James R. Manning

Catalytic C–H functionalization by metal carbenoid and nitrenoid insertion

Novel reactions that can selectively functionalize carbon–hydrogen bonds are of intense interest to the chemical community because they offer new strategic approaches for synthesis. A very promising ‘carbon–hydrogen functionalization’ method involves the insertion of metal carbenes and nitrenes into C–H bonds. This area has experienced considerable growth in the past decade, particularly in the area of enantioselective intermolecular reactions. Here we discuss several facets of these kinds of C–H functionalization reactions and provide a perspective on how this methodology has affected the synthesis of complex natural products and potential pharmaceutical agents.

One-Pot Synthesis of Highly Functionalized Pyridines via a Rhodium Carbenoid Induced Ring Expansion of Isoxazoles

A concise one-pot synthesis of highly functionalized pyridines has been developed. The first step in the reaction sequence is the formal insertion of rhodium vinylcarbenoids across the N-O bond of isoxazoles. Upon heating, the insertion products undergo a rearrangement to give 1,4-dihydropyridines. DDQ oxidation then affords the corresponding pyridines in 31-84% yield. The process has proven general with a range of carbenoid and isoxazole components and represents a unique disconnection strategy for the synthesis of functionalized pyridines.

1-Naphthyl and 4-indolyl arylalkylamines as selective monoamine reuptake inhibitors

A series of enantiomerically pure 1-naphthyl and 4-indolyl arylalkylamines were prepared and evaluated for their binding affinities to the monoamine transporters. The two series of enantiomers displayed considerable differences in binding selectivity between the monoamine transporters, leading to the design of (S)-4-(3,4-dichlorophenyl)-4-(1H-indol-4-yl)-N-methylbutan-1-amine as a potent inhibitor for the dopamine and serotonin transporters.