Base-Mediated Cascade Cyclization: Stereoselective Synthesis of Benzooxazocinone.

A new strategy for the synthesis of the oxa-azabicyclo[3.3.1]nonane subunit, a component of the naucleamide E core structure, has been developed. This annulation reaction between 1-substituted 3,4-dihydroisoquinolines and coumarin derivatives conveniently affords the oxa-azabicyclo[3.3.1]nonane framework via a base-mediated cascade cyclization under aqueous conditions. The value of this work lies in the efficient formation of the oxa-azabicyclo[3.3.1]nonane skeleton via a process whereby all the C-C, C-O, and C-N bond formations occur in a single chemical operation. In addition, the subsequent ring opening of these compounds furnished pyridoisoquinoline derivatives.