Novel synthetic organic methodology is proposed for the hydride-mediated conjugate reduction of Alpha,Beta-unsaturated carbonyl functionality catalytic in the hydride reagent. Hydride conjugate reduction, a transformation of potentially general utility in the stereospecific synthesis of medicinally important organic molecules, remains an unresolved problem in organic synthesis. The use of hydride reducing agents generated catalytically from inexpensive molecular hydrogen is unprecedented in organic synthesis, and represents a significant conceptual advance in organic reduction technology. The proposed copper (I) based chemistry is expected to be highly chemoselective and regioselective, amenable for use on highly functionalized substrates typical in natural products synthesis. The development of more reactive hydride sources is proposed to expand the range of reducible functionality to include sterically hindered and electronically deactivated functional groups, providing general methodology for achieving selective hydride reductions catalytically using molecular hydrogen. This transformation, in stoichiometric form, will further provide a protocol for reductive alkylation of unsaturated carbonyl compounds.
