Asymmetric Synthesis of Unnatural (-)-Gracilamine

We describe a concise enantioselective synthesis of (-)-gracilamine from N-nosyl-tyrosine methyl ester in 10 steps. A tyrosine-derived oxazolidine functions as both a protecting group and a chiral auxiliary to guide an early oxidative dearomatization process that establishes a crucial quaternary carbon and the desymmetrization of a prochiral dienone. The synthesis is completed by a cascade involving a Fukuyama nosyl deprotection/1,4-addition, an azomethine ylide cycloaddition, an oxidative fragmentation, and a double reductive amination. This synthesis highlights the importance of environmentally benign hypervalent iodine reagents as powerful tools in the synthesis of complex structures.