Continuous‐Flow N‐Heterocyclic Carbene Generation and Organocatalysis

Two methods were assessed for the generation of common N‐heterocyclic carbenes (NHCs) from stable imidazol(in)ium precursors using convenient and straightforward continuous‐flow setups with either a heterogeneous inorganic base (Cs₂CO₃ or K₃PO₄) or a homogeneous organic base (KN(SiMe₃)₂). In‐line quenching with carbon disulfide revealed that the homogeneous strategy was most efficient for the preparation of a small library of NHCs. The generation of free nucleophilic carbenes was next telescoped with two benchmark NHC‐catalyzed reactions; namely, the transesterification of vinyl acetate with benzyl alcohol and the amidation of N‐Boc‐glycine methyl ester with ethanolamine. Both organocatalytic transformations proceeded with total conversion and excellent yields were achieved after extraction, showcasing the first examples of continuous‐flow organocatalysis with NHCs.     

Proton‐Transfer Polymerization (HTP): Converting Methacrylates to Polyesters by an N‐Heterocyclic Carbene

A new polymerization termed proton (H)‐transfer polymerization (HTP) has been developed to convert dimethacrylates to unsaturated polyesters. HTP is catalyzed by a selective N‐heterocyclic carbene capable of promoting intermolecular Umpolung condensation through proton transfer and proceeds through the step‐growth propagation cycles via enamine intermediates. The role of the added suitable phenol, which is critical for achieving an effective HTP, is twofold: shutting down the radically induced chain‐growth addition polymerization under HTP conditions (typically at 80–120 °C) and facilitating proton transfer after each monomer enchainment. The resulting unsaturated polyesters have a high thermal stability and can be readily cross‐linked to robust polyester materials.     

Enantioselective Synthesis of Tertiary Propargylic Alcohols under N‐Heterocyclic Carbene Catalysis

A straightforward procedure to carry out the enantioselective benzoin reaction between aldehydes and ynones by employing a chiral N‐heterocyclic carbene (NHC) as catalyst was developed. Under the optimized reaction conditions, these ynones undergo a clean and selective 1,2‐addition with the catalytically generated Breslow intermediate, not observing any byproduct arising from competitive Stetter‐type reactivity. This procedure allows the preparation of tertiary alkynyl carbinols as highly enantioenriched materials, which have the remarkable potential to be used as chiral building blocks in organic synthesis.     

Cooperative Catalysis and Activation with N‐Heterocyclic Carbenes

N‐Heterocyclic carbene (NHC) catalysis has emerged as a powerful stratagem in organic synthesis to construct complex molecules primarily by polarity reversal (umpolung) approaches. These unique Lewis bases have been used to generate acyl anions, enolates, and homoenolates in catalytic fashion. Recently, a new strategy has emerged that dramatically expands the synthetic utility of carbene catalysis by leveraging additional activation modes: cooperative catalysis. The careful selection and balance of cocatalysts have led to enhanced reactivity, increased yields, and improved stereoselectivity. In certain cases, these catalytic additives have changed the regioselectivity or diastereoselectivity. This Minireview highlights new advances in NHC cooperative catalysis and surveys the evolution of this field.     

N‐Heterocyclic Carbene Catalyzed Photoenolization/Diels–Alder Reaction of Acid Fluorides

The combination of light activation and N‐heterocyclic carbene (NHC) organocatalysis has enabled the use of acid fluorides as substrates in a UVA‐light‐mediated photochemical transformation previously observed only with aromatic aldehydes and ketones. Stoichiometric studies and TD‐DFT calculations support a mechanism involving the photoactivation of an ortho‐toluoyl azolium intermediate, which exhibits “ketone‐like” photochemical reactivity under UVA irradiation. Using this photo‐NHC catalysis approach, a novel photoenolization/Diels–Alder (PEDA) process was developed that leads to diverse isochroman‐1‐one derivatives.     

