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

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.