Enantioselective Halolactonization Reactions using BINOL-Derived Bifunctional Catalysts: Methodology, Diversification, and Applications

Daniel W. Klosowski, J. Caleb Hethcox, Daniel H. Paull, Chao Fang, James R. Donald, Christopher R. Shugrue, Andrew D. Pansick, Stephen F. Martin

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

A general protocol is described for inducing enantioselective halolactonizations of unsaturated carboxylic acids using novel bifunctional organic catalysts derived from a chiral binaphthalene scaffold. Bromo- and iodolactonization reactions of diversely substituted, unsaturated carboxylic acids proceed with high degrees of enantioselectivity, regioselectivity, and diastereoselectivity. Notably, these BINOL-derived catalysts are the first to induce the bromo- and iodolactonizations of 5-alkyl-4(Z)-olefinic acids via 5-exo mode cyclizations to give lactones in which new carbon-halogen bonds are created at a stereogenic center with high diastereo- and enantioselectivities. Iodolactonizations of 6-substituted-5(Z)-olefinic acids also occur via 6-exo cyclizations to provide δ-lactones with excellent enantioselectivities. Several notable applications of this halolactonization methodology were developed for desymmetrization, kinetic resolution, and epoxidation of Z-alkenes. The utility of these reactions is demonstrated by their application to a synthesis of precursors of the F-ring subunit of kibdelone C and to the shortest catalytic, enantioselective synthesis of (+)-disparlure reported to date.

Original languageEnglish (US)
Pages (from-to)5954-5968
Number of pages15
JournalJournal of Organic Chemistry
Volume83
Issue number11
DOIs
StatePublished - Jun 1 2018
Externally publishedYes

ASJC Scopus subject areas

  • Organic Chemistry

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