HYDROFUNCTIONALIZATION OF ALKENES BY HYDROGEN-ATOM TRANSFER

摘要

The synthesis of tetrasubstituted carbon atoms remains a challenging problem. In cases wherein one of the four substituents is a tertiary carbon (i.e., bearing a hydrogen atom), application of an alkene hydrofunctionalization transform frequently provides a good solution. In a retrosynthetic sense, one or two stereocenters and a functional group can be retrosynthetically excised to generate a prochiral alkene, a single hydrogen, and a reagent or reactive fragment FG (Scheme 1). Therefore, the retrosynthetic hydrofunctionalization transformation ranks high in a first pass analysis of strategies that remove complexity;1 its peers in Corey's transform hierarchy include C-H functionalization and skeleton bond cleavage. The incorporation of tetrahedral carbon atoms (sp3-hybridized) into drug candidates has recently grown compared to their planar, sp2-hybridized counterparts with the understanding that high fraction sp3 scaffolds progress further than compounds containing lower numbers of sp3 centers.2 Therefore, new methods that can assemble sp2-sp3 or sp3-sp3 bonds are in high demand.