Developing Biarylhemiboronic Esters for Biaryl Atropisomer Synthesis via Dynamic Kinetic Atroposelective Suzuki–Miyaura Cross-Coupling

Abstract

We herein introduce biarylhemiboronic esters as a new type of bridged biaryl reagent for asymmetric synthesis of axially chiral biaryl structures, and the palladium-catalyzed asymmetric Suzuki−Miyaura cross-coupling of biarylhemiboronic esters is developed. This dynamic kinetic atroposelective coupling reaction exhibits high enantioselectivity, good functional group tolerance, and a broad substrate scope. The synthetic application of the current method was demonstrated by transformations of the product and a programmed synthesis of chiral polyarene. Preliminary mechanistic studies suggested that the reaction proceeded via an enantio-determining dynamic kinetic atroposelective transmetalation step.

Development of Configurationally Labile Biaryl Reagents for Atropisomer Synthesis

“…Recently, Dou and co-workers developed biarylhemiboronic esters as novel configurationally labile biaryl reagents for atropisomer synthesis (Scheme 18a). [69] The boron-containing bridged biaryls served as nucleophilic biaryl reagent as well as exhibited merits of both torsional strain-independent reactivity and versatile transformations. The low atropisomerization barrier indicated the fast interconversion between two configurations of hemiboronic esters, laying the foundation for the dynamic kinetic asymmetric transformations.…”