Theoretical Insight towards Mechanism, Role of NHC and DBU in the Synthesis of Substituted Quinolines

Abstract

A plausible mechanism for the conversion of aldimine to 2phenyl-4-difluoromethylquinoline catalyzed by N-heterocyclic carbene (NHC) in association with 1, 8-diazabicyclo[5.4.0]undec-7-ene (DBU) is investigated in detail by using density functional theory (DFT) method. Six significant stages are proposed to be involved in the whole catalytic cycle, starting from the generation of NHC followed by its nucleophilic interaction with the carbon atom of C═N in aldimine to generate corresponding aza-Breslow intermediate. This aza-Breslow intermediate further undergoes intramolecular umpolung addition followed by several proton transfers to regenerate the NHC along with 2phenyl-4-difluoromethylquinoline. The role of NHC in this intramolecular umpolung addition of aza-Breslow intermediate has been investigated by using conceptual DFT. Apart from NHC; the role of DBU in this catalytic cycle has also been monitored carefully. These theoretical findings are in good agreement with experimental results and also provide a deeper insight into the mechanism of NHC catalyzed synthesis of 2phenyl-4-difluoromethylquinoline.

Remote N–H activation of indole aldehydes: an investigation of the mechanism, origin of selectivities, and role of the catalyst

“…However, our recent findings show that the introduction of either Brønsted base or Brønsted acid or Brønsted base and acid together in the reaction medium can successfully lower the high activation energy barriers of proton transfer steps. [69][70][71][72] Therefore, in this studied reaction, the Brønsted base (DIEA), the in situ-generated Brønsted acid (DIEA-H2 + ), and the combined Brønsted base (DIEA) and acid (DIEA-H2 + )-assisted proton transfer mechanisms were also analysed in detail and presented in the following sections.…”

A Density Functional Theory Study on Et-BAC-Catalyzed 1,6-Conjugate Addition of p-Chlorobenzaldehyde to p-Quinone Methide for the Synthesis of α,α′-Diarylated Ketones

“…Apart from being used as ligands, NHCs are now also widely used as organocatalysts in the domain of organocatalysis . In organocatalysis, the nucleophilic attack of NHCs on the carbonyl carbon center of different organic compounds has been well accepted to activate the carbonyl carbon center and initiate a wide range of organic transformations. − Tang’s group theoretically investigated the NHC-catalyzed reaction of saturated carbonyl compounds with enones for the formation of different enantioenriched cyclopentene moieties through an inert β-C–H bond activation process (Scheme ). …”

A density functional theory investigation on bis(diethylamino)cyclopropenylidene catalyzed synthesis of 1,4‐bifunctional compounds

“…[1][2][3][4] Organocatalysts, N-heterocyclic carbenes (NHCs) have been widely used for accomplishing numerous attractive reactions via the formation of challenging carbonÀcarbon and carbonÀheteroatom bond connections. [5][6][7][8][9] In 1991, Arduengo et al [10] first isolated metal free stable NHC from thiazolium salt precursor and since then its umpolung efficiency is being continuously explored. In NHCs, the carbene carbon is located on N-heterocyclic ring scaffold with an unshared pair of electrons and an unhybridized empty p-orbital, which is primly responsible for the σ-donation and the π-acceptance capability of NHCs.…”