Enantioselective synthesis of ring-constrained biaryls via a twist-expand-seal strategy

Ring-constrained biaryls possess unique axial chirality, but methods to synthesize them with adjustable ring sizes remain limited. We report a “twist-expand-seal” strategy for preparing a unique class of cyclic biaryls that exhibit axial chirality and conformational constraint, with tunable ring sizes. This method enables the streamlined synthesis of 9- to 14-membered cyclic biaryls, achieving yields of up to 99% and enantioselectivities of up to 99% ee (49 examples). This approach begins with enantioselective ring-opening of a “flat” biaryl-embedded lactam mediated by a bifunctional chiral N-heterocyclic carbene (NHC) catalyst (twist). Chain expansion is achieved via introducing alcohols of varying chain lengths (expand), and the final ring closure is accomplished through diverse C–C or C–N bond-forming reactions (seal). Scalable synthesis and subsequent ring transformations are readily achieved. This work expands the chemical space of axial chirality by enabling the versatile synthesis of diverse biaryl-bridged ring scaffolds. The authors report a “twist-expand-seal” strategy for synthesizing a unique class of cyclic biaryls that exhibit axial chirality and conformational constraint, with adjustable ring sizes.