Alkylation of N-boc-1,2,3,4-tetrahydroisoquinolines in the 1-position and its application to the synthesis of isoquinoline alkaloids

Boc-protected 1,2,3,4-tetrahydroisoquinolines 2 can be lithiated with t-butyllithium in the presence of N,N,N',N',-tetramethylethylenediamine. Reaction of the anion with alkyl halides provides 1-alkyl N-Boc-1,2,3,4-tetrahydroisoquinolines in 67–71% yield. The protecting group is easily removed in high yield with trifluoroacetic acid. The alkaloids salsolidine ( 8 ) and laudanosine ( 11 ) were synthesized in racemic form using this method.