Advancing the Morita-Baylis-Hillman chemistry of 1-formyl--carbolines for the synthesis of indolizinoindole derivatives

Abstract

The chemistry of the Morita-Baylis-Hillman adducts of 1-formyl-beta-carbolines has been extended for obtaining indolizinoindole derivatives which mimic the harmicine and homofascaplysin frameworks. Adduct of N-substituted methyl 1-formyl-9H-beta-carboline-3-carboxylate upon bromination followed by aqueous work up results in formation of indolizinoindole derivative. On the other hand N-substituted 1-formyl-9H-beta¢-carboline yielded similar product in one-pot via DABCO-promoted reaction of activated alkene. Alternatively the DMAP-mediated Morita-Baylis-Hillman reaction of N-substituted methyl 1-formyl-9H-beta-carboline-3-carboxylate with cycloalkenones yielded adducts, which cyclizes intramolecularly in the presence of PBr3 to yield compounds with homofascaplysin framework. In contrast DMAP-mediated reaction of N-substituted 1-formyl-beta-carboline with cyclohexenone directly gave product with similar framework in a single step.