Enantioselective Synthesis of Spirocyclohexadienones by NHC‐Catalyzed Formal [3+3] Annulation Reaction of Enals

The enantioselective synthesis of pyrazolone‐fused spirocyclohexadienones was demonstrated by the reaction of α,β‐unsaturated aldehydes with α‐arylidene pyrazolinones under oxidative N‐heterocyclic carbene (NHC)catalysis. This atom‐economic and formal [3+3] annulation reaction proceeds through a vinylogous Michael addition/spiroannulation/dehydrogenation cascade to afford spirocyclic compounds with an all‐carbon quaternary stereocenter in moderate to good yields and excellent ee values. Key to the success of the reaction is the cooperative NHC‐catalyzed generation of chiral α,β‐unsaturated acyl azoliums from enals, and base‐mediated tandem generation of dienolate/enolate intermediates from pyrazolinones.     

NHC‐Catalyzed Asymmetric Synthesis of Functionalized Succinimides from Enals and α‐Ketoamides

The efficient asymmetric synthesis of highly substituted succinimides from α,β‐unsaturated aldehydes and α‐ketoamides via NHC‐catalyzed [3+2] cycloaddition has been developed. The new scalable protocol significantly expands the utility of NHC catalysis for the synthesis of heterocycles and provides easy access to assemble a wide range of succinimides from simple starting materials.     

A Cooperative N‐Heterocyclic Carbene/Chiral Phosphate Catalysis System for Allenolate Annulations

The highly enantioselective NHC‐catalyzed [3+2] annulation reaction with α,β‐alkynals and α‐ketoesters has been developed. A new mode of cooperative catalysis involving the combination of a chiral Brønsted acid and a C₁‐symmetric biaryl saturated‐imidazolium precatalyst was required to generate the desired γ‐crotonolactones in high yields and levels of enantioselectivity.     

Ionic Pd/NHC Catalytic System Enables Recoverable Homogeneous Catalysis: Mechanistic Study and Application in the Mizoroki–Heck Reaction

N-Heterocyclic carbene (NHC) ligands are ubiquitously utilized in catalysis. A common catalyst design model assumes strong M–NHC binding in this metal–ligand framework. In contrast to this common assumption, we demonstrate here that lability and controlled cleavage of the M−NHC bond (rather than its stabilization) could be more important for high-performance catalysis at low catalyst concentrations. The present study reveals a dynamic stabilization mechanism with labile metal–NHC binding and [PdX₃]⁻[NHC-R]⁺ ion pair formation. Access to reactive anionic palladium intermediates formed by dissociation of the NHC ligands and plausible stabilization of the molecular catalyst in solution by interaction with the [NHC-R]⁺ azolium ion is of particular importance for an efficient and recyclable catalyst. These ionic Pd/NHC complexes allowed for the first time the recycling of the complex in a well-defined form with isolation at each cycle. Computational investigation of the reaction mechanism confirms a facile formation of NHC-free anionic Pd in polar media through either Ph–NHC coupling or reversible H–NHC coupling. The present study formulates novel ideas for M/NHC catalyst design.     

An N-heterocyclic carbene/Lewis acid strategy for the stereoselective synthesis of spirooxindole lactones

A cooperative catalysis approach for the enantioselective formal [3+2] addition of α,β-unsaturated aldehydes to isatins has been developed. Homoenolate annulations of β-aryl enals catalyzed by an N-heterocyclic carbene (NHC) require the addition of lithium chloride for high levels of enantioselectivity. This NHC-catalyzed annulation has been used for the total synthesis of maremycin B.     

