Dr. Hawkins is a new investigator under the Presidential Young Investigator Award from the Organic and Macromolecular Chemistry Program. Under this will be studied the development of new organic synthetic methods using organometallic reagents. These will increase our capacity to synthesize efficiently the complex molecules used in modern medicine and agriculture. For the first project, metal carbonyls will be treated with organic substrates containing compatible nucleophilic and electrophilic sites. Addition of the nucleophilic moiety to the carbon of coordinated carbon monoxide should generate a metal nucleophile in proximity to the now pendant electrophilic moiety. The resulting complex will be set up for cyclization to a metallacycle, which may then reductively eliminate the desired selectively carbonylated organic product. Epoxy alcohols, epoxy amines, and sulphonium ylides will be examined as the bifunctional organic substrates. The anticipated reaction with epoxides corresponds to an aldol synthon where the starting epoxide's geometry controls the product's relative stereochemistry. Epoxy amines may accordingly give beta-lactams with stereochemical control The sulphonium ylide substrates may provide a new route to transition metal ketene complexes. The second project will involve the synthesis, resolution, and application of chiral dihaloboranes containing pi-bases. A substrate possessing both Lewis basic and pi-acidic sites such as an alpha, beta-unsaturated ester should bind to these catalysts via simulataneous synergistic Lewis acid-base and pi-acid base interactions. The constraints imposed by this two-point binding may cause one face of the olefin to be selectively blocked. Accordingly, the other face will be open to approach by reagents. Dienes will be tested here; displacement of the corrdinated pi-base by an incoming diene may result in an asymmetric Diels Alder reaction. No longer containing a pi-acid for a second binding point, the cyclohexene product should be displaced from the catalyst by the two-point binding starting material. The catalyst structures will be varied in order to optimize this enzyme-like scenario. Methods for the stereospecific vicinal bismethylation of a double bond will be explored in a third project. Coordination of an olefinic substrate to a heterobimetallic bis-mu-methylene complex may lead to insertion into one of the metal-carbon bonds forming a 1,3-dimetallacyclohexane. This species may then reductively eliminate a metallacyclopentane which can be protonolyzed to the desired bismethylated product. Mo-Co and Mo-Fe complexes will be studied in this vein.
