Total Synthesis of Marinoquinoline A Using a Palladium(0)-Catalyzed Ullmann Cross-Coupling Reaction

Abstract

The title natural product, 1, has been synthesized. The pivotal steps are a Pd0-catalyzed Ullmann cross-coupling of the 3-iodopyrrole-2-carboxaldehyde 13 with o-bromonitrobenzene (14), conversion of the resulting 3-arylpyrrole 15 into methylketone 17, and reductive cyclization of 17 by using magnesium in methanol to give target 1 in 85% yield. Coming together: A convergent synthesis of the biologically active alkaloid marinoquinolineA, which embodies a 3H-pyrrolo[2,3-c]quinolone ring system, has been developed. Key steps include a Pd0-catalyzed Ullmann cross-coupling of a 3-iodopyrrole-2-carboxaldehyde with o-bromonitrobenzene, and a reductive cyclization with magnesium in methanol to complete the synthesis of the quinoline substructure and, thereby, the natural product. Ts=4-toluenesulfonyl. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.