SYNTHESIS OF 1-SUBSTITUTED 1,2,3,4-TETRAHYDROISOQUINOLINES FROM ENAMINO KETONES

The reaction of the N-acylated enamino ketones 4a d with trifluoroacetic acid, TMS triflate, or Lewis acids leads to the 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines 5a-d in 84 to 94% yield. The enamino ketones 4f-i can only be cyclized with trifluoromethanesulfonic acid to the 1,2,3,4-tetrahydroisoquinolines 5f-i in 75-84% yield. For the synthesis of 5e from the enamino ketone 4e carrying the benzyloxycarbonyl group TMS triflate is the best mediator (93%). The trichloromethylcarbonyl group in 5 can easily be transformed into a methoxycarbonyl group by treatment with K2CO3 in methanol to give 6 in 83 - 90% yield.