Efforts Toward Developing an Intramolecular Decarboxylative Allylation and Trapping of a Fischer Carbene Fragment

Indianapolis, IN

The cyclopentane core forms the backbone of many natural products and biologically active compounds, which makes any method to synthesize this class of molecules important. As we sought to develop a novel [4+1] annulation method that would be complementary to existing [3+2] cycloaddition pathways, we encountered a problem that led us to shift our approach. We had sought to use Fischer carbenes as the one-carbon fragment, and γ-methylidene-δ-valerolactones as the four-carbon fragment; these were to be joined via a decarboxylative allylation. After this approach proved problematic, we developed plans to establish an intramolecular variant of this reaction while maintaining the thematic elements of decarboxylative allylation and the use of Fischer carbenes. This new approach would offer a route to a complementary (but no less important) molecular architecture: spirocyclic heterocycles. It is predicated upon precedent that shows that intramolecular reactions are often successful in cases where the otherwise equivalent intermolecular reactions fail. This requires a more challenging synthesis of novel classes of Fischer carbenes, and our progress along these lines will be reported.