N-Heterocyclic Carbene Catalysis Exploiting Oxidative Imine Umpolung for the Generation of Imidoyl Azoliums

Abstract

Although NHC-catalyzed umpolung of imines are known, the related reactions under oxidative conditions are limited. Described herein is the two-step process involving the initial formation of aldimines from the corresponding aldehydes and 2-amino benzyl alcohols followed by NHC-catalyzed cyclization proceeding via the imidoyl azoliums under oxidative conditions. The reaction allowed the synthesis of trifluoromethylated 3,1-benzoxazines in good yields and broad scope. The role of NHC in the intramolecular cyclization and preliminary mechanistic experiments are also provided.

Recent Advances in N‐Heterocyclic Carbene Catalyzed Oxidative Cyclization for the Formation of Heterocycles

“…Extending the strategy, Biju and co-workers employed aldimines 207 derived from (2-aminophenyl)-2,2,2-trifluoroethanol and its derivatives 205 with aromatic aldehydes 191 for the synthesis of 3,1-benzoxazines 208 (Scheme 56). [82] The mechanism of the reaction was similar to the one discussed above and it was found that the initially generated aldimines go through an intra-molecular cyclization under oxidative NHC catalysis through the imidoyl azolium intermediates. The synthetic utility of this strategy was utilized for the synthesis of Efavirenz (Possessing anti HIV activity), employing this one-pot generation of 3,1-benzoxazines.…”

“…Intramolecular cyclization of aldimines 201 , synthesized from 2‐aminophenols and aromatic aldehydes under NHC catalysis resulted in the formation of 2‐aryl benzoxazoles 202 (Scheme 55). [82] Formation of aza‐breslow intermediate 203 obtained from aldimine and NHC was the key step of the reaction which on oxidation led to the generation of imidoyl azoliums 204 and further intramolecular cyclization gave the product in good yields.…”

p‐TSA‐Mediated Four‐Component Reaction: One‐Step Access to Mesoionic 1H‐Imidazol‐3‐ium‐4‐olates, Direct NHC Precursors

“…Excellent reviews [26,27] on NHCs emphasized three major applications of these species, such as their coordination to transition metals, [28] coordination to pblock elements, [29] and as organocatalysts. [30][31][32][33] NHCs have been reported several times, e. g., [24,[34][35][36][37][38][39] and anionic NHCs appear less frequently in the literature. [23,[40][41][42]…”

Unexpected Annulation between 2-Aminobenzyl Alcohols and Benzaldehydes in the Presence of DMSO: Regioselective Synthesis of Substituted Quinolines

“…Notably, Biju and co-workers developed N-heterocyclic carbene (NHC) and p-toluenesulfonic acid (PTSA) catalyzed two-step synthesis of trifluoromethylated 3,1-benzoxazines through an annulation reaction of (2aminophenyl)-2,2,2-trifluoroethanol and aromatic aldehydes using toluene as solvent (Scheme 1b). 7 In their works, 2aminobenzyl alcohols provided three carbon atoms, one nitrogen atom, and one oxygen atom to the 3,1-benzoxazine framework. Aromatic aldehydes furnished one carbon atom to the C2 position of trifluoromethylated 3,1-benzoxazines.…”