Preparation of substituted tetrahydroisoquinolines by Pd(II)-catalyzed NH2-directed insertion of Michael acceptors into C-H bonds followed by NH2-conjugated additions

Abstract

3,3-Disubstituted tetrahydroisoquinolines are prepared in one step from Michael acceptors and 2-phenylethylamines under Pd catalysis and Ag2CO3 as an oxidant. Presumably, activation of an ortho C-H bond of the aromatic ring with Pd(II) is directed by the primary amine to form a palladacycle. Insertion of the olefin, subsequent conjugated addition of the amine, and reductive elimination of Pd(0) affords the expected products. Silver carbonate is not necessary when 2-phenylethylamines are converted previously to N-benzoyloxy-2-phenylethylamines.