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 (3), an aldehyde (4) and an alpha-isocyanoacetamide (5) in methanol at room temperature provides an efficient access to oxa-bridged tricycle (1) 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 (1) can be cleanly in-situ fragmented to pyrrolopyridines (2) under acidic conditions (trifluoroacetic acid, -78degreesC), 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. (C) 2002 Elsevier Science Ltd. All rights reserved.