Studies in the synthesis of camptothecin. An efficient synthesis of 2,3-dihydro-1H-pyrrolo[3,4-b]quinoline

Abstract

An efficient regioselective synthesis of 2,3-dihydro-1H-pyrrolo[3,4-b]quinoline (3), a key intermediate in the synthesis of camptothecin, has been developed. The synthesis, which has been extended to a number of analogues, involves an acid-catalysed Friedländer condensation in the absence of a solvent. Base-catalysed condensation was shown to lead predominantly to the isomeric 2,3-dihydro-1H-pyrrolo[3,2-b]quinoline (10). The relative stabilities of the enols and enolates derived from N-acetyl-3-pyrrolidone and ethyl 3-oxopyrrolidine-1-carboxylate, intermediates in the synthesis of compounds (3) and (10), are discussed.