AmericanChemicalSociety.com

            This is the second report for the PRF grant entitled “Hydrogen bonding peptides as asymmetric organocatalysts.”  This grant described our efforts to use conformationally-defined peptides to control the stereoselectivity of nitroalkane reactions.  Our efforts this year have been to expand the substrate scope of these catalysts and construct catalysts using new scaffolds that could demonstrate increased selectivity or substrate compatibility.

            Having developed organocatalysts for the enantioselective additions of nitroalkanes to vinyl ketones, we have turned our attention to alternate substrates and reactions.  We have extended our investigations to a variety of analogous enolizable nucleophiles in anticipation of similar hydrogen bonding interactions with the catalysts.  Additional conjugate accepters capable of making hydrogen bonding interactions with our catalysts have been employed and the selectivities tend to track proportionally with the rate sof the reactions.  In addition we have expanded the scope of these reactions to include cyclopropanations derived from similar conjugate addition of bromo-nitroalkanes to vinyl ketones.  With hydrogen bonding catalysts that can interact with oxyanions such as nitronates it was a small step to probe the interactions with carboxylate anions and their role in the kinetic resolution of a-alcohol acylation.

            Previous catalysts have relied on a library approach to produce a variety of catalysts and determine which is the most effective in the specific reaction.  A more designed approach has begun that relies on the construction of new receptors capable of making specific interactions with anionic guests.  These catalysts have shown the ability to bind to carboxylates and nitronates following a linear relationship of binding affinity and the number of hydrogen bonds.  Additionally these receptors have been shown to catalyze the nitroaldol reaction in a manner proportional to the binding strength.  These designed catalysts are being employed in a variety of reactions that rely on the association with and stabilization of oxyanion intermediates.           In January 2010 the new integrated science complex was dedicated at Holy Cross.  This provides truly state-of-the-art classrooms, teaching labs and research space for the Department of Chemistry.  This grant has been instrumental in providing the resources to outfit the materials and chemicals for the progression of this work.  This past year, two students have been involved in this project, with one being directly funded from this grant.  The undergraduate researchers have been involved in all aspects of this project, from the design of targets, literature searches, synthetic procedures and purifications, and analysis of selectivities.