Multicomponent domino process to oxa-bridged polyheterocycles and pyrrolopyridines, structural diversity derived from work-up procedure

Novel three-component domino processes to polyheterocycles are developed. Reaction of an allylamine, an aldehyde and an alpha -isocyanoacetamide in methanol at room temp. provides an efficient access to an oxa-bridged tricycle as a single diastereoisomer. In this one-pot process, one C-N, one C-O and three C-C bonds are formed with concomitant creation of five asym. centers. While isolable, the oxa-bridged tricycles can be cleanly in-situ fragmented to pyrrolopyridines under acidic conditions (trifluoroacetic acid, -78 DegC), providing thus an unusual work-up derived structural diversity. The operational simplicity and excellent chem. yield make these novel heterocycle syntheses valuable in diversity-oriented high throughput synthesis. [on SciFinder (R)]