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 division 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.