Organocatalyzed, enantioselective synthesis of bicyclo-[2.2.2]-octanes containing benzylic, all-carbon quaternary centers

Proline aryl sulfonamide-catalyzed, multi-component couplings have been developed for accessing densely functionalized [2.2.2] bicyclic ketones containing up to four contiguous chiral centers including an all-carbon benzylic quaternary center in high enantio- and diastereoselectivity. Application to the bicyclic core of the recently isolated alkaloid kopsonoline is illustrated. (C) 2010 Elsevier Ltd. All rights reserved.