Copper-catalyzed regio and diastereoselective three component C-N, C-C and C-O bond forming reaction: oxidative sp3 C-H functionalization

A highly regio and diastereoselective copper catalyzed three component reaction of tetrahydroisoquinolines ( THIQs), aldehydes, and naphthols to furnish naphthoxazine derivatives under mild conditions was developed. The initial generation of iminium ions followed by the nucleophilic attack of naphthol presumed to deliver 15-phenyl-7a,12,13,15-tetrahydronaphtho[1',2':5,6][1,3]oxazino[2,3-a] isoquinoline derivatives. The reaction ensured the formation of C-C, C-N and C-O bonds in a one-pot reaction to produce ring fused N,O-acetals in good yields. The three component reaction, the inexpensive copper catalyst in the absence of a co-oxidant/additive and the direct regioselective oxidative sp(3) C-H functionalization are the attractive features of this approach. The preliminary photophysical properties obtained for selected compounds were presented.