Organocatalytic Enantioselective 1,8-Addition for the Synthesis of Chiral Tetraarylmethanes from 2-Naphthol/Naphthalen-2-amine-Based Tertiary Alcohols.

Abstract

Catalytic enantioselective construction of optically active tetraarylmethanes remains a challenging issue in the field of asymmetric synthesis because of the overwhelming steric hindrance and formidable stereocontrol that existed in construction of the all-aryl-substituted quaternary carbon stereocenter. Here, we reported an organocatalytic asymmetric synthesis of chiral tetraarylmethanes from racemic tertiary alcohols. With the aid of a chiral phosphoric acid catalyst, 6-methylenenaphthalen-2(6H)-ones were generated in situ from 6-(hydroxydiarylmethyl)naphthalen-2-ols, followed by stereoselective 1,8-conjugate addition to afford the corresponding tetraarylmethanes in high to excellent yields with high enantioselectivities. Furthermore, the scope of tertiary alcohols has been successfully enlarged to 6-(hydroxydiphenylmethyl)naphthalen-2-amines. Notably, it is the first time to use 2-naphthol/naphthalen-2-amine unit as the auxiliary group to in situ generate α,β,γ,δ,ε,ζ-conjugate systems, which have been successfully involved in organocatalytic remote stereocontrolled 1,8-conjugate addition reactions. Particularly, organocatalytic stereoconvergent formal nucleophilic substitution reaction of triarylmethanols has been achieved for the asymmetric construction of chiral tetraarylmethanes. In addition, DFT calculations have been applied to provide guidance for the design of additional tertiary alcohols and understand the origin of stereoselectivity.