Organocatalytic Atroposelective Construction of Axially Chiral N-Aryl Benzimidazoles Involving Carbon–Carbon Bond Cleavage

Abstract

Full experiments and characterization data including 1 H and 13 C NMR spectra and HPLC for the synthesized products ((S)-3a−3aj and (S)-4−7) (PDF)Accession Codes CCDC 1963357 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk

Asymmetric Synthesis of Axially Chiral C−N Atropisomers

“…An alternative methodology for the atroposelective synthesis of axially chiral N ‐aryl benzimidazoles has recently been reported by Fu and co‐workers [75] . In this approach, the reaction of N ‐(aryl)benzene‐1,2‐diamines 144 with dicarbonyl compounds 145 or 146 proceeds with C−C bond cleavage of the latter, yielding products 147 and 148 , respectively.…”

Enantioselective Synthesis of Axially Chiral Benzimidazoles ­Bearing a C–N axis via Pd-Catalyzed Buchwald–Hartwig ­Amination

“…16 However, few efforts are devoted to the asymmetric synthesis of axial C-N benzimidazole atropisomers due to its decreased configurational stability. [17][18][19] Scheme 1 Representative molecules containing C-N benzimidazole atropisomers…”

“…16 However, few efforts are devoted to the asymmetric synthesis of axial C-N benzimidazole atropisomers due to its decreased configurational stability. [17][18][19] In 2018, Toste and Miller pioneered the asymmetric synthesis of C-N benzimidazole atropisomers through intramolecular cyclodehydration of ortho-substituted anilines (Scheme 1). 17 The utility of hydrogen-bond-donor catalyst, such as phosphothreonine-embedded peptidic phosphoric acids ('pThr-type' CPA) and C 2 -symmetric chiral phosphoric acids ('C 2 -type' CPA), helped to furnish the construction of benzimidazole bearing a C-N axis.…”

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

“…In 2020, Fu and co-workers described the chiral phosphoric acid-catalyzed atroposelective construction of axially chiral N -arylbenzimidazoles involving a carbon–carbon bond cleavage under optimal reaction conditions. In the presence of CPA 2 , N 1 -(aryl)benzene-1,2-diamines 66 were used in the reaction with multicarbonyl compounds 67 and 68 and afforded the corresponding products, axially chiral N -arylbenzimidazoles 69 and 70 in high yields (up to 89%) with excellent enantioselectivity (up to 98% ee, Scheme 22 ) [ 78 ]. The primary amino group in the N 1 -(aryl)benzene-1,2-diamines reacts with the carbonyl group in 67 to give imine intermediate I-15 mediated by the chiral phosphoric acid.…”