基于非血红素铁模型配合物[FeⅣ(O)(N4Py)]2+的新型N杂环卡宾配合物的理论设计

基于四价非血红素铁模型配合物[FeⅣ(O)(N4Py)]2+, 通过理论计算设计出一种新型N杂环卡宾配合物[FeⅣ(O)(N4Py)]2+. 采用密度泛函理论B3LYP方法, 计算了[FeⅣ(O)(N4Py)]2+的几何结构和电子结构, 并研究了[FeⅣ(O)(N4Py)]2+使环己烷C-H键羟基化的反应机理. 结果表明, [FeⅣ(O)(N4Py)]2+的五重态能量比基态三重态能量高约5.7 kJ/mol, 故五重态几乎不能参与反应. 赤道方向的配位基N杂环卡宾(NHC)对FeO单元的σ-贡献要大于N4Py的贡献, 而它的空间位阻效应也大于N4Py, 因此2+的稳定性强于[FeⅣ(O)(N4Py)]2+. [FeⅣ(O)(N4Py)]2+的三重态的反应能垒比[FeⅣ(O)(N4Py)]2+的三重态反应能垒高2.0 kJ/mol, 且为单态反应, 所以[FeⅣ(O)(N4Py)]2+的反应活性要高于[FeⅣ(O)(N4Py)]2+.     

N‐Heterocyclic Carbene Catalyzed Formal [3+2] Annulation Reaction of Enals: An Efficient Enantioselective Access to Spiro‐Heterocycles

A highly enantioselective N‐heterocyclic carbene (NHC) catalyzed formal [3+2] annulation of α,β‐unsaturated aldehydes with azaaurones or aurone generating spiro‐heterocycles has been developed. The protocol represents a unique NHC‐activation‐based approach to access spiro‐heterocyclic derivatives bearing a quaternary stereogenic center with high optical purity (up to 95 % ee).     

How to Bend a Cumulene

Allenes (carbodicarbenes) and [3]cumulenes are linear carbon chains that can be bent when the terminal group has a strong carbene nature. This bending can be quite pronounced in allenes but not in [3]cumulenes. In this study, how N-heterocyclic or cyclic (alkyl)(amino) carbene (NHC and CAAC, respectively) terminal groups can modify the linear structure of [n]cumulenes has been analyzed. A low π acidity of the terminal carbene affects the linearity of [2n]cumulenes. Indeed, it has been found that the NHC [4]cumulene is extremely bent, contrary to classical [4]cumulenes. The predicted NHC [4]cumulene or tricarbodicarbene has two lone pairs and the π electrons are delocalized over the whole molecule. More significantly, DFT calculations have shown that this bent [4]cumulene is very stable, considerably more so than the corresponding [3]cumulene, which has been elusive to synthesize. Remarkably, calculations have shown that all the NHC [2n]cumulenes are more than 25 kcal mol⁻¹ more stable than the [2n−1]cumulenes.     

N‐Heterocyclic Carbene‐Catalyzed [2+2+2] Annulation of Allenoates with Trifluoromethylketones

In contrast with the reported phosphine‐ and DABCO‐catalyzed [3+2] and [2+2] annulation of allenoates with trifluoromethylketone, the [2+2+2] annulation of allenoates and two molecules of trifluoromethylketone was found under the condition of N‐heterocyclic carbene catalysis.     

Prediction on the Origin of Selectivities in Base‐controlled Switchable NHC‐catalyzed Transformations

The base‐controlled mechanisms for N‐heterocyclic carbene (NHC)‐catalyzed divergent [3+3] and [3+2] annulation reactions were examined by using the DFT method. The reaction initiates with the complexation of NHC and enal to give the Breslow intermediate, which diverges afterward. Then, the azomethine imine can either react with the Breslow intermediate to give the six‐membered ring product or the β‐carbon protonation occurs for forming the enolate intermediate controlled by different bases. The formed enolate intermediate reacts with azomethine imine to afford the five‐membered ring product. The calculated results show that only the base K₂CO₃ can facilitate the structural transformation between homoenolate and enolate to switch the chemoselectivity; therefore, the [3+3] annulation happens preferentially in the presence of base DBU while the other situation occurs with K₂CO₃ as base. The NCI analysis results reveal that the stereoselectivity is predominately determined by the π???π, C?H???O, and C?H???N interactions. The obtained mechanistic insights should provide valuable clues for the rational design of these kinds of divergent reactions.     

Carbene‐Catalyzed Enantioselective Decarboxylative Annulations to Access Dihydrobenzoxazinones and Quinolones

A direct decarboxylative strategy for the generation of aza‐o‐quinone methides (aza‐o‐QMs) by N‐heterocyclic carbene (NHC) catalysis has been discovered and explored. This process requires no stoichiometric additives in contrast with current approaches. Aza‐o‐QMs react with trifluoromethyl ketones through a formal [4+2] manifold to access highly enantioenriched dihydrobenzoxazin‐4‐one products, which can be converted to dihydroquinolones through an interesting stereoretentive aza‐Petasis–Ferrier rearrangement sequence. Complementary dispersion‐corrected density functional theory (DFT) studies provided an accurate prediction of the reaction enantioselectivity and lend further insight to the origins of stereocontrol. Additionally, a computed potential energy surface around the major transition structure suggests a concerted asynchronous mechanism for the formal annulation.     

