Selectivity Guidelines and a Reductive Elimination-Based Model for Predicting the Stereochemical Course of Conjugate Addition Reactions of Organocuprates to γ-Alkoxy-α,β-enoates

• Published in: Journal of organic chemistry 2006-03, Vol.71 (7), p.2630-2640
• Main Authors: Kireev, Artem S, Manpadi, Madhuri, Kornienko, Alexander
• Format: Article
• Language: English
• Subjects: Alkenes - chemistry; Chemistry; Copper - chemistry; Esters - chemical synthesis; Esters - chemistry; Exact sciences and technology; Kinetics and mechanisms; Molecular Conformation; Organic chemistry; Organometallic Compounds - chemistry; Oxidation-Reduction; Reactivity and mechanisms; Stereoisomerism
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo052383v

Current models used to predict the stereochemical outcome of organocopper conjugate addition processes focus on the nucleophilic addition step as stereochemistry-determining. Recent kinetic, NMR, kinetic isotope effect, and theoretical density functional studies strongly support the proposal that stereochemical preferences in these processes are dictated by the reductive elimination step, transforming CuIII to CuI intermediates. A new model that considers various steric and stereoelectronic factors involved in the transition state of the reductive elimination step is proposed and then used to interpret the results of systematic studies of arylcuprate conjugate addition reactions with cis and trans γ-alkoxy-α,β-enoates. The results give rise to the following selectivity guidelines for this process. To achieve high anti-addition diastereoselectivities the use of trans esters with a bulky nonalkoxy substituent at the γ-position is recommended. While stereoelectronics disfavor syn-addition, a judicious choice of properly sized γ-substituents may lead to the predominant formation of syn-products, especially with cis enoates. However, high syn-selelectivities may be achieved by using γ-amino-α,β-enoates.