A Facile Route to Backbone‐Tethered N‐Heterocyclic Carbene (NHC) Ligands via NHC to aNHC Rearrangement in NHC Silicon Halide Adducts

The reaction of 1,3‐diisopropylimidazolin‐2‐ylidene (iPr₂Im) with diphenyldichlorosilane (Ph₂SiCl₂) leads to the adduct (iPr₂Im)SiCl₂Ph₂ 1 . Prolonged heating of isolated 1 at 66 °C in THF affords the backbone‐tethered bis(imidazolium) salt [(^aHiPr₂Im)₂SiPh₂]²⁺ 2 Cl^? 2 (“^a” denotes “abnormal” coordination of the NHC), which can be synthesized in high yields in one step starting from two equivalents of iPr₂Im and Ph₂SiCl₂. Imidazolium salt 2 can be deprotonated in THF at room temperature using sodium hydride as a base and catalytic amounts of sodium tert‐butoxide to give the stable N‐heterocyclic dicarbene (^aiPr₂Im)₂SiPh₂ 3 , in which two NHCs are backbone‐tethered with a SiPh₂ group. This easy‐to‐synthesize dicarbene 3 can be used as a novel ligand type in transition metal chemistry for the preparation of dinuclear NHC complexes, as exemplified by the synthesis of the homodinuclear copper(I) complex [{^a(ClCu?iPr₂Im)}₂SiPh₂] 4 .     

N‐Heterocyclic Carbene Catalyzed γ‐Dihalomethylenation of Enals by Single‐Electron Transfer

An N‐heterocyclic carbene (NHC) catalyzed dihalomethylenation of enals is described. It is a rare example of merging NHC catalysis with single‐electron chemistry, a challenging topic with limited previous success. The versatile carbon‐centered trihalomethyl radicals have been demonstrated, for the first time, to be compatible with an NHC‐bound intermediate, thus leading to efficient and regioselective intermolecular C?C bond formation. The mild process provides straightforward access to unsaturated δ,δ‐dihalo esters.     

N‐Heterocyclic Carbene Catalysis via Azolium Dienolates: An Efficient Strategy for Remote Enantioselective Functionalizations

N‐heterocyclic carbene (NHC) catalysis has emerged as a powerful strategy in organic synthesis. In recent years a number of reviews have been published on NHC‐catalyzed transformations involving Breslow intermediates, acyl azoliums, α,β‐unsaturated acyl azoliums, homoenolate equivalents, and azolium enolates. However, the azolium dienolate intermediates generated by NHCs have been employed in asymmetric synthesis only very recently, especially in cycloadditions dealing with remote functionalization. This Minireview highlights all the developments and the new advances in NHC‐catalyzed asymmetric cycloaddition reactions involving azolium dienolate intermediates.     

Comparative Theoretical Study of N‐Heterocyclic Carbenes and Other Ligands Bound to AuI

The bonding strength of N‐heterocyclic carbene (NHC) ligands to a neutral AuCl test moiety are compared to that of several phosphanes and other ligands. Of the ligands studied, the NHCs clearly form the strongest bonds to AuCl. A simplified triangular CN₂ model is also introduced for the NHCs.     

N‐Heterocyclic Carbene Stabilized Boryl Radicals

The reaction of the 2‐(trimethylsilyl)imidazolium triflate 9 with diarylboron halides (4‐R‐C₆H₄)₂BX (R=H, X=Br; R=CH₃, X=Cl; R=CF₃, X=Cl) afforded the NHC‐stabilized borenium cations 10 a – c . Cyclic voltammetry revealed a linear correlation between the Hammett parameter σ _p of the para substituent and the half‐wave potential. Chemical reduction with decamethylcobaltocene, [(C₅Me₅)₂Co], furnished the corresponding radicals 11 a – c ; their characterization by EPR spectroscopy confirmed the paramagnetic character of 11 a – c , with large hyperfine coupling constants to the boron isotopes ¹¹B and ¹⁰B, while delocalization of the unpaired electron into the NHC is negligible. DFT calculations of the percentage of spin density distribution between the carbene (NHC) and the boryl fragments (BR₂) revealed for 11 a – c a spin density ratio (BR₂/NHC) of ca. 9:1, which underlines their distinct boryl radical character. The molecular structure of the most stable species 11 c was established by X‐ray diffraction analysis.     

