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.