Synthesis of enantiopure mono- and disubstituted tetrahydroisoquinolines by 6-exo radical cyclizations

2-(o-Bromophenyl)-3-allyl- and 2-allyl-3-(o-bromobenzyl)-substituted perhydrobenzoxazines, derived from (−)-8-amino menthol, readily cyclized stereoselectively by reaction with tributyltin hydride in the presence of AIBN. The cyclization compounds were transformed into enantiopure 4-alkyl tetrahydroisoquinolines by reductive ring opening of the N,O-acetal moiety with lithium aluminum hydride. Enantiopure 1,4- and 3,4-dialkyl-substituted tetrahydroisoquinolines were also prepared by reaction of the cyclized compounds with methylmagnesium iodide and subsequent elimination of the menthol appendage.