Regulation of Axial Chirality through Dynamic Covalent Bond Constrained Biaryls

A strategy of dynamic
covalent chemistry within constrained biaryls
was developed for the modulation of axial chirality. The ring fusion
partners of amide and aldehyde allowed the manipulation of ring/chain
equilibrium and chirality transfer within cyclic diastereomeric hemiaminal.
Dynamic covalent reactions (DCRs) with alcohols, thiols, and secondary
amines further enabled the reversal of chirality relay and thereby
regulation of axial chirality. Moreover, a combination of NMR, X-ray,
and density functional theory results shed light on the structural
basis of chirality transfer, exhibiting modest to excellent diastereoselectivity
under thermodynamic control. The critical role of the amide unit in
the modulation of axial chirality was also corroborated. Finally,
the chiroptical signal was controlled through changing solvents, DCRs,
and stimuli-responsive switching of DCRs.