Lithium bromide-promoted three-component synthesis of oxa-bridged tetracyclic tetrahydroisoquinoline derivatives

Heating a toluene soln. of an alpha -(isocyano)acetamide deriv., an aldehyde and a 3-(2-aminophenyl)propenoic acid (aniline) deriv. in the presence of lithium bromide at 60 Deg provides an oxa-bridged tetracyclic tetrahydroquinoline in good to excellent yield as a mixt. of two separable diastereoisomers. In this one-pot multicomponent reaction, one C-N, one C-O and three C-C bonds are formed with concomitant creation of five asym. centers and three heterocycles. Fragmentation of epoxy-tetrahydroquinoline an under mild acidic conditions affords a 4,6-phenanthroline deriv. The multicomponent reaction of 2-isocyano-1-(4-morpholinyl)-3-phenyl-1-propanone with heptanal and 3-(2-aminophenyl)-2-propenoic acid Me ester gave (1R,2S,4aS,5S,10bS)-rel-5-hexyl-1,5,6,10b-tetrahydro-2-(4-morpholinyl)-3-(phenylmethyl)-2H-2,4a-epoxybenzo[f][1,7]naphthyridine-1-carboxylic acid Me ester (major product). [on SciFinder (R)]