Highly Enantioselective Synthesis of beta-Heteroaryl-Substituted Dihydrochalcones Through Friedel-Crafts Alkylation of Indoles and Pyrrole

A highly enantioselective Friedel-Crafts (F-C) alkylation of indoles and pyrrole with chalcone derivatives catalyzed by a chiral N,N'-dioxide-Sc(OTf)(3) complex has been developed that tolerates a wide range of substrates. The reaction proceeds in moderate to excellent yields and high enantioselectivities (85-92% enantiomeric excess) using 2mol% (for indole) or 0.5 mol% (for pyrrole) catalyst loading, which showed the potential value of the catalyst system. Meanwhile, a strong positive nonlinear effect was observed. On the basis of the experimental results and previous reports, a possible working model is proposed to explain the origin of the activation and asymmetric induction.