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

Five A-ring analogs of duocarmycin SA 9a-e were synthesized in racemic form modifying our second synthetic route toward duocarmycin SA, The problem en countered at the crucial phenol forming step to secure 17a, b from 16a, b u nder 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 carbona te (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.