The major difficulty in enantioselective synthesis of cocaine and cocaine analogues is the requirement that the cocaine C-2 and C-3 substituents have a cis relationship.  As a consequence most cocaine analogues are modifications of the C-2 and C-3 substituents that are derived from cocaine.  We describe here the first enantioselective synthesis of C-1 cocaine analogues from a masked oxo-sulfinimine.  This method uses a novel Lewis acid catalyzed [3 + 2] cycloaddition reaction of an a,b-unsaturated pyrrolidine nitrone to prepared a tricyclic isoxazolidine, which controls the stereochemistry at C-2 and C-3.  A novel Palladium and base-promoted rearrangement of N-Me methanesulfonate salts of isoxazolidine to brideged bicyclic[4.2.1]isoxazolidines was discovered.  Details of the synthesis will be presented

First enantioselective synthesis of C-1 cocaine analogs using sulfinimine (<i>N</i>-sulfinyl imines)

244th National Meeting (2012)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.

First enantioselective synthesis of C-1 cocaine analogs using sulfinimine (N-sulfinyl imines)