Synthesis of (±)-glaucine and (±)-neospirodienone via an one-pot Bischler-Napieralski reaction and oxidative coupling bya hypervalent iodine reagent

Condensation of 3,4-dimethoxybenzeneethanamine (3d) and various benzeneacetic acids, i.e., 4a-e, via a practical and efficient one-pot Bischler-Napieralski reaction, followed by NaBH4 reduction, produced a series of 1-benzyl-1,2,3,4-tetrahydroisoquinolines, i.e., 5a-e, in satisfactory yields (Scheme 3). Oxidative coupling of the N-acyl and N-methyl derivatives 6a-e of the latter with hypervalent iodine ([IPh(CF3COO)(2)]) yielded products with two different skeletons (Scheme 4). ne major products from N-acyl derivatives 6a-c were (+/-)-N-acylneospirodienones 2a-c, while the minor was the 3,4-dihydroisoquinoline 7 (+/-)-Glaucine (1), however, was the major product starting from N-methyl derivative 6e. Possible reaction mechanisms for the formation of these two types of skeleton are proposed (Scheme 5).