Enantioselective Synthesis of Atropisomers by Oxidative Aromatization with Central-to-Axial Conversion of Chirality

Abstract

Atropisomers are fascinating objects of study by themselves for chemists but also find applications in various sub-fields of applied chemistry. Obtaining them in enantiopure form is far from being a solved challenge, and the past decades has seen a surge of methodological developments in that direction. Among these strategies, oxidative aromatization with central-to-axial conversion of chirality has gained increasing popularity. It consists of the oxidation of a cyclic non-aromatic precursors into the corresponding aromatic atropisomers. This review proposes a critical analysis of this research field by delineating it and discussing its historical background and its present state of the art to draw potential future development directions.

Enantioselective Synthesis of Heteroatom‐Linked Non‐Biaryl Atropisomers

“…Liu and colleagues' method [26] distinguishes itself from previous examples by facilitating direct CÀ N bond formation through a domino process via an enantioselective aza-Michael addition leading to centrally chiral intermediates 11 with a six-membered ring intramolecular NÀ H•••O hydrogen bond interaction (Scheme 4). Subsequent tautomerization with central-to-axial chirality conversion [27] and in situ oxidation of the resulting axially chiral hydroquinones 12 render a new family of N-aryl quinone atropisomers 10. This direct C4 CPA-catalyzed atroposelective coupling between quinone esters 8 and hindered anilines 9 proceeded in good yields and enantioselectivities (up to 88 % yield and 99 % ee, Scheme 4).…”

Transition-metal-catalyzed atroposelective synthesis of axially chiral styrenes

“…With the mechanism revealed by Paton in 2018, 47 organocatalyzed [1,3]-H transfer has evolved as a powerful method in the stereospecific isomerization of allylic compounds. 48 Stimulated by the organocatalysis approaches, several works about iridium( i )-catalyzed atroposelective synthesis of axially chiral styrenes have been reported. A tertiary carbon stereocenter precursor is formed via asymmetric allylation, followed by an enantiospecific [1,3]-proton transfer or [1,3]-hydride transfer to achieve chirality transfer from central to axial.…”

Asymmetric Synthesis of Axially Chiral Molecules via Organocatalytic Cycloaddition and Cyclization Reactions

“…As a result, its asymmetric synthesis has become a hot topic in the field of organic synthesis [25]. The existing synthetic methods mainly include coupling, aromatic ring construction, chiral separation/desymmetrization and chiral transformation [26][27][28][29][30]. Cycloaddition and cyclization are common methods in the ring construction, which are efficient and environmentally friendly synthetic methods [31,32].…”