Novel methodologies via the catalytic carbocupration of alkynoates and the total synthesis of (+)-aspergillide B.

摘要

This dissertation highlights three novel reactions that involve an initial trimethylsilyl trifluoromethanesulfonate (TMSOTf) mediated catalytic carbocupration of alkynoates. In addition to finding that a specific proton source (TFA) provides (Z)-substituted alpha,beta-unsaturated esters, we established that the intermediate TMS allenolate could undergo highly diastereoselective carbon-carbon, deuterium, and silyl bond forming reactions in a single flask. Also, we have been successful in vicinally functionalizing ynoates via the initial carbocupration followed by a secondary electrophilic capture of the TMS allenolate intermediate. Not only did we provide disubstituted and trisubstituted alkenes, we report the synthesis of a tetrasubstituted alkene in high level of diastereoselectivity and yield as well. Seeing that organocuprate additions to activated multiple bonds are an important tool in synthetic organic chemistry, it should be apparent that these catalytic, diastereoselective carbocupration reactions should be useful when forming substituted alkenes in organic synthesis.;The second part of this dissertation focuses on the successful total synthesis of (+)-aspergillide B. It belongs to a family of biologically active natural products that contain C-glycoside subunits and a trans-olefin as part of the macrocyclic structure. The synthesis is best summarized by the highly diastereoselective oxocarbenium allylation to forge the alpha-C glycoside subunit, followed by a cross metathesis and Yamaguchi macrolactonization.