Oxidation and β‐Alkylation of Alcohols Catalysed by Iridium(I) Complexes with Functionalised N‐Heterocyclic Carbene Ligands

The borrowing hydrogen methodology allows for the use of alcohols as alkylating agents for C?C bond forming processes offering significant environmental benefits over traditional approaches. Iridium(I)‐cyclooctadiene complexes having a NHC ligand with a O‐ or N‐functionalised wingtip efficiently catalysed the oxidation and β‐alkylation of secondary alcohols with primary alcohols in the presence of a base. The cationic complex [Ir(NCCH₃)(cod)(MeIm(2‐ methoxybenzyl))][BF₄] (cod=1,5‐cyclooctadiene, MeIm=1‐methylimidazolyl) having a rigid O‐functionalised wingtip, shows the best catalyst performance in the dehydrogenation of benzyl alcohol in acetone, with an initial turnover frequency (TOF₀) of 1283 h^?1, and also in the β‐alkylation of 2‐propanol with butan‐1‐ol, which gives a conversion of 94 % in 10 h with a selectivity of 99 % for heptan‐2‐ol. We have investigated the full reaction mechanism including the dehydrogenation, the cross‐aldol condensation and the hydrogenation step by DFT calculations. Interestingly, these studies revealed the participation of the iridium catalyst in the key step leading to the formation of the new C?C bond that involves the reaction of an O‐bound enolate generated in the basic medium with the electrophilic aldehyde.     

Acceptorless Dehydrogenative Oxidation of Secondary Alcohols Catalysed by Cp*IrIII–NHC Complexes

A series of new Ir^III complexes with carbene ligands that contain a range of benzyl wingtip groups have been prepared and fully characterised by NMR spectroscopy, HRMS, elemental analysis and X‐ray diffraction. All the complexes were active in the acceptorless dehydrogenation of alcohol substrates in 2,2,2‐trifluoroethanol to give the corresponding carbonyl compounds. The most active complex bore an electron‐rich carbene ligand; this complex was used to catalyse the highly efficient and chemoselective dehydrogenation of a wide range of secondary alcohols to their respective ketones, with turnover numbers up to 1660. Mechanistic studies suggested that the turnover of the dehydrogenation reaction is limited by the H₂‐formation step.     

Density Functional Theory Investigation of the Alkyl–Alkyl Negishi Cross‐Coupling Reaction Catalyzed by N‐Heterocyclic Carbene (NHC)–Pd Complexes

Why bigger is better : A “steric wall” created by the N‐(2,6‐diisopropylphenyl) substituent on the bulky NHC ligand IPr (1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene) guides the reactants to and from the Pd center through weak, fleeting (IPr)H–Pd interactions that help the oxidative addition intermediate escape “the anti‐trap”. The alternative “side” approach leads to transmetalation (the rate‐limiting step) for which a novel Pd–Zn interaction was identified.

     

[(NHC)(NHCewg)RuCl2(CHPh)] Complexes with Modified NHCewg Ligands for Efficient Ring‐Closing Metathesis Leading to Tetrasubstituted Olefins

Imidazolium salts (NHC_ewg ? HCl) with electronically variable substituents in the 4,5‐position (H,H or Cl,Cl or H,NO₂ or CN,CN) and sterically variable substituents in the 1,3‐position (Me,Me or Et,Et or iPr,iPr or Me,iPr) were synthesized and converted into the respective [AgI(NHC)_ewg] complexes. The reactions of [(NHC)RuCl₂(CHPh)(py)₂] with the [AgI(NHC_ewg)] complexes provide the respective [(NHC)(NHC_ewg)RuCl₂(CHPh)] complexes in excellent yields. The catalytic activity of such complexes in ring‐closing metathesis (RCM) reactions leading to tetrasubstituted olefins was studied. To obtain quantitative substrate conversion, catalyst loadings of 0.2–0.5 mol % at 80 °C in toluene are sufficient. The complex with the best catalytic activity in such RCM reactions and the fastest initiation rate has an NHC_ewg group with 1,3‐Me,iPr and 4,5‐Cl,Cl substituents and can be synthesized in 95 % isolated yield from the ruthenium precursor. To learn which one of the two NHC ligands acts as the leaving group in olefin metathesis reactions two complexes, [(FL‐NHC)(NHC_ewg)RuCl₂(CHPh)] and [(FL‐NHC_ewg)(NHC)RuCl₂(CHPh)], with a dansyl fluorophore (FL)‐tagged electron‐rich NHC ligand (FL‐NHC) and an electron‐deficient NHC ligand (FL‐NHC_ewg) were prepared. The fluorescence of the dansyl fluorophore is quenched as long as it is in close vicinity to ruthenium, but increases strongly upon dissociation of the respective fluorophore‐tagged ligand. In this manner, it was shown for ring‐opening metathesis ploymerization (ROMP) reactions at room temperature that the NHC_ewg ligand normally acts as the leaving group, whereas the other NHC ligand remains ligated to ruthenium.     

