Development of an asymmetric trimethylenemethane cycloaddition reaction: application in the enantioselective synthesis of highly substituted carbocycles.

ABSTRACT: A protocol for the enantioselective [3+2] cycloaddition of trimethylenemethane (TMM) with electron-deficient olefins has been developed. The synthesis of novel phosphoramidite ligands was critical in this effort, and the preparation and reactivity of these ligands is detailed. The evolution of the ligand design, commencing with acyclic amine-derived phosphoramidites and leading to cyclic pyrrolidine and azetidine structures, is discussed. The conditions developed to effect an asymmetric TMM reaction using 2-trimethylsilylmethyl allyl acetate were shown to be tolerant of a wide variety of alkene acceptors, providing the desired methylenecyclopentanes with high levels of enantioselectivity. The donor scope was also explored, and substituted systems were tolerated, including one bearing a nit

SUBMITTER: Trost BM 

PROVIDER: S-EPMC3235052 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature