Asymmetric Synthesis of Atropisomers Featuring an Aza-Axis via N-Heterocyclic Carbene Catalysis.

Abstract

The research of atropisomerism containing aza axes (such as C─N, N─N, C─O, and C─B) in synthetic chemistry has drawn considerable attention in the past few years, primarily due to its importance to natural products total synthesis, pharmaceuticals, and materials science. In contrast to the well-established field of C─C atropisomers, the catalytic asymmetric construction of aza-axial chirality was largely overlooked for a long time until the seminal reports by Taguchi and Curran in the early 2000s. This review mainly summarizes the progress in N-heterocyclic carbene-mediated atroposelective construction of aza-axial chiral atropisomers, covering strategies including kinetic resolution (KR), dynamic KR, desymmetrization, de novo annulation, and direct atroposelective N-acylation. Despite these achievements, the asymmetric synthesis of aza-axial chirality remains far less developed than that of C─C atropisomers, owing to the difficulty in controlling enantioselectivity. Exploration of efficient and novel methods for constructing aza-axial chiral molecules is highly desirable.