Selective γ Alkylation of Copper Enolates Derived from α, β-Unsaturated Acids: Factors Affecting Scope and Regio- and Stereoselectivity

Patricia M. Savu, John A. Katzenellenbogen

Research output: Contribution to journalArticlepeer-review

Abstract

Copper dienolates derived from α, β-unsaturated acids undergo alkylation at the γ-carbon with high regioselectivity. A systematic investigation has been made of several factors that affect the γ-alkylation process of the dienolate derived tiglic acid (1): alterations in the nature of the counterion, in the stoichiometry of cuprous ion, and in the nature of the electrophile. Compared to allylic electrophiles, nonallylic electrophiles react with copper dienolates sluggishly and with little selectivity for the γ-carbon; vinylic epoxides, however, are particularly good alkylating agents. They undergo allylic transposition and react at the γ-carbon of the dienolate with high selectivity (70-90%), generating an allylic unit that forms part of a 1, 5-diene skeleton oxygenated at both ends. Tiglic (1) and crotonic (3) acids react with vinylic epoxides to form a 1, 5-diene with entirely E stereochemistry at the 2, 3 double bond, while senecioic acid (2) forms a 1, 5-diene with mostly Z stereochemistry at the 2, 3 double bond. Geometry at the 6, 7 double bond depends both on the, β-unsaturated acid used and on the structure of the epoxide. With allylic electrophiles under direct (SN2) attack, stereochemical analysis showed that some isomerization occurs around the 6, 7 double bond (derived from the electrophile). Addition of cuprous ion to the lithium dianion of 2-hexenoic acid (17) was found to enhance the regioselectivity of γ alkylation, but a subsequent Michael addition reaction limits the potential of γ alkylation in this system.

Original languageEnglish (US)
Pages (from-to)239-250
Number of pages12
JournalJournal of Organic Chemistry
Volume46
Issue number2
DOIs
StatePublished - Jan 1981

ASJC Scopus subject areas

  • Organic Chemistry

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