Multicomponent synthesis of epoxy-tetrahydronaphthyridine and structural diversification by subsequent fragmentation

Three-component reaction of an α-isocyanoacetamide , an homoallylamine and an aldehyde in methanol at room temperature provides oxa-bridged tricycle in good to excellent yield as a mixture of two separable diastereoisomers. In this one-pot multicomponent process, one C–N, one C–O and three C–C bonds are formed with concomitant creation of five asymmetric centers and three rings. Fragmentation of epoxy-tetrahydronaphthyridine affords differentially substituted 5,6,7,8-tetrahydro-1,7-naphthyridine (, ) depending on the reaction conditions, providing thus additional structural diversity. A one-pot three-component synthesis of 5,6,7,8-tetrahydro-1,7-naphthyridine () from , and is also documented.