Carbocyclic and heterocyclic rings are present in nearly all pharmacologically active compounds. Consequently, the development of highly selective, yet general procedures for the synthesis of various ring systems is an essential aspect of synthetic organic chemistry. The primary goal outlined in this proposal is the invention of useful new strategies for selective generation of carbocycles and heterocycles by reductive cyclization processes. Samarium diiodide (SmI2) is a remarkably versatile reducing agent, one that can adequately serve as a template for many of the processes proposed. Two distinct areas have been targeted for study. First, continued development of cyclization reactions promoted by SmI2 as well as other reductants will be pursued, providing entry into highly functionalized carbocycles and heterocycles difficult to access by more conventional approaches. A survey of the scope of difunctional organic substrates suitable for reductive cyclization will be initiated, and stereoselectivity in these processses will be determined. It is aniticipated that several novel approaches to carbocycles and heterocycles will be uncovered as a result of these studies, and that new methods for formation of carboncarbon bonds will also emerge. Approaches to highly functionalized, chiral, non-racemic carbocycles and heterocycles are also outline. The second major area of proposed research involves SmI2-promoted reductive coupling of various organic substrates with transition metal catalysts or stoichiometric complexes, establishing unique carbon-carbon bond-forming transformations. Oxidative-reductive transmetalation processes incorporating organic substrates, a reductant like SmI2, and Pd(0) or Ni(0) catalysts will constitute one aspect of the initial studies. Reaction of cationic transition meal complexes with suitable elecrophiles in the presence of a reductant like SmI2 will comprise the second research area. These combinations of reagents will allow access to new or imporoved reactivity patterns for selective formation of carbon-carbon bonds, and contributions to both acyclic stereochemical control as well as efficient carbocyclic generation are expected.
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