Grinding-Assisted Organocatalytic Asymmetric Synthesis of Eight-Membered Bridged Biaryls

Herein, we disclose a grinding-enabled, enantioselective organocatalytic approach to eight-membered carbocyclic biaryl-bridged frameworks under solvent-free mechanochemical conditions. By employing a hydrogen-bonding organocatalyst, a domino Michael-Henry sequence between indole- or benzothiophene-derived biaryl substrates and β-dicarbonyl compounds proceeds efficiently in a mixer mill, without external solvents or additives. This operationally simple protocol rapidly delivers a rare class of eight-membered bridged biaryls featuring multiple stereocenters and a chiral axis in high yields and excellent enantioselectivities.