Synthesis of Tetrahydroisoquinolines and Tetrahydropyridines from Oxaziridines

Significance

Reported here is the synthesis of tetrahydroisoquinolines 2 from N-sulfonyloxaziridines 1 via Cu-catalyzed C-H activation followed by reductive amination. The reaction is tolerant of both EDG and EWG on both aromatic fragments (R^¹ and R^²). The methodology was extended to include substrates 3 and 6 bearing aliphatic linkers which, upon treatment with acid, generate enamides 5 and piperidones 8, respectively. A mechanism involving coordination of the copper catalyst to the oxaziridine followed by homolytic N-O bond cleavage and cyclization to form a hemiaminal intermediate is proposed.