N-Heterocyclic Carbene-Catalyzed Umpolung of Imines for the Enantioselective Synthesis of Dihydroquinoxalines

Abstract

N-heterocyclic carbene (NHC) organocatalysis is widely employed for the umpolung of aldehydes and recently to the umpolung of Michael acceptors and aldimines. Described herein is the NHC-organocatalyzed umpolung of aldimines for the enantioselective synthesis of nitrogen heterocycles. The bisimines generated from the condensation of 1,2-phenylenediamines and salicylaldehydes undergo intramolecular cyclization in the presence of a chiral NHC catalyst, resulting in the formation of dihydroquinoxalines in moderate to good yields and er values. Detailed DFT studies shed light on the role of −OH groups in stabilizing the initially generated aza-Breslow intermediates via intramolecular hydrogen bonds. Preliminary photophysical studies on the synthesized dihydroquinoxalines revealed that these molecules can be used for the sensing of various acids and bases.

Carbene‐Catalyzed Activation of Remote Nitrogen Atoms of (Benz)imidazole‐Derived Aldimines for Enantioselective Synthesis of Heterocycles

“…Our reaction is initiated via the addition of a NHC catalyst to an imine [11] derived from 2‐amino(benz)imidazole and an aldehyde to eventually form an aza ‐Breslow intermediate ( I ). Related NHC‐catalyzed formation of aza ‐Breslow intermediates for imine umpolung and asymmetric aza ‐Stetter‐type reactions have been pioneered by Douthwaite, [12a] Rovis, [12b] Lupton [12c] and Biju [12d] . In our present study, oxidation of this aza ‐Breslow intermediate leads to an electron‐deficient intermediate II in which the acidity of the remote NH from the (benz)imidazole moiety is increased.…”

Recent Advances in Enantioselective Organocatalytic Reactions Enabled by N-Heterocyclic Carbenes (NHCs) Containing Triazolium Motifs

“…If Cs2CO3 was used instead of K2CO3 the yield reported was 86% yield and 98:2 e.r, however other bases didn't work well for the reaction (Scheme 85). 179…”

Asymmetric Carbene‐Catalyzed Oxidation of Functionalized Aldimines as 1,4‐Dipoles

“…Although considerable effort has been devoted to this field, the reactions involving NHC‐activated aldimines are mainly limited to Stetter and oxidative reactions [4] . Surprisingly, only two enantioselective reactions, intramolecular cyclization and aza‐Stetter reaction based on an umpolung reaction of imines with a chiral carbene, have been successfully developed to date [4k,l] . Furthermore, in all the developed reactions the in situ carbon of the imine moiety acts as the nucleophile and reacts with other electrophilic substrates; this area of research is still in its infancy.…”