Borane-Mediated Aldol Cycloreduction of Monoenone Monoketones: Diastereoselective Formation of Quaternary Centers
Ryan R. Huddleston, David F. Cauble and Michael J. Krische*
*Department of Chemistry and Biochemistry, University of Texas at Austin,
Austin, Texas 78712, Email: mkrische
mail.utexas.edu
R. R. Huddleston, D. F. Cauble, M. J. Krische, J. Org. Chem., 2003, 68, 11-14.
DOI: 10.1021/jo020629f
Abstract
A tandem 1,4-reduction-aldol cyclization is induced by exposure of monoenone monoketones to catecholborane in THF at ambient temperature. Six-membered cyclic aldol products are formed in excellent yield with high levels of syn diastereoselectivity for aromatic and heteroaromatic enones. Five-membered ring formation proceeds less readily, but the yield is improved through addition of Rh(I) salts.
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stereochemical model accounting for the syn diastereoselectivity
Details
The document discusses the borane-mediated aldol cycloreduction of monoenone monoketones, focusing on the diastereoselective formation of quaternary centers. The study, conducted by Ryan R. Huddleston, David F. Cauble, and Michael J. Krische at the University of Texas at Austin, reveals that exposing monoenone monoketones to catecholborane in THF at ambient temperature results in tandem 1,4-reduction-aldol cyclization. This process yields six-membered cyclic aldol products with high syn diastereoselectivity for aromatic and heteroaromatic enones. However, five-membered ring formation is less efficient, though the yield improves with the introduction of Rh(I) salts. The research builds on previous methods of catalytic reductive condensation and explores the utility of boron enolates in aldol chemistry. The study also highlights the challenges of competitive carbonyl reduction and the need for selective borane reagents. The findings suggest that aldol cyclizations involving (Z)-boron enolates are more challenging for five-membered rings than six-membered rings. Future research aims to develop broader substrate scope, enantioselective catalytic systems, and related catalytic functional group interconversions. The work is supported by various foundations and grants, and detailed experimental procedures and spectral data are provided.
Diastereoselective Cobalt-Catalyzed Aldol and Michael Cycloreductions
T.-G. Baik, A. L. Luis, L.-C. Wang, M. J. Krische, J. Am. Chem. Soc., 2001, 123, 5112-5113.
Key Words
β-hydroxy ketones, cyclohexanols, catecholborane
ID: J42-Y2003-210
