Advancing the Morita-Baylis-Hillman Chemistry of 1-Formyl-β-carbolines for the Synthesis of Indolizino-indole Derivatives

The chemistry of the Morita-Baylis-Hillman adducts of 1-formyl-beta-carbolines has been extended for obtaining indolizino-indole derivatives which mimic the harmicine and homofascaplysin frameworks. Adducts of N-substituted methyl 1-formyl-9H-beta-carboline-3-carboxylate yield indolizino-indole derivatives upon bromination followed by aqueous workup. On the other hand, N-substituted 1-formyl-9H-beta-carbolines give rise to similar products in a one-pot DABCO-promoted reaction of activated alkenes. Alternatively, the DMAP-mediated Morita-Baylis-Hillman reaction of N-substituted methyl 1-formy1-9H-beta-carboline-3-carboxylate with cycloalkenones yields adducts that cyclize intramolecularly in the presence of PBr3 to yield compounds with the homofascaplysin framework. In contrast, the DMAP-mediated reaction of N-substituted 1-formyl-beta-carboline with cyclohexenone directly gives a product with similar framework in a single step.