Synthesis,structure, and properties of the Sc chloride complex coordinated by the tridentate bis(phenolate)-tethered NHC ligand

The scandium chloride complex LScCl(py)₂ (L is bis[(2,4-di-tert-butyl)phenolato]-6,6′-(4,5-dihydroimidazol-2-ylidene)) containing the dianionic bis(phenolate)-tethered N-heterocyclic carbene (NHC) ligand was synthesized. The X-ray diffraction study demonstrated that the complex has a mononuclear structure with intramolecular coordination of the carbene moiety to the Sc³⁺ ion. In the presence of moist air, the NHC moiety is hydrolyzed, resulting in the formation of the chloride complex [L’ScCl(py)]₂ with the dianionic tetradentate bis(phenolate) ligand containing the [NH(CH)₂N(HC=O)] linker. The binuclear complex [L’ScClpy]₂ is formed through the coordination of the oxygen atom of the formylethylenediamine moiety to the second Sc³⁺ ion.

     

Reaction of an N‐Heterocyclic Carbene‐Stabilized Silicon(II) Monohydride with Alkynes: [2+2+1] Cycloaddition versus Hydrogen Abstraction

An in depth study of the reactivity of an N‐heterocyclic carbene (NHC)‐stabilized silylene monohydride with alkynes is reported. The reaction of silylene monohydride 1 , tBu₃Si(H)Si←NHC, with diphenylacetylene afforded silole 2 , tBu₃Si(H)Si(C₄Ph₄). The density functional theory (DFT) calculations for the reaction mechanism of the [2+2+1] cycloaddition revealed that the NHC played a major part stabilizing zwitterionic transition states and intermediates to assist the cyclization pathway. A significantly different outcome was observed, when silylene monohydride 1 was treated with phenylacetylene, which gave rise to supersilyl substituted 1‐alkenyl‐1‐alkynylsilane 3 , tBu₃Si(H)Si(CH?CHPh)(C?CPh). Mechanistic investigations using an isotope labelling technique and DFT calculations suggest that this reaction occurs through a similar zwitterionic intermediate and subsequent hydrogen abstraction from a second molecule of phenylacetylene.     

An Original L‐shape,Tunable N‐Heterocyclic Carbene Platform for Efficient Gold(I) Catalysis

The synthesis and characterization of original NHC ligands based on an imidazo[1,5‐a]pyridin‐3‐ylidene (IPy) scaffold functionalized with a flanking barbituric heterocycle is described as well as their use as tunable ligands for efficient gold‐catalyzed C?N, C?O, and C?C bond formations. High activity, regio‐, chemo‐, and stereoselectivities are obtained for hydroelementation and domino processes, underlining the excellent performance (TONs and TOFs) of these IPy‐based ligands in gold catalysis. The gold‐catalyzed domino reactions of 1,6‐enynes give rise to functionalized heterocycles in excellent isolated yields under mild conditions. The efficiency of the NHC gold 5^Me complex is remarkable and mostly arises from a combination of steric protection and stabilization of the cationic Au^I active species by ligand 1^Me .     

An Original L‐shape,Tunable N‐Heterocyclic Carbene Platform for Efficient Gold(I) Catalysis

The synthesis and characterization of original NHC ligands based on an imidazo[1,5‐a]pyridin‐3‐ylidene (IPy) scaffold functionalized with a flanking barbituric heterocycle is described as well as their use as tunable ligands for efficient gold‐catalyzed C?N, C?O, and C?C bond formations. High activity, regio‐, chemo‐, and stereoselectivities are obtained for hydroelementation and domino processes, underlining the excellent performance (TONs and TOFs) of these IPy‐based ligands in gold catalysis. The gold‐catalyzed domino reactions of 1,6‐enynes give rise to functionalized heterocycles in excellent isolated yields under mild conditions. The efficiency of the NHC gold 5^Me complex is remarkable and mostly arises from a combination of steric protection and stabilization of the cationic Au^I active species by ligand 1^Me .     

