Intramolecular Michael reactions of vinylnitroso compounds and studies directed towards an asymmetric total synthesis of the Stemona alkaloid stemofoline

We have developed novel methodology that produced the first examples of intramolecular 1,4-conjugate additions of carbon and hetero nucleophiles to vinylnitroso compounds. Combining several new methods developed in these labs, we have been able to access the requisite precursors and optimize the reaction conditions for these transformations. Namely, we have shown that a vinylnitroso species generated from the corresponding alpha-chlorosilyl-oximes using fluoride ion, interacts with a tethered nucleophile in a 1,4-manner producing a variety of carbocyclic and heterocyclic products. Recognizing that this methodology allows us facile entry into the stemofoline alkaloid skeleton, we have attempted to apply it to an asymmetric total synthesis of this metabolite. In the course of these studies new methodology for oxidation of alpha-hydroxy-beta-ketoesters to alpha-diazo-beta-ketoesters emerged, thus allowing us to generate some of the intermediates required to advance the synthesis.