Preparation of benzene, furan, and thiophene analogs of duocarmycin SA employing a newly-devised phenol-forming reaction

Abstract

Five A-ring analogs of duocarmycin SA 9a - e were synthesized in racemic form modifying our second synthetic route toward duocarmycin SA. The problem encountered at the crucial phenol forming step to secure 17a, b from 16a, b under the conventionally used Kuwajima conditions was overcome by devising a more convenient method: simple heating of 16a - c in benzene in the presence of bis(triphenylphosphine)palladium(II) chloride (10 mol%), cesium carbonate (3 eq), and triphenylphosphine (0.3 eq) gave 17a - c in high yields of 86 - 91%. The intermediates 17a - e were readily led to the A-ring analogs (±)-9a - e almost according to the reported route.