Enantioselective syntheses of atropisomers featuring a five-membered ring

Abstract

Atropisomerism is a fundamental property of molecules featuring a hindered rotation around a chemical bond. If six-membered ring biaryl or heterobiaryl atropisomers are the most popular ones, the focus of this feature article will be put on less common and more challenging five-membered ring containing atropisomers displaying either a stereogenic C-N or C-C bond. After an historical background, a description of the latest flourishing enantioselective strategies for the construction of this attractive family of atropisomers will be presented.

Conversion of two stereocenters to one or two chiral axes: atroposelective synthesis of 2,3-diarylbenzoindoles

“…N-Heterocyclic atropisomers are of particular interest for chemists due to the presence of a nitrogen atom that would exert steric and electronic effects during their bonding to substrates or metals; this makes these atropisomers ideal candidates for application as catalysts or ligands 3,15. Compared to the well-documented preparation of six-six-membered biaryl atropisomers, the construction of five-six-membered species is still a challenge in modern asymmetric synthesis 16. This is due to the fact that the increased distance between ortho -substituents adjacent to the axis dramatically reduces the conformational stability; this makes racemization easy to take place.…”

Organocatalytic Atroposelective Intramolecular [4+2] Cycloaddition: Synthesis of Axially Chiral Heterobiaryls

“…[7] In sharp contrast, the enantioselective construction of atropisomeric heteroaryl structures still constitutes adaunting challenge of modern organic synthesis. [8] A fewo utstanding cases of the enantioselective synthesis of atropisomeric heteroaryl structures have been reported (Scheme 1a). [9] However,m ost of the accessible chiral heteroaryl backbones are restricted to Nheteroatropisomers.…”

A Bird's Eye View of Atropisomers Featuring a Five‐Membered Ring

“…This more appealing but highly challenging alternative emerged at the beginning of the last decade and has attracted strong recent interest, notably with the development of organocatalytic transformations. It includes complementary strategies based on both stoichiometric and catalytic enantioselective methods, starting variously with simple achiral, prochiral, or racemic precursors, which have been comprehensively reviewed very recently . Therefore, the next section offers an update of this growing field, presenting the small number of very recent and elegant approaches that allow direct enantioselective access to axially chiral five‐membered atropisomers.…”