The Synthesis of 5-Amino-dihydrobenzo[b]oxepines and 5-Amino-dihydrobenzo[b]azepines via Ichikawa Rearrangement and Ring-Closing Metathesis

J Org Chem. 2016 Oct 7;81(19):9046-9074. doi: 10.1021/acs.joc.6b01691. Epub 2016 Sep 20.

Abstract

The combination of Ichikawa's rearrangement and a ring-closing metathesis reaction of allyl carbamates is presented as a method for the preparation of 5-amino-substituted 2,5-dihydro-benzo[b]oxepines, 2,5-dihydro-benzo[b]azepines, and 2,5-dihydro-benzo[b]thiepins. It was demonstrated that the use of nonracemic allyl carbamates enables the synthesis of enantioenriched benzo-fused seven-membered heterocycles. Finally, it was shown that further functionalization of the obtained structures allows access to pharmacologically active 5-amino-substituted 2,3,4,5-tetrahydro-1-benzo[b]oxepine scaffolds.

Publication types

  • Research Support, Non-U.S. Gov't