Access to the Enantiopure Axially Chiral Cyclophane IsoplagiochinD through Atropo-diastereoselective Heck Coupling

摘要

Macrocyclization is typically the key step in the syntheses of cyclophane-type natural products. Considering cyclophanes with axially chiral biaryl moieties, the control of atroposelectivity is essential with biological activity and is synthetically challenging. We report an atroposelective approach involving Heck cyclization, which for the first time enables the total synthesis of an enantiopure macrocyclic bis(bibenzyl), namely isoplagiochinD. An enantiopure sulfinyl auxiliary in the ortho position of a biaryl axis (still flexible) was used to induce an atropo-diastereoselective Heck coupling (up to 98% de). The traceless character of the sulfinyl auxiliary enables the introduction of a hydroxy group to give the target molecule with 98% ee as well.