New Transformations in the Transition-Metal Catalyzed Hydrofunctionalization of Alkynes

Abstract

Hydrofunctionalization reactions are very useful transformations of unsaturated compounds and their development has been a major focus of research in the field of transition metal catalysis. These reactions allow the rapid build up of molecular complexity of simple substrates in a single transformation and recently significant progress has been made in the development of regio-, stereo- and enantioselective hydrofunctionalizations. Here we describe the development of three reactions involving transition metal-catalyzed hydrofunctionalization. The first is the hydroallylation of alkynes furnishing skipped dienes. Regioselective hydroallylation of nonsymmetrical internal alkynes was achieved through the installation of polar functional group in the propargylic position. This resulted in inductive polarization of the alkyne bond allowed for the regioselective synthesis of trisubstituted alkenes. The second reaction described is the diastereodivergent hydroarylation of alkynes. Both Z- and E-styrenes are accessed from one set of starting materials using synergistic Cu/Pd catalysis. The reaction proceeds through tandem Sonogashira cross-coupling followed by Z-selective semireduction and isomerization, where the diastereoselectivity is determined by the stoichiometry of a methanol additive. The last reaction describes the reductive three-component coupling of terminal alkynes, aryl halides and pinacolborane using synergistic Cu/Pd catalysis. Copper-catalyzed hydroboration followed by hydrocupration generates a key heterobimetallic complex, subsequent palladium-catalyzed cross-coupling with aryl halides provides benzylic alkyl boronates. Investigation of other electrophiles and enantioselective variants is currently underway.