Mark Biscoe

Rethinking asymmetric synthesis: The development of general metal-catalyzed cross-coupling reactions that enable the use of optically active nucleophiles

The development of transition metal-catalyzed cross-coupling reactions has greatly influenced the manner in which the synthesis of complex organic molecules is approached. A wide variety of methods are now available for the formation of C(sp2)–C(sp2) bonds, and more recent work has focused on the use of C(sp3) electrophiles and nucleophiles. The use of secondary and tertiary alkyl nucleophiles in cross-coupling reactions remains an outstanding challenge because of the propensity of these alkyl groups to isomerize under the reaction conditions. Our research group seeks to develop efficient general methods to use secondary and tertiary organometallic nucleophiles in cross- coupling reactions. Further, we seek to extend this chemistry to the use of configurationally stable, optically active nucleophiles in stereospecific cross- coupling reactions. Such processes would enable the rapid generation of libraries of non-racemic drug candidates from a single optically active precursor. In this seminar, progress towards these goals will be presented.