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

Author:
Klosowski, Daniel W., Hethcox, J. Caleb, Paull, Daniel H., Fang, Chao, Donald, James R., Shugrue, Christopher R., Pansick, Andrew D., Martin, Stephen F.
Source:
Journal of organic chemistry 2018 v.83 no.11 pp. 5954-5968
ISSN:
1520-6904
Subject:
carboxylic acids, catalysts, chemical structure, diastereoselectivity, enantioselective synthesis, enantioselectivity, epoxidation reactions, lactones, organic chemistry, protocols, regioselectivity
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.
Agid:
6047208