Palladium-catalyzed asymmetric alkylation in the synthesis of cyclopentanoid and cycloheptanoid core structures bearing all-carbon quaternary stereocenters

General catalytic asymmetric routes toward cyclopentanoid and cycloheptanoid core structures embedded in numerous natural products have been developed. The central stereoselective transformation in our divergent strategies is the enantioselective decarboxylative alkylation of seven-membered beta-ketoesters to form alpha-quaternary vinylogous esters. Recognition of the unusual reactivity of beta-hydroxyketones resulting from the addition of hydride or organometallic reagents enabled divergent access to gamma-quaternary acylcyclopentenes through a ring contraction pathway or gamma-quaternary cycloheptenones through a carbonyl transposition pathway. Synthetic applications of these compounds were explored through the preparation of mono-, bi-, and tricyclic derivatives that can serve as valuable intermediates for the total synthesis of complex natural products. This work complements our previous work with cyclohexanoid systems. (C) 2011 Elsevier Ltd. All rights reserved.