tBuLi‐Mediated One‐Pot Direct Highly Selective Cross‐Coupling of Two Distinct Aryl Bromides

A Pd‐catalyzed direct cross‐coupling of two distinct aryl bromides mediated by tBuLi is described. The use of [Pd‐PEPPSI‐IPr] or [Pd‐PEPPSI‐IPent] as catalyst allows for the efficient one‐pot synthesis of unsymmetrical biaryls at room temperature. The key for this selective cross‐coupling is the use of an ortho‐substituted bromide that undergoes lithium–halogen exchange preferentially.     

Selective Iridium‐Catalyzed Alkylation of (Hetero)Aromatic Amines and Diamines with Alcohols under Mild Reaction Conditions

Selective amine alkylation : A P,N‐ligand‐stabilized iridium complex has been used as an efficient catalyst for the alkylation of (hetero)aromatic amines with alcohols at mild reaction temperatures and catalyst loadings as low as 0.1 mol % Ir (see scheme). The excellent selectivity of the catalyst for monoalkylation of the amine function has also been exploited for the N,N′‐dialkylation of diamines in both symmetric and nonsymmetric fashions.

     

Highly Enantioselective Aza‐Michael Reaction between Alkyl Amines and β‐Trifluoromethyl β‐Aryl Nitroolefins

The aza‐Michael addition reaction is a vital transformation for the synthesis of functionalized chiral amines. Despite intensive research, enantioselective aza‐Michael reactions with alkyl amines as the nitrogen donor have not been successful. We report the use of chiral N‐heterocyclic carbenes (NHCs) as noncovalent organocatalysts to promote a highly selective aza‐Michael reaction between primary alkyl amines and β‐trifluoromethyl β‐aryl nitroolefins. In contrast to classical conjugate‐addition reactions, a strategy of HOMO‐raising activation was used. Chiral trifluoromethylated amines were synthesized in high yield (up to 99 %) with excellent enantioselectivity (up to 98 % ee).     

Synthesis and Application of Water‐Soluble NHC Transition‐Metal Complexes

We provide an overview on the state‐of‐the‐art in transition‐metal complexes formed with water‐soluble NHC ligands. Paths to introducing water solubility by ligand design are elucidated and some general properties of water‐soluble NHC complexes are highlighted. The enhanced hydrophilicity of water‐soluble catalysts offers advantages in applications. While studies based on C? C coupling reactions still dominate the field, recent reports show water‐soluble NHC complexes can be applied in metathesis and hydrogenation reactions and turn out to be among the best performing catalysts known. Nevertheless, wide areas of this young field remain to be investigated, offering great potential for future research.     

Palladium‐Catalyzed N‐Alkylation of Amides and Amines with Alcohols Employing the Aerobic Relay Race Methodology

Possibly because homogeneous palladium catalysts are not typical borrowing hydrogen catalysts and ligands are thus ineffective in catalyst activation under conventional anaerobic conditions, they had not been used in the N‐alkylation reactions of amines/amides with alcohols in the past. By employing the aerobic relay race methodology with Pd‐catalyzed aerobic alcohol oxidation being a more effective protocol for alcohol activation, ligand‐free homogeneous palladiums are successfully used as active catalysts in the dehydrative N‐alkylation reactions, giving high yields and selectivities of the alkylated amides and amines. Mechanistic studies implied that the reaction most probably proceeds via the novel relay race mechanism we recently discovered and proposed.     

An [(NHC)(NHCEWG)RuCl2(CHPh)] Complex for the Efficient Formation of Sterically Hindered Olefins by Ring‐Closing Metathesis

NHC with EWGs for RCM : Ruthenium complexes with two N‐heterocyclic carbenes (NHCs), one of them substituted with electron‐withdrawing groups (EWGs), are highly efficient (pre)catalysts for the synthesis of tetrasubstituted olefins and trisubstituted olefins by ring‐closing metathesis reactions (RCM, see scheme).

