The design of novel synthetic processes which maximize the construction of structural complexity while minimizing the number of synthetic operations is of monumental importance to the organic chemist. Modern synthetic methods require maximum efficiency by decreasing the total number of steps necessary to achieve the desired transformation in the highest yield possible. With economic and environmental factors looming large in today’s world of dwindling resources, the development of catalytic procedures, in particular asymmetric catalysis, has been the focus of intense study by a large number of research groups. With these issues as motivation, our group is interested in the development of new synthetic methods which combine the selective, atom economical properties of transition metal catalysis with the efficiency of tandem processes to construct a variety of complex natural products.

1. Enantioselective Chromium-Catalyzed Carbon-Carbon Bond Formation.
   The 1,2-anionic migration of a silyl group from carbon to oxygen, commonly referred to as the Brook rearrangement, has proven to be a versatile method for the synthesis of α-siloxy carbanions. However, the harsh anionic conditions required often limit the utility of this method in the late stage construction of complex natural products. This area of our research program is focused on the enantioselective construction of carbon-carbon bonds utilizing a chromium-catalyzed Brook rearrangement of acylsilanes. The mild generation of organochromium complexes allow for a wide array of in situ carbon-carbon bond forming reactions. Additionally, this program should further expand the scope of organochromium chemistry and its use in complex natural product synthesis. By harnessing the influence of chiral ligands bound to chromium, the entire process may be rendered enantioselective. The development of a general, asymmetric chromium-catalyzed Brook rearrangement can be applied to a variety of intriguing natural products, including the cytotoxic marine macrolide tedanolide.
   
   
2. Silicon-Mediated Mannich Cyclization/Schmidt Rearrangement Approach to Bicyclic Alkaloids.
   The nitrogen-containing bicyclic skeletal motif can be found in a vast array of structurally complex, biologically active natural products. Although, the corresponding 6-5 fused heterocyclic moiety is prevalent among a variety synthetic targets (i.e. martinellic acid and naphthyridiniomycin) methods of assembling this framework can be tedious and difficult to obtain stereoselectively. In fact, a direct, efficient, asymmetric entry into both the cis and trans octahydro-pyrrolo[3,2-c]pyridine has yet to be achieved. This area of our research program is focused on the development of a for the asymmetric construction of α-silyloxy azides, which is envisioned to initiate a unique tandem Mannich cyclization/Schmidt rearrangement cascade to access this difficult alkaloid bicycle with high levels of selectivity.