One-Step Construction of Atropisomers Bearing 1,5-Central and Axial Chirality via Catalytic Diastereo- and Atroposelective Remote Desymmetrizing Alkynylation

Abstract

Catalytic asymmetric construction of atropisomers with multiple stereogenic elements has recently become an emerging area. However, general methods that produced atropisomers bearing remote 1,5-axial and central chirality efficiently and stereoselectively are scarce yet highly challenging. We herein report a catalytic diastereo- and atroposelective remote desymmetrizing alkynylation of axially prochiral dialkynes with ortho-quinone methides (o-QMs), furnishing atropisomers bearing 1,5-remote centrally and axially stereogenic elements. The remote control of prochiral axis far from the reaction site could be simultaneously achieved during the stereoselective C(sp³)–C(sp) bond-forming process to generate a stereogenic center. In addition, a kinetic resolution of axially racemic alkynes via diastereo- and atroposelective remote alkynylation with o-QMs has been developed, further enriching structural diversity of atropisomers bearing 1,5-central and axial chirality. The present method expands the chemical space of atropisomeric molecules bearing multiple chiral elements by facile downstream diversification of C–C triple bonds. Finally, the alkynylation of o-QMs can also be applied for the construction of chiral motifs bearing 1,9- and 1,10-stereogenic centers.