Atroposelective synthesis of sterically hindered stereochemically complex BINOL derivatives via central-to-axial chirality induction

Abstract

A sequential strategy is proposed for the atroposelective construction of new families of sterically hindered BINOL derivatives bearing multiple stereogenic elements and featuring up to four stereogenic centers. The sequence begins with an organocatalyzed regio- and enantioselective mono-dihydrobenzofurannulation of commercially available 2,7-dihydroxynaphthalene establishing two stereogenic carbon atoms, followed by highly atroposelective copper-catalyzed aerobic oxidative homo- or cross-couplings fixing the axial chirality thanks to a nearly perfect induction of chirality. In addition, the resulting BINOL derivatives serve as promising precursors for the synthesis of either complex spiroheterocycles by axial-to-central conversion of chirality, heterohelicene-like molecules by axial-to-helical conversion of chirality, or an atropisomeric naphtho[2,1-b]furan scaffold via 1,2-aryl migration, further underscoring the potential of this new atroposelective strategy based on a practical central-to-axial chirality induction.