AREAS I and II.
A Formal [3 + 3] Cycloaddition or Annulation Strategy for Natural Product Synthesis.
We have developed a formal [3 + 3] cycloaddition reaction that can construct complex dihydropyranyl and dihydropyridinyl heterocycles from simple a,b-unsaturated iminiums and 1,3-dicarbonyl equivalents such as vinylogous amides or other. This reaction proceeds through a tandem process consisting of a Knoevenagel condensation followed by a 6p-electron electrocyclic ring-closure of the 1-oxa- or 1-azatriene intermediates. The net result of this step-wise or formal cycloaddition reaction is the formation of two s-bonds along with a new stereocenter adjacent to the heteroatom. The new stereocenter can be controlled using chiral vinylogous amide, and an intramolecular variant of this reaction has also been recently developed. We are currently applying this strategy toward syntheses of a variety of natural products shown below.
I. A Formal [3 + 3] Cycloaddition Approach to Oxa-Heterocyclic Natural Products.
II. A Formal Aza-[3 + 3] Cycloaddition Strategy for Total Syntheses of Alkaloids.
