Chirality Transfer in Electrophilic Reactions of Hydrovinylation Adducts

Abstract

As a result of new regulatory requirements and a deeper understanding of the role of chirality in biological systems, the modern pharmaceutical industry has become dependent on chemical processes which can selectively produce enantiopure compounds without wasteful resolutions. The asymmetric hydrovinylation reaction has been demonstrated to yield a number of popular NSAIDs with exceptionally high selectivity. The major thrust of this project was to examine how well chirality could be transferred from an asymmetric center installed by the hydrovinylation to a new chiral center formed with an achiral electrophilic reagent. The highest levels of selectivity were observed for dihydroxylation and oxymercuration reactions, both of which employed sterically demanding third row transition metal reagents. In addition to investigating selectivity, the photochemical Barton reaction was examined as a route to functionalize methyl groups that result from the hydrovinlation of terminal ole ns. Preliminary scouting experiments suggest the Barton reaction may provide a viable route to functionalization.