Diastereoselective tandem 6-exo carbolithiation intramolecular ring opening in (-)-8-aminomenthol-derived perhydrobenzoxazines. A new synthesis of enantiopure 1-substituted tetrahydro isoquinolines and 2-azabenzonorbornanes

Aryllithiums prepared by bromine-lithium interchange in chiral 2-(o-bromoph enyl)-substituted perhydro-1,3-benzoxazines participate in the intramolecul ar 6-exo carbolithiation reaction with unactivated double bonds attached to the nitrogen substituent of the heterocycle. When the reaction time is ext ended or no TMEDA is used, the cyclized lithium intermediates react intramo lecularly with the N,O-acetal system leading to 2-azabenzonorbornane deriva tives. The reactions are highly stereoselective and constitute a high-yield ing synthesis of enantiopure 4-substituted tetrahydroisoquinolines or 7-sub stituted 2-azabenzonorbomanes.