     

Normal‐to‐Abnormal NHC Rearrangement of AlIII,GaIII, and InIII Trialkyl Complexes: Scope,Mechanism, Reactivity Studies,and H2 Activation

The present contribution reports experimental and theoretical mechanistic investigations on a normal‐to‐abnormal (C2‐to‐C4‐bonded) NHC rearrangement processes occurring with bulky group 13 metal NHC adducts, including the scope of such a reactivity for Al compounds. The sterically congested adducts (nItBu)MMe₃ (nItBu=1,3‐di‐tert‐butylimidazol‐2‐ylidene; M=Al, Ga, In; 1 a – c ) readily rearrange to quantitatively afford the corresponding C4‐bonded complexes (aItBu)MMe₃ ( 4 a – c ), a reaction that may be promoted by THF. Thorough experimental data and DFT calculations were performed on the nNHC‐to‐aNHC process converting the Al‐nNHC ( 1 a ) to its aNHC analogue 4 a . A nItBu/aItBu isomerization is proposed to account for the formation of the thermodynamic product 4 a through reaction of transient aItBu with THF–AlMe₃. The reaction of benzophenone with (nItBu)AlMe₃ afforded the zwitterionic species (aItBu)(CPh₂‐O‐AlMe₃) ( 6 ), reflecting the unusual reactivity that such bulky adducts may display. Interestingly, the nItBu/Al(iBu)₃ Lewis pair behaves like a frustrated Lewis pair (FLP) since it readily reacts with H₂ under mild conditions. This may open the way to future reactivity developments involving commonly used trialkylaluminum precursors.     

Thiazoline-Iridium (III) Complexes and Immobilized Nanomaterials as Selective Catalysts in N-Alkylation of Amines with Alcohols

In this research, a new series of thiazoline-iridium (III) complexes ( 4 – 7 ) derived from cysteine were prepared and fully characterized by conventional methods. The molecular structure of complex 5 was also determined by single-crystal X-ray diffraction. These complexes were evaluated as catalysts for hydrogen-borrowing reactions of amines with alcohols. In particular, complex 5 showed the best activity as catalyst. Various amines have been alkylated with alcohols affording moderate to good yield (33–99%). Moreover, the immobilized nanomaterials ( M _1,2 ) were fabricated by sonication process from the best catalyst 5 with the multi-walled carbon nanotubes (MWCNTs) and graphene oxide (GO), respectively, and characterized by X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray (EDX) spectroscopy, and inductively coupled plasma-mass spectrometry (ICP-MS). The M _1,2 nanomaterials were also tested as catalysts in model catalytic reaction for N-alkylation. The M ₁ nanomaterial showed significantly higher activity than the M ₂ nanomaterial. The M ₁ catalyst was recovered by filtration and reused for four catalytic cycles with high conversion (99%, 97%, 96%, and 86%).     

CO2 and SnII Adducts of N‐Heterocyclic Carbenes as Delayed‐Action Catalysts for Polyurethane Synthesis

Catalytic rivals : Both CO₂‐protected tetrahydropyrimidin‐2‐ylidene‐based N‐heterocyclic carbenes (NHCs) and Sn^II‐1,3‐dimesitylimidazol‐2‐ylidene, as well as Sn^II‐1,3‐dimesitylimidazolin‐2‐ylidene complexes (example displayed), have been identified as truly latent catalysts for polyurethane (PUR) synthesis rivaling all existing systems both in activity and latency.

     

Oxidative Addition of 2‐Halogenoazoles—Direct Synthesis of Palladium(II) Complexes Bearing Protic NH,NH‐Functionalized NHC Ligands

The chemistry of N‐heterocyclic carbenes (NHCs) is dominated by N,N′‐dialkylated or ‐diarylated derivatives. Such NHC ligands are normally obtained by C2‐deprotonation of azolium cations or by reductive elimination from azol‐2‐thiones. A simple one‐step procedure is described that leads to complexes with NH,NH‐functionalized NHC ligands by the oxidative addition of 2‐halogenoazoles to complexes of zero‐valent transition metals.     

Direct Catalytic Addition of Alkylnitriles to Aldehydes by Transition‐Metal/NHC Complexes

Direct catalytic addition of alkylnitriles to aldehydes allows for an atom‐economical access to β‐hydroxynitriles under proton transfer conditions. Direct use of alkylnitriles as pronucleophiles has been hampered due to their low acidity resulting in an inability to generate α‐cyano carbanions in a catalytic manner. A transition metal/N‐heterocyclic carbene (NHC) complex prepared from [{Rh(OMe)(cod)}₂] and an imidazolium‐based carbene was identified as an effective catalyst to promote the reaction with as little as 1.25 mol % of catalyst loading. The corresponding Rh complex, derived from chiral triazolium salt, rendered the reaction enantioselective, albeit with moderate enantioselectivity.