Selective γ Alkylation of Dienolate Anions Derived from α,β-Unsaturated Acids. Applications to the Synthesis of Isoprenoid Olefins

John A. Katzenellenbogen, Ann L. Crumrine

Research output: Contribution to journalArticlepeer-review

Abstract

Lithium dienolates derived from α,β-unsaturated carbonyl compounds generally undergo alkylation reactions nearly exclusively at the α (rather than the γ) carbon. Changing the counterion from lithium to copper(I), however, has a remarkable effect on the alkylation regioselectivity of these dienolates. A systematic investigation has been made of the reaction of dienolates derived from (Z)-and (£)-3-methyl-2-hexenoic (2a and 3a) and crotonic (4a), senecioic (5a), tiglic (6a), and angelic (7a) acids with a variety of allylic electrophiles. The lithium dianions all undergo exclusive a alkylation, but the dicopper dianions undergo γ-selective alkyation (62-99%). (Lower γ selectivities were found in a previous study of the corresponding esters. 16) The γ-substituted products of the acids 4a, 6a, and 7a were exclusively of the £ geometry, while 50% and 81% Z isomers were found with the acids 5a and 2a, respectively. Allylic electrophiles that are unsubstituted at the γ carbon react with the copper dienolates mainly in an Sn2′ fashion, giving products in which the allylic portion has been transposed. Those electrophiles that are disubstituted react exclusively by direct (Sn2) displacement, but those with only one substituent undergo a mixture of Sn2 and Sn2′ attack. The γ-selective alkylation of copper dienolates can be used as a convenient prenologation process in natural product synthesis. Farnesoic acid has been synthesized from geranyl bromide, and dl-lanceol, from an allylic bromide derived from limonene.

Original languageEnglish (US)
Pages (from-to)4925-4935
Number of pages11
JournalJournal of the American Chemical Society
Volume98
Issue number16
DOIs
StatePublished - Aug 1 1976

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry
  • Biochemistry
  • Colloid and Surface Chemistry

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