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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM038068-01
Application #
3294068
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1987-03-01
Project End
1990-02-28
Budget Start
1987-03-01
Budget End
1988-02-29
Support Year
1
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Indiana University Bloomington
Department
Type
Schools of Arts and Sciences
DUNS #
006046700
City
Bloomington
State
IN
Country
United States
Zip Code
47402