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.
Department
Chemistry
Publication Date
7-1-2012
Journal Title
Journal of Organic Chemistry
Publisher
American Chemical Society
Digital Object Identifier (DOI)
10.1021/jo3004925
Document Type
Article
Recommended Citation
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, K. A.; Eger, W. A.; Williams, C. M.; Spencer, C. M.; Zercher, C. K. J. Org. Chem. 2012, 77, 5942-5955.
Rights
Copyright © 2012, American Chemical Society