Kinetic Resolution Approach to the Synthesis of C–N Axially ChiralN-Aryl Aminomaleimides via NHC-Catalyzed [3 + 3] Annulation

Abstract

Chiral NHC-catalyzed kinetic resolution of N-aryl aminomaleimides allowing the synthesis of C–N axially chiral N-aryl aminomaleimides via remote chirality control is presented. The catalytically generated α,β-unsaturated acylazoliums from 2-bromoenals underwent selective [3 + 3] annulation with one of the enantiomers of maleimide to furnish fused-dihydropyridinone (bearing axial/central chirality, up to 6:1 dr, >99:1 er) leaving the enantioenriched opposite enantiomer (up to >99:1 er). Studies on C–N bond rotation barrier and dependence on temperature are also provided.

Atroposelective Access to Dihydropyridinones with C–N Axial and Point Chirality via NHC-Catalyzed [3 + 3] Annulation

“…Recently, the [3 + 3] atroposelective annulation of enals with α-aminomaleimide for the synthesis of C–N atropisomers was reported separately by Hui and our group . Meanwhile, the kinetic resolution of aminomaleimide via NHC-catalyzed selective [3 + 3] annulation was reported by Biju and co-workers . All of the above-mentioned reports successfully superposition a point chiral element with a C–N axial backbone via NHC-catalyzed atroposelective transformations.…”

Carbene-catalyzed kinetic resolution of bispirooxindoles: selective lactam amidation and access to challenging chiral scaffolds

“…Kinetic resolution (KR) is one of the most convenient and reasonable methods for preparing pure chiral monomeric compounds from racemic mixtures. [1][2][3][4] Importantly, strategies involving N-heterocyclic carbene (NHC)-catalyzed KR have recently been demonstrated to be promising vehicles for the fabrication of chiral cyclic amines, esters, alcohols, and sulfoximines as well as phenols, as they effectively minimize the possibility of competitive racemic background reactions encountered with the application of other non-selective reagents such as acyl chlorides and anhydrides (Fig. 1a).…”

N‐Heterocyclic carbene‐catalyzed Atroposelective Annulation for Access to Pyrrolo[3,4‐b]pyridines Derivatives with C−N Axial Chirality

“…Very recently, NHC catalyzed atroposelective synthesis of C−N atropoisomers were reported by Wang, Biju and Chi respectively [6] . Very recently, the kinetic resolution of N‐aryl aminomaleimides for the construction of C−N axially chiral product was reported by Biju's group [7] . Herein, we reported an NHC catalytic approach for the highly atroposelective access to various pyrrolo[3,4‐ b ]pyridines derivatives with C−N axial chirality.…”

“…[6] Very recently, the kinetic resolution of N-aryl aminomaleimides for the construction of CÀ N axially chiral product was reported by Biju's group. [7] Herein, we reported an NHC catalytic approach for the highly atroposelective access to various pyrrolo [3,4-b]pyridines derivatives with CÀ N axial chirality. α-Aminomaleimides were proved could be used as an excellent nucleophile in various nucleophilic addition reactions.…”