

Karelle S. Aiken, Wilhelm A. Eger, Craig M. Williams, Carley M. Spencer, Charles K. Zercher

Biochemistry, Chemistry, & Physics

Research output: Contribution to journal › Article › peer-review

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Abstract

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.

Original language	English
Pages (from-to)	5942-5955
Number of pages	14
Journal	Journal of Organic Chemistry
Volume	77
Issue number	14
DOIs	https://doi.org/10.1021/jo3004925
State	Published - Jul 20 2012

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title = "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",

abstract = "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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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.; Eger, Wilhelm A.; Williams, Craig M. et al.
In: Journal of Organic Chemistry, Vol. 77, No. 14, 20.07.2012, p. 5942-5955.

Research output: Contribution to journal › Article › peer-review

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T1 - 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

AU - Aiken, Karelle S.

AU - Eger, Wilhelm A.

AU - Williams, Craig M.

AU - Spencer, Carley M.

AU - Zercher, Charles K.

PY - 2012/7/20

Y1 - 2012/7/20

N2 - 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.

AB - 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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JO - Journal of Organic Chemistry

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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

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