Oxazinoisoquinoline Synthesis via the Unusual Reactivity of Aminomethylnaphthols

Significance

Reported is the synthesis of oxazinoisoquinolines 4 by the condensation of amino­methylnaphthols 2 and 3 with dihydroisoquinolines 1. Initial experimentation (conditions A) established the unexpected formation of the dihydroisoquinoline as a single diastereomer, as confirmed by NOE studies. Further optimization (conditions B) revealed that the use of microwave irradiation reduces reaction times to afford the desired products in enhanced yield. When enantio­enriched 3 was employed, racemic 4 was produced, supporting the generation of an achiral intermediate, such as ortho-quinone methide 5, in the proposed reaction mechanism.