The absolute control of stereochemistry is frequently essential in the synthesis of important pharmaceuticals, food additives and pheromones. Despite the impressive progress that has been achieved over the past decade, numerous challenges and opportunities remain. In many areas, there is a need for improvements in economy, chemoselectivity and scope. Of special interest are new methods to achieve multiple stereocontrol and enantioselective modifications of the many useful organotransition metal reactions not yet suitably exploited. Proposed herein is a powerful new approach to organic stereocontrol, based on the use of 2-alkenyl-1,3-dioxolan-4-ones, that has the potential to rival and complement the success of the Sharpless epoxidation as a stereocontrolled source of 3-carbon synthons. A series of interrelated methodologies are proposed, including 1) new, direct and Pd-catalyzed conjugate addition reactions, 2) new, allylnickel homoenolate equivalent reactions and 3) new enol equivalent reactions. The products of the stereocontrolled conjugate addition and homoenolate methodologies are the starting materials for the enantioselective enol functionalization methodology. The latter in turn provides materials suitable for further stereocontrolled elaborations via extentions of known diastereoselective dioxolanone ring-opening reactions. The integration of these methodologies to achieve multiple stereocontrol and annulative syntheses is proposed. Fundamentally interesting issues of organometallic conformational equilibria and reaction stereochemistry are also addressed and are expected to provide insights of predictive utility both in this work and in the future development of organometallic methodologies. The initial targets of the proposed methodologies include intermediates involved in the synthesis of monoterpene alkaloids, iridoids, insect pheromones, alpha-amino acids, macrolide antibiotics and enkephalinase inhibitors.
