Synthesis of 4-aryl-2-methyl-1,2,3,4-tetrahydroisoquinolines via Pummerer-type cyclization of N-(arylmethyl)-N-methyl-2-aryl-2-(phenylsulfinyl) acetamides

Abstract

The synthesis of 4-aryl-2-methyl-1,2,3,4-tetrahydroisoquinolines ( Trifuoroacetic anhydride induced cyclization of the sulfoxides 10 at ambient temperature readily provided 4-aryl-2-methyl-4-(phenylsulfanyl)-1,2,3,4-tetrahydroisoquinolin-3-ones (11) in almost quantitative yield. Subsequent reductive removal of the phenylsulfanyl group from 11 with NaBH4-NiCl2 followed by the reduction of the lactam function of the resulting 4-aryl-2-methyl-1,2,3,4-tetrahydroisoquinolin-3-ones (15) furnished the title products 16 in excellent yields. This conversion offers a total synthesis of ()cherylline 16g, an amaryllidaceae alkaloid.