Ready Access to 6-Alkyl, 6-Phenyl, 5,6-Dialkyl, and 5-Alkyl-6-phenyl Substituted 1,2,3,4-Tetrahydroisoquinolines

Summary.  Readily available bicyclic enone precursors were used in a novel strategy for the synthesis of 6-mono- and 5,6-disubstituted tetrahydroisoquinolines (alkyl and phenyl in position 6, hydrogen and methyl in position 5). After 1,2-addition of the respective organometallic reagents to the enones, the crude intermediate alcohols were subjected to a dehydratization/aromatization procedure using the in situ generated triphenylmethyl cation. Overall yields obtained by this procedure were between 27 and 86%. Whereas the synthesis of N-benzyl protected 6-t-butyl-tetrahydroisoquinoline was successful, partial dealkylation occurred in the 5-methyl-6-t-butyl analogue. Some of the new N-benzyl tetrahydroisoquinolines were transformed into the corresponding unprotected heterocycles. Received March 22, 2001. Accepted May 22, 2001