Symmetry in Cascade Chirality-Transfer Processes: A Catalytic Atroposelective Direct Arylation Approach to BINOL Derivatives

Herein we disclose
a scalable organocatalytic direct arylation approach for the regio-
and atroposelective synthesis of non-C2-symmetric 2,2′-dihydroxy-1,1′-binaphthalenes (BINOLs).
In the presence of catalytic amounts of axially chiral phosphoric
acids, phenols and naphthols are coupled with iminoquinones via a
cascade process that involves sequential aminal formation, sigmatropic
rearrangement, and rearomatization to afford enantiomerically enriched
BINOL derivatives in good to excellent yields. Our studies suggest
that the (local) symmetry of the initially formed aminal intermediate
has a dramatic impact on the level of enantioinduction in the final
product. Aminals with a plane of symmetry give rise to BINOL derivatives
with significantly lower enantiomeric excess than unsymmetrical ones
featuring a stereogenic center. Presumably asymmetric induction in
the sigmatropic rearrangement step is significantly more challenging
than during aminal formation. Sigmatropic rearrangement of the enantiomerically
enriched aminal and subsequent rearomatization transfers the central
chirality into axial chirality with high fidelity.