Organocatalytic Enantioselective 1,12-Addition of Alkynyl Biphenyl Quinone Methides Formed In Situ.

The chemistry of quinone methides formed in situ has been flourishing in recent years. In sharp contrast, the development and utilization of biphenyl quinone methides are rare. In this study, we achieved a remote stereocontrolled 1,12-conjugate addition of biphenyl quinone methides formed in situ for the first time. In the presence of a suitable chiral phosphoric acid, alkynyl biphenyl quinone methides were generated from α-[4-(4-hydroxyphenyl)phenyl]propargyl alcohols, followed by enantioselective 1,12-conjugate addition with indole-2-carboxylates. The strategy enabled the alcohols to serve as efficient allenylation reagents, providing practical access to a broad range of axially chiral allenes bearing a (1,1'-biphenyl)-4-ol unit, which were previously less accessible. Combined with control experiments, density functional theory calculations shed light on the reaction mechanism, indicating that enantioselectivity originates from the nucleophilic addition of alkynyl biphenyl quinone methides. Notably, not only the presence of biphenyl quinone methides as versatile intermediates was confirmed but also organocatalytic enantioselective 1,12-addition was established.

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

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,ß,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.