Planar N‐Heterocyclic Carbene Diarylborenium Ions: Synthesis by Cationic Borylation and Reactivity with Lewis Bases

The NHC–borane adduct (IBn)BH₃ ( 1 ) (NHC= N‐heterocyclic carbene; IBn=1,3‐dibenzylimidazol‐2ylidene) reacts with [Ph₃C][B(C₆F₅)₄] through sequential hydride abstraction and dehydrogenative cationic borylation(s) to give singly or doubly ring closed NHC–borenium salts 2 and 3 . The planar doubly ring closed product [C₃H₂(NCH₂C₆H₄)₂B][B(C₆F₅)₄] is resistant to quaternization at boron by Et₂O coordination, but forms classical Lewis acid–base adducts with the stronger donors Ph₃P, Et₃PO, or 1,4‐diazabicyclo[2.2.2]octane (DABCO). Treatment of 3 with tBu₃P selectively yields the unusual oligomeric borenium salt trans‐[(C₃H₂(NCH₂C₆H₄)₂B)₂(C₃H₂(NCHC₆H₄)₂B)][B(C₆F₅)₄] ( 7 ).     

Bifunctional N‐Heterocyclic Carbene Catalyzed [3+4] Annulation of Enals and Aurones

Bifunctional N‐heterocyclic carbenes with a free hydroxy group are demonstrated as efficient catalysts for the [3+4] annulation of enals with aurones to give the corresponding benzofuran‐fused ε‐lactones in good yields with good diastereoselectivities and excellent enantioselectivities. Control experiments reveal that the [3+4] cycloadducts are kinetically favored and could be transformed to the thermodynamically favored [3+2] cycloadducts with a non‐bifunctional NHC catalyst.     

Access to Enantioenriched Organosilanes from Enals and β‐Silyl Enones: Carbene Organocatalysis

Herein, an efficient route to enantioenriched organosilanes, containing two consecutive stereogenic centers, from enals and β‐silyl enones under carbene organocatalysis is described. Under mild reaction conditions, this transition‐metal‐free strategy exhibits a broad substrate scope, and excellent diastereo‐ and enantioselectivity.     

Insights into the N‐Heterocyclic Carbene (NHC)‐Catalyzed Intramolecular Cyclization of Aldimines: General Mechanism and Role of Catalyst

One of the most challenging questions in the Lewis base organocatalyst field is how to predict the most electrophilic carbon for the complexation of N‐heterocyclic carbene (NHC) and reactant. This study provides a valuable case for this issue. Multiple mechanisms (A, B, C, D, and E) for the intramolecular cyclization of aldimine catalyzed by NHC were investigated by using density functional theory (DFT). The computed results reveal that the NHC energetically prefers attacking the iminyl carbon (AIC mode, which is associated with mechanisms A and C) rather than attacking the olefin carbon (AOC mode, which is associated with mechanisms B and D) or attacking the carbonyl carbon (ACC mode, which is associated with mechanism E) of aldimine. The calculated results based on the different reaction models indicate that mechanism A (AIC mode), which is associated with the formation of the aza‐Breslow intermediate, is the most favorable pathway. For mechanism A, there are five steps: (1) nucleophilic addition of NHC to the iminyl carbon of aldimine; (2) [1,2]‐proton transfer to form an aza‐Breslow intermediate; (3) intramolecular cyclization; (4) the other [1,2]‐proton transfer; and (5) regeneration of NHC. The analyses of reactivity indexes have been applied to explain the chemoselectivity, and the general principles regarding the possible mechanisms would be useful for the rational design of NHC‐catalyzed chemoselective reactions.