Studies on Chromium(0)-Promoted Higher-Order Cycloaddition-Based Benzannulation. Total Synthesis of (+)-Estradiol

Abstract

A benzannulation sequence featuring [6π + 4π] cycloaddition of (η 6 -thiepin 1,1-dioxide)tricarbonylchromium(0) complexes with highly substituted dienes followed by Ramberg−Bäcklund rearrangement has been developed. Enantiomerically pure (+)-estradiol (estra-1,3,5(10)-triene-3,17β-diol) has been synthesized by employing a higher-order cycloaddition between an appropriately substituted thiepin dioxide chromium(0) complex and a diene partner derived from an enantiomerically pure indandione precursor as the key ring construction event. Subsequent Ramberg−Bäcklund rearrangement of this cycloadduct and routine functional group interchanges afforded the steroid target.