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This grant described our efforts to use conformationally-defined peptides to control the stereoselectivity of nitroalkane reactions. Our efforts in the last year have been to create new catalysts that will show enhancements of selectivity, gain insight into mechanistic details, and expand the substrate scope for optimized catalysts. Optimization of catalyst design revolves around modifications to their hydrogen bonding and structural aspects in the course of modular synthesis. Initial designs relied on largely commercially available amino acids, so further modifications require more involved syntheses. We have created a series of amino acids that position a collection of hydrogen bonding groups at various distances from the peptide backbone. Incorporation of these residues into complete peptides will permit investigation of the catalytic properties. In a similar way, structural changes to the peptide backbone are being probed for enhancements to selectivity. We have synthesized the appropriate amino acid derivatives that should maintain the pre-organized fold of the catalyst, but introduce additional steric constraints to more tightly organize the assembly of the transition state.

Mechanistic explorations involve the determination of absolute stereochemistry and investigation of transition state structure. We have initiated a stereoselective synthesis of our product using well-established Seebach oxazolidinone chemistry. We have completed the synthesis of a transition state mimic that has the same structural aspects and placement of electron density found in our presumed transition state. We will begin to probe the long-range interactions of our transition state mimic with the catalyst through NMR. This past year's progress has been slightly disrupted by construction in the science complex at Holy Cross, with a new building being dedicated for the Department of Chemistry in January 2009. While this new building will provide exceptional research space for individual groups, each lab is currently being shared by two research groups until renovations on the older building are complete in January 2010. This past year, two students have been involved in this project, with one being directly funded from this grant. Ideally, the new additions to department space will permit more student involvement and increased accessibility to research.