Atroposelective Total Syntheses of Naphthylisoquinoline Alkaloids with (P)-Configuration.

Abstract

Asymmetric total syntheses of naphthylisoquinoline alkaloids with a (P)-configuration are described. An atroposelective Suzuki-Miyaura reaction between naphthyl pinacol boronate and an aryl iodide bearing an (S)-2-(N-acetylamino)propyl group at the ortho-position using Pd(OAc)2 in the presence of SPhos and Ba(OH)2 provided the (P)-selective biaryl product as the major product without any external chiral sources. This biaryl product was converted into naphthylisoquinoline alkaloids with a (P)-configuration via stereoselective construction of the isoquinoline framework with the appropriate oxidation state and stereochemistry.