Exploration of Synthetic Pathways to Quaternary Carbon Stereocenters and Fused Ring Systems via Birch Reductions

The Birch reduction – alkylation is an effective way to form all-carbon quaternary centers from inexpensive commercially available starting material. When coupled to complementary reactions such as the Rauhut-Currier or Mizoroki-Heck, complex drug-like structures can be rapidly formed. We have developed and reported the first example of a Lewis acid mediated Rauhut-Currier reaction as well as the first examples of an enantioselective desymmetrizing aryl vinyl Mizoroki-Heck reaction to form quaternary carbon stereocenters. We report efforts toward cyanthiwigin F via a decarboxylative allylation as well as an enantioselective Birch – Heck sequence to make 6-5-6 and 6-6-6 carbocyclic and heterocyclic systems. In all of these examples the Birch reduction alkylation has been the key step and we have demonstrated broad applicability and the use of some of the most complex alkylating agents to date