Development of building blocks for the synthesis of N-heterocyclic carbene ligands

[reaction: see text] The synthesis of a series of NHC building blocks that can then be incorporated into more complicated structures by palladium catalysis is reported. This approach is used for the synthesis of three amino acids containing NHC side chains. The ability to use the amino acids in solid-phase peptide synthesis to make NHC-containing peptides is also demonstrated. Additionally, the NHC side chain can be deprotected and coordinated to a catalytically active transition metal. Finally, it is illustrated that the building blocks participate in Suzuki coupling to provide access to substituted NHC ligands.     

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.     

Unexpected Vulnerability of DPEphos to C−O Activation in the Presence of Nucleophilic Metal Hydrides

C−O bond activation of DPEphos occurs upon mild heating in the presence of [Ru(NHC)₂(PPh₃)₂H₂] (NHC=N-heterocyclic carbene) to form phosphinophenolate products. When NHC=IEt₂Me₂, C−O activation is accompanied by C−N activation of an NHC ligand to yield a coordinated N-phosphino-functionalised carbene. DFT calculations define a nucleophilic mechanism in which a hydride ligand attacks the aryl carbon of the DPEphos C−O bond. This is promoted by the strongly donating NHC ligands which render a trans dihydride intermediate featuring highly nucleophilic hydride ligands accessible. C−O bond activation also occurs upon heating cis-[Ru(DPEphos)₂H₂]. DFT calculations suggest this reaction is promoted by the steric encumbrance associated with two bulky DPEphos ligands. Our observations that facile degradation of the DPEphos ligand via C−O bond activation is possible under relatively mild reaction conditions has potential ramifications for the use of this ligand in high-temperature catalysis.     

Four-coordinate N-heterocyclic carbene (NHC) copper(I) complexes with brightly luminescence properties

Three four-coordinate N-heterocyclic carbene (NHC) copper(I) complexes, [Cu(Py-Im)(POP)](PF₆) (P1), [Cu(Py-BenIm)(POP)](PF₆) (P2), and [Cu(Py-c-BenIm)(POP)](PF₆) (P3) (Py-Im = 3-methyl-1-(pyridin-2-yl)-1H-imidazolylidene, Py-BenIm = 3-methyl-1-(pyridin-2-yl)-1H-benzo[d]imidazolylidene, Py-c-BenIm = 3-methyl-1-(pyridin-2-ylmethyl)-1H-benzo[d]imidazolylidene, POP = bis([2-diphenylphosphino]-phenyl)ether), have been synthesized without transmetalation of the NHC–Ag(I) complex for the first time. The photophysical properties of the resultant NHC–Cu(I) complexes have been systematically investigated via spectroscopic methods. All complexes exhibit good photoluminescence properties with long excited-state lifetimes and moderate quantum yields. Density functional theory and time dependent density functional theory calculations were employed to rationalize the photophysical properties of the NHC–Cu(I) complexes.     

Structural motifs of Au(I)-Cu(I) N-heterocyclic carbene halide complexes

A series of Au(I)–Cu(I) N-heterocyclic carbene (NHC) halide complexes [AuCu₂(im(CH₂py)₂)₂X]²⁺ where X?=?Cl (1), Br (2), I (3) was prepared by refluxing [AuCu₂(im(CH₂py)₂)₂(NCCH₃)₄]³⁺ with the appropriate halide in acetonitrile. The compounds were characterized by NMR, absorption, and fluorescence spectroscopy. They feature similar solution behavior and solid-state photoemissions. The solid-state structures feature a rhomboidal [AuCu₂X]²⁺ core which is influenced by the type of halide. Compared to other Au(I)–Cu(I) NHC complexes, 1–3 comprise a new structural motif containing a bridging halide. The benzimidazolium analog of 1 was also characterized crystallographically. The structure of [AuCu₂(benzim(CH₂py)₂)₂Cl]²⁺(4) features different coordination modes of the NHC ligands with the carbenic carbon bonded to both gold and copper and the pyridyl groups bonded to the same copper(I) ion.