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.

     

Triazole‐Functionalized N‐Heterocyclic Carbene Complexes of Palladium and Platinum and Efficient Aqueous Suzuki–Miyaura Coupling Reaction

Imidazolium salts bearing triazole groups are synthesized via a copper catalyzed click reaction, and the silver, palladium, and platinum complexes of their N‐heterocyclic carbenes are studied. [Ag₄(L1)₄](PF₆)₄, [Pd(L1)Cl](PF₆), [Pt(L1)Cl](PF₆) (L1=3‐((1‐benzyl‐1H‐1,2,3‐triazol‐4‐yl)methyl)‐1‐(pyrimidin‐2‐yl)‐1H‐imidazolylidene), [Pd₂(L2)₂Cl₂](PF₆)₂, and [Pd(L2)₂](PF₆)₂ (L2=1‐butyl‐3‐((1‐(pyridin‐2‐yl)‐1H‐1,2,3‐triazol‐4‐yl)methyl)imidazolylidene) have been synthesized and fully characterized by NMR, elemental analysis, and X‐ray crystallography. The silver complex [Ag₄(L1)₄](PF₆)₄ consists of a Ag₄ zigzag chain. The complexes [Pd(L1)Cl](PF₆) and [Pt(L1)Cl](PF₆), containing a nonsymmetrical NCN ′ pincer ligand, are square planar with a chloride trans to the carbene donor. [Pd₂(L2)₂Cl₂](PF₆)₂ consists of two palladium centers with CN₂Cl coordination mode, whereas the palladium in [Pd(L2)₂](PF₆)₂ is surrounded by two carbene and two triazole groups with two uncoordinated pyridines. The palladium compounds are highly active for Suzuki–Miyaura cross coupling reactions of aryl bromides and 1,1‐dibromo‐1‐alkenes in neat water under an air atmosphere.     

PEG Click‐Triazole Palladacycle: An Efficient Precatalyst for Palladium‐Catalyzed Suzuki‐Miyaura and Copper‐free Sonogashira Reactions in Neat Water

A novel water‐soluble, phosphine‐free PEG "click" triazole palladacycle has been successfully synthesized. As a precatalyst, the palladacycle exhibited superior catalytic activity towards Suzuki‐Miyaura and copper‐free Sonogashira cross‐coupling in neat water with the turnover numbers (TONs) of up to 9.8×10⁵. In addition, the catalyst could be reused at least 3 times without significant loss of reactivity.     

Tandem Chemoselective Suzuki–Miyaura Cross‐Coupling Enabled by Nucleophile Speciation Control

Control of boronic acid speciation is presented as a strategy to achieve nucleophile chemoselectivity in the Suzuki–Miyaura reaction. Combined with simultaneous control of oxidative addition and transmetalation, this enables chemoselective formation of two C? C bonds in a single operation, providing a method for the rapid preparation of highly functionalized carbogenic frameworks.     

Practical Iron‐ and Cobalt‐Catalyzed Cross‐Coupling Reactions between N‐Heterocyclic Halides and Aryl or Heteroaryl Magnesium Reagents

The reaction scope of iron‐ and cobalt‐catalyzed cross‐coupling reactions in the presence of isoquinoline (quinoline) in the solvent mixture tBuOMe/THF has been further investigated. Various 2‐halogenated pyridine, pyrimidine, and triazine derivatives were arylated under these mild conditions in excellent yields. The presence of isoquinoline allows us to perform Fe‐catalyzed cross‐coupling reactions between 6‐chloroquinoline and aryl magnesium reagents. Furthermore, it was found that the use of 10 % N,N‐dimethylquinoline‐8‐amine increases the yields of some Co‐catalyzed cross‐coupling reactions with chloropyridines bearing electron‐withdrawing substituents.     

Speciation Control During Suzuki–Miyaura Cross‐Coupling of Haloaryl and Haloalkenyl MIDA Boronic Esters

Boronic acid solution speciation can be controlled during the Suzuki–Miyaura cross‐coupling of haloaryl N‐methyliminodiacetic acid (MIDA) boronic esters to enable the formal homologation of boronic acid derivatives. The reaction is contingent upon control of the basic biphase and is thermodynamically driven: temperature control provides highly chemoselective access to either BMIDA adducts at room temperature or boronic acid pinacol ester (BPin) products at elevated temperature. Control experiments and solubility analyses have provided some insight into the mechanistic operation of the formal homologation process.     

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.     

Palladium‐Catalyzed Suzuki‐Miyaura Type Coupling Reaction of Aryl Halides with Triphenylborane‐Pyridine

The Suzuki‐Miyaura type coupling reaction of aryl halides with triphenylborane‐pyridine was described. The reaction can be catalyzed by Pd(OAc)₂ (5 mol%) in presence of Cs₂CO₃ at 50°C or 80°C, and functionalized biaryls were obtained in good to excellent yields. This protocol is general and can tolerate a wide range of functional groups.     

Palladium‐Catalyzed Direct C2‐Arylation of an N‐Heterocyclic Carbene: An Atom‐Economic Route to Mesoionic Carbene Ligands

Blocking the C2 position of an imidazole‐derived classical N‐heterocyclic carbene (NHC) with an aryl group is an essential strategy to establish a route to mesoionic carbenes (MICs), which coordinate to the metal via the C4 (or C5) carbon atom. An efficient catalytic route to MIC precursors by direct arylation of an NHC is reported. Treatment of 1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene (IPr) with an aryl iodide (RC₆H₄I) in the presence of 0.5 mol % of [Pd₂(dba)₃] (dba=dibenzylideneacetone) precatalyst affords the C2‐arylated imidazolium salts {IPr(C₆H₄R)}I (R=H, 4‐Me, 2‐Me, 4‐OMe, 4‐COOMe) in excellent (up to 92 %) yields. Treatment of {IPr(C₆H₅)}I with CuI and KN(SiMe₃)₂ exclusively affords the MIC–copper complex [(IPrPh)CuI].