Intramolecular palladium-catalyzed cyclization of alkenylboronate prepared from hydroboration of terminal acetylene and its application to the stereoselective synthesis of (E)-doxepin

The hydroboration of 2-[(2-ethynylphenyl)methoxy]-1-iodobenzene with bis(pinacolato)diboron in the presence of palladium catalyst and followed by consecutive oxidative addition, cis-cyclocarbopalladation, and cis-β-elimination could give highly stereoselective exocyclic alkenylboronate ester. The following cross-coupling of the exocyclic alkenylboronate ester with 2-bromo-N,N-dimethylacetamide in the presence of palladium catalyst and followed by LAH reduction gives (E)-doxepin in fair yields.