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

Abstract

An ew mode of carbene-catalyzed heteroatom activation and asymmetric reactions is disclosed. The reaction starts with addition of acarbene catalyst to a(benz)imidazolederived aldimine substrate.S ubsequent oxidation and proton transfer lead to the formation of acatalyst-bound triaza-diene as the key intermediate,i nw hich the nitrogen atom at as ite remote to the catalyst-substrate bond is activated. This unusual triaza-diene intermediate then undergoes highly enantioselective reactions with activated ketones through ac oncerted asynchronous pathway,a ss upported by mechanistic studies and preliminary density function theory calculation.

Atroposelective Access to 1,3‐Oxazepine‐Containing Bridged Biaryls via Carbene‐Catalyzed Desymmetrization of Imines

“…Related carbene‐catalyzed formation of aza ‐Breslow intermediates for imine umpolung and asymmetric reactions have been reported by Lupton, [15a] Biju [15b] and our group [15c–d] . Besides, the carbene‐catalyzed oxidative imine umpolung for enantioselective [4+2] cycloaddition has been achieved by Fu [16a] and us [16b] in the mean time. This work represents the first success in developing oxidative imine umpolung to access the axially chiral compounds.…”

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

“…Recently, Yang et al disclosed an efficient method that involves carbene-catalyzed remote activation of a heteroatom and asymmetric reactions. 185 The NHC organocatalytic reaction was investigated using aldimine 229 and isatinbased ketone 175 (Scheme 90). In the presence of tetra-butyldiphenylquinone (DQ) as the oxidant and N,N-diisopropylethylamine (DIPEA) as the base, the application of NHC•HBF 4 catalyst AM 49 led to a 98% yield of product 230 with an enantiomeric ratio of up to 98:2.…”

Exploring Molecular Complexity by N‐Heterocyclic Carbene Organocatalysis: New Activation and Reaction Diversity

“…The reaction of (benz)imidazolederived aldimine 58 with electron‐deficient ketone 51 such as isatin provided novel spiro‐bicyclic products 59 in high yields and excellent enantioselectivities (Scheme 18). [32] Briefly, the reaction occurred through the initial addition of the NHC catalyst to the imine 58 , followed by the generation of aza‐Breslow intermediate I after proton transfer process. In the presence of the DQ oxidant, the aza‐Breslow species could be oxidized to the electron‐deficient intermediate II that enhances the acidity of the remote NH.…”