Asymmetric Catalytic 1,6-Conjugate Addition/Aromatization of para-Quinone Methides: Enantioselective Introduction of Functionalized Diarylmethine Stereogenic Centers

摘要

para-Quinone methides [p-QMs; Eq. (1)],which are structurally characterized by the unique assembly of carbonyl and olefinic moieties, and chemically defined as neutral and zwitterionic resonance entities, have been already known for more than one century in organic chemistry. In nature, p-QM units exist in a variety of natural products such as fungal metabolites, terpenes, and plant pigments. As a result of the intrinsic electrophilic reactivity of p-QMs, highly reactive transient p-QM species generated in situ are implicated in many chemical, medicinal, and biological processes such as lignin biosynthesis, enzyme inhibition, and DNA alkylation and cross-linking. Synthetically, ortho-quinone methides (o-QMs), a structural isomer of p-QMs, have been extensively studied for the development of asymmetric methodologies such as 1,4-conjugate addition, [4+2]-cycloaddition, and 6π electrocyclization. But surprisingly, few enantioselective additions of p-QMs have been documented, especially in a catalytic asymmetric fashion. Therefore, the development of an effective catalytic enantioselective addition of p-QMs remains an important challenge in modern organic svn thesis.