The objectives of this work are to develop new reagents and methods for the construction of carbon-carbon and carbon-heteroatom bonds for use in the synthesis of medically useful compounds. The proposed research is divided into three areas: 1) The use of low valent early transition metal reagents for the intramolecular coupling of nitriles with ketones/aldehydes, olefins, acetylenes and other nitriles. In addition, we plan to similarly investigate the intramolecular coupling of ketones/aldehydes with olefins and acetylenes. It is proposed that the above-mentioned reactions should allow for the preparation of a variety of stereospecifically functionalized carbocycles (of many ring sizes) by subsequent transformations of the initially formed metallacycles; 2) The synthesis of 2-oxy and 2-aza metallacyclopentanes (of titanium and zirconium will be executed and their reaction chemistry will be studied. It is believed that these metallacycles will be of general use for the construction of Gamma-functionalized amines and alcohols as well as for the production of lactones, lactams and other functional group arrays ubiquitous in physiologically active molecules; 3) The preparation and study of Beta-alkoxy and Beta-amido carbanions is proposed. These species are useful both as vehicles for the production of the above-described heterometallacyclopentanes and as reagents for carbon-carbon bond formation for use in organic synthesis.
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