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Synthesis of Substituted Chromanones: An Organocatalytic Aldol/oxa-Michael Reaction

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journal contribution
posted on 06.08.2010, 00:00 by Jeffrey D. Butler, Wayne E. Conrad, Michael W. Lodewyk, James C. Fettinger, Dean J. Tantillo, Mark J. Kurth
A diastereoselective organocatalytic aldol/oxa-Michael reaction has been developed to efficiently deliver medicinally relevant 2,3-ring-substituted chromanones. Development of this synthetic strategy revealed an unexpected kinetic anti-Saytzeff elimination; an origin for the observed selectivity is suggested on the basis of the results of quantum chemical calculations. This unusual kinetic selectivity necessitated an isomerization protocol that in turn led to the discovery of an intriguing Pd-mediated isomerization/intramolecular Friedel−Crafts-type alkylation.