Asymmetric Synthesis of Axially Chiral Benzocarbazole Derivatives Based on Catalytic Enantioselective Hydroarylation of Alkynes

Abstract

A new synthetic approach to novel axially chiral benzocarbazole derivatives based on the highly enantioselective intramolecular hydroarylation (94-96% ee) of linked alkyne-indole systems by using the prevalent chiral base catalyst, cinchonidine or cinchonine, under unprecedented transition-metal-free conditions is described. The process is considered to involve chiral base catalysis for enantioselective transformation of the alkyne part to a reaction intermediate with an axially chiral vinylidene o-quinone methide (VQM) functionality, which subsequently effects stereospecific cyclization with the tethered indole moiety.

Catalytic Asymmetric Construction of Axially Chiral Indole‐Based Frameworks: An Emerging Area

“…In 2018, the Irie group used the strategy of constructing a benzene ring to synthesize axially chiral benzocarbazole derivatives 53 via the chiral Brønsted base C13 ‐catalyzed asymmetric intramolecular hydroarylation of substrates 52 (Scheme 15 a). [37] Notably, based on their previous work on reactions involving VQM, [38] they suggested that a chiral VQM intermediate was generated in the reaction process. Moreover, in 2019, the Xu group coupled the C4 position of 5‐hydroxyindoles 39 with quinone monoimides 37 via asymmetric addition reactions in the presence of the chiral thiourea catalyst C14 (Scheme 15 b) to obtain the axially chiral C4‐arylindole frameworks 40 with excellent results [39] …”

Diversity-Oriented Enantioselective Construction of Atropisomeric Heterobiaryls and N -Aryl Indoles via Vinylidene Ortho -Quinone Methides

“…In past years, in situ generated chiral vinylidene ortho-quinone methides [35][36][37][38][39][40][41][42][43] (VQMs) have been demonstrated as a privileged intermediate for accessing diverse enantiomerically pure architectures. We speculated that its electrophilic position 4 could be utilized to undertake an intramolecular annulation with a variety of nucleophilic heteroatoms to form different types of axially chiral heterocycles.…”

Organocatalytic atroposelective construction of axially chiral N, N- and N, S-1,2-azoles through novel ring formation approach

“…Based on our previous work on VQM chemistry for heterobiaryl atropisomer synthesis 39 – 43 , we believed that VQMs could be an ideal template synthon for the collective synthesis of axially chiral 1,2-azoles. Nevertheless, reported VQMs are mostly limited to those bearing an arene ring at 5-position, so axial chiral architectures were confined to benzo- or naphtho-fused analogues 39 – 44 . To realize the synthesis of atropisomeric 1,2-azoles, we intended to design other types of VQM precursor bearing non-arene groups at 5-position.…”