The effect of the N-mesityl group in NHC-catalyzed reactions

Abstract

The majority of N-heterocyclic carbene catalyzed reactions of α-functionalized aldehydes, including annulations, oxidations, and redox reactions, occur more rapidly with N-mesityl substituted NHCs. In many cases, no reaction occurs with NHCs lacking ortho-substituted aromatics. By careful competition studies, catalyst analogue synthesis, mechanistic investigations, and consideration of the elementary steps in NHC-catalyzed reactions of enals, we have determined that the effect of the N-mesityl group is to render the initial addition of the NHC to the aldehyde irreversible, thereby accelerating the formation of the Breslow intermediate. These studies rationalize the experimentally observed catalyst preference for all classes of NHC-catalyzed reactions of aldehydes and provide a roadmap for catalyst selection and design.

Characterization of the Key Intermediates of Carbene‐Catalyzed Umpolung by NMR Spectroscopy and X‐Ray Diffraction: Breslow Intermediates, Homoenolates, and Azolium Enolates

“…[29] Taken together, these observations nicely parallel conclusions from recent studies by Bode et al on N-mesityl triazolylidenes, namely that the formation of the diamino dienol from a-methyl E-cinnamic aldehyde (2 h) is reversible, whereas the analogous transformation of E-cinnamic aldehyde (2 g) is irreversible. [30] In summary, the selective generation and characterization [31] of diamino enols, diamino dienols, azolium enolates, and an azolium enol reported herein for the first time puts the mechanistic analysis of NHC-catalyzed a 1 -d 1 and a 3 -d 3 umpolung on a solid structural basis. Thus, a number of hitherto postulated reaction intermediates were prepared and characterized.…”

Proton Transfer Reactions of Triazol-3-ylidenes: Kinetic Acidities and Carbon Acid pKa Values for Twenty Triazolium Salts in Aqueous Solution

“…27 We have measured a suggested that the more electron withdrawing N-pentafluorophenyl triazolium salts are more acidic than the corresponding N-mesityl salts. 45 An even smaller N-aryl substituent effect on k DO is observed across the morpholinyl series of triazolium salts 14c-f in water.…”

“…Mahatthananchai have shown that N-pentafluorophenyl triazolium salts are more acidic than the corresponding N-mesityl salts, 45 implicating that less of the corresponding active NHC is likely to be generated under typical reaction conditions. Further experimentation led them to elegantly ascribe the N-mesityl effect to irreversible initial addition of the NHC to the enal.…”

Ferrocene‐Based Planar Chiral Imidazopyridinium Salts for Catalysis

“…Catalysts 4b and 4d afforded only 20 %c onversion;t his insufficient reactivity may be due to the lack of ortho substituents on the pendant aromatic ring, which is considered to be crucial for catalyst performance. [19] Catalyst 4c provided the highest levels of enantioselectivity (85:15 e.r. for the cis diastereomer), but without any diastereoselectivity (1:1 d.r.).…”