Application of thio chemistry for the synthesis of nitrogen heterocycles

ORGN 7

Albert Padwa, chemap@emory.edu and Andrew C. Flick, acflick@emory.edu. Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, GA 30322
The synthesis of the cylindricine family of alkaloids requires the formation of a challenging quaternary carbon center embedded within a complex nitrogen-containing tricyclic unit. As part of our efforts to develop a general approach towards the construction of such alkaloids, we have utilized a novel tandem Michael addition/intramolecular dipolar cycloaddition cascade sequence. Condensation of 2,3-diphenylsulfonyl-1,3-butadiene with an appropriately substituted oxime results in the formation of an oxa-azabicyclo heptane derivative via the above sequence of reactions. Reductive N-O bond cleavage leads to the formation of either a 2,2-disubstituted-4-piperidone or a 7-indolizidone unit which was subjected to further synthetic manipulations. Several examples of this methodology will be presented as well as an application of the protocol for a concise total synthesis of the marine alkaloid cylindricine C