Mechanism and Stereoselectivity in an Asymmetric N-Heterocyclic Carbene-Catalyzed Carbon–Carbon Bond Activation Reaction

Abstract

The mechanism and origin of stereoinduction in a chiral N-heterocyclic carbene (NHC) catalyzed C-C bond activation of cyclobutenone has been established using B3LYP-D3 density functional theory computations. The activation of cyclobutenone as an NHC-bound vinyl enolate and subsequent reaction with the electrophilic sulfonyl imine leads to the lactam product. The most preferred stereocontrolling transition state exhibits a number of noncovalent interactions rendering additional stabilization. The computed enantio- and diastereoselectivities are in good agreement with the previous experimental observations.

Insights into the N-Heterocyclic Carbene (NHC)-Catalyzed Oxidative γ-C(sp3)–H Deprotonation of Alkylenals and Cascade [4 + 2] Cycloaddition with Alkenylisoxazoles

“…All calculations were performed by Gaussian 09 using density functional theory, which has been widely used to clarify the detailed mechanisms of the enzyme-catalyzed, organocatalytic, and transition metal-catalyzed reactions and other theoretical studies . The more successful applications can be found in the references reported by Houk, Tantillo, Sunoj, and so on. , The calculations were performed at the M06-2X level of DFT using the appropriate integral equation formalism polarizable continuum model (IEF-PCM) in a toluene or THF solvent. DFT methods, including M06-2X­(-D3), ωB97X-D, B3LYP, and B3LYP-D3BJ, incorporating seven computational levels (denoted as L1–7) were used to justify the energy viability of the stereochemical transition states involved in the stereoselectivity-determining step.…”

Recent Advances on Computational Investigations of N‐Heterocyclic Carbene Catalyzed Cycloaddition/Annulation Reactions: Mechanism and Origin of Selectivities

“…have theoretically studied mechanisms and selectivities of the NHC‐catalyzed [4+2] cycloaddition reaction of cyclobutenone 60 with imine 61 at IEFPCM THF ‐M06‐2X‐D3/6–311++G(2df, 2pd)//IEFPCM THF ‐M06‐2X/6‐31G(d, p) level . Concurrently, Sunoj's group has also investigated the mechanism and stereoselectivity of this reaction at the SMD THF ‐B3LYP‐D3/6‐31G(d, p) level . According to Wang‘s computational results, as shown in Scheme , the fundamental reaction pathway contains four steps: nucleophilic addition of NHC to cyclobutenone 60 for the formation of zwitterionic intermediate M115 , C(sp 2 )‐C(sp 3 ) bond cleavage for the formation of a dienolate intermediate M116 , [4+2] cycloaddition of M116 with isatin imine 61 to give the six‐membered ring intermediate M117 through transition state TS17 , and the elimination of NHC catalyst affording final product 62 .…”

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

“…Other theoretical research groups also contributed enormously towards the seminal development of different NHCs catalysed organic reactions by predicting the basic mechanism, chemoselectivity, enantioselectivity and importance of catalysts, counter ions and bases etc. [24][25][26][27][28][29][30][31][32] Properties and usefulness of these NHCs are now well understood, but these are in constant modification in order to improve the reactivity or efficacy of the catalyst. Umpolung efficiency of NHC is mainly governed by the generation of an acyl anion equivalent called Breslow intermediate developed by Breslow in the year 1958.…”