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 α-isocyanoacetamide () in methanol at room temperature provides an efficient access to 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 asymmetric centers. While isolable, the oxa-bridged tricycles () can be cleanly in-situ fragmented to pyrrolopyridines () under acidic conditions (trifluoroacetic acid, −78°C), providing thus an unusual work-up derived structural diversity. The operational simplicity and excellent chemical yield make these novel heterocycle syntheses valuable in diversity-oriented high throughput synthesis.