Bond Cross-Coupling Research Articles

Nickel-catalysed reductive C-N bond cross-coupling between aryl halides and N-chloroamides.

A method for the direct synthesis of N-aryl lactams and amides with aryl halides and N-chloroamides through a Ni-catalyzed reductive C-N coupling reaction has been developed. The reaction features the advantages of mild conditions, good functional group tolerance and broad substrate scope including drug-derived substrates, and also provided direct access to the key synthetic intermediates for some bioactive molecules, suggesting the practicability of this method. Finally, DFT calculations were performed to shed further light on the reaction mechanism and it was found that an amidyl radical might be involved.

Stereospecific Cu(I)-Catalyzed C-O Cross-Coupling Synthesis of Acyclic 1,2-Di- and Trisubstituted Vinylic Ethers from Alcohols and Vinylic Halides.

CuI and trans-N,N'-dimethylcyclohexyldiamine catalyze the single-step C-O bond cross-coupling between 1,2-di- and trisubstituted vinylic halides with functionalized alcohols, producing acyclic vinylic ethers. This stereospecific transformation selectively gives each of the (E)- and (Z)-vinylic ether products from the corresponding vinyl halide precursors. This method is compatible with carbohydrate-derived primary and secondary alcohols and several other functional groups. The conditions are mild enough to reliably generate vinylic allylic ethers without promoting Claisen rearrangements.

Transition-Metal Free C–C Bond Cross-Coupling of Aryl Ethers with Diarylmethanes

We describe a general and efficient transition-metal free C-C bond cross-coupling of (hetero)aryl ethers and diarylmethanes via C(sp2)-O bond cleavage. The coupling reactions mediated by KHMDS proceeded well with high efficiency, broad substrate scope, and good functional group tolerance. The robustness and practicability of this protocol also have been demonstrated by easy gram-scale preparation and diversified product derivatization.

Theoretical Mechanistic Study of C(sp3 )-C(sp2 ) Cross-Coupling by Photoredox-Mediated Iridium(III)/Nickel(II)/Quinuclidine Triple Catalysis.

The photoredox-mediated iridium(III)/nickel(II)/3-acetoxyquinuclidine triple-synergistic catalysis was comprehensively investigated by taking a C(sp3 )-C(sp2 ) bond cross-coupling as a reaction model using density functional theory (DFT) calculations. The synergistic mechanism of the triple catalytic system includes a reductive quenching cycle (IrIII -*IrIII -IrII -IrIII ), an organocatalytic cycle, and a nickel catalytic cycle (NiII -NiI -NiIII -[NiIII ]⊖ -NiII ). Electronic process analysis shows that 3-acetoxyquinuclidine acts as a hydrogen atom transfer (HAT) catalyst to regioselectively provide α-carbon centered radical. Due to more favorable oxidative addition of C-Br to Ni(I) than HAT to avoid the formation of stable Ni(II) species, the generated α-carbon centered radical prefers to be captured by oxidative addition product Ni(III) to form an unusual [NiIII ]⊖ C⊕ species when 3-acetoxyquinuclidine was employed. These theoretical insights not only provide deep electronic process understanding of the photoredox-mediated iridium(III)/nickel(II) synergistic catalysis, but also clarify the electron-withdrawing group effect of quinuclidine, which has a potential guiding role for further development of new cross-coupling reactions.

Bifunctionality of Zn dust in Ullmann C–C cross-coupling by Ni/Pd dual catalysis: theoretical insight

Zinc powder presents bifunctionality for heterogeneous single-electron reduction and homogeneous transmelation in Ullmann C–C bond cross-coupling by Ni/Pd dual catalysis.

A radical mechanism for C–H bond cross-coupling and N2activation catalysed by β-diketiminate iron complexes

Density functional theory calculations and electronic structure analyses reveal a radical mechanism with spin-crossovers for C–H bond cross-coupling and N2activation catalysed by β-diketiminate iron complexes.

Mechanosynthesis of polymeric and binuclear copper complexes via dehydrochlorination and their application in solvent-free C–S bond cross-coupling

Two copper complexes are readily synthesized from their respective salts by dehydrochlorination reactions and then used as catalysts in mechanosynthesis C–S coupling reactions.

Evaluation of Cyclic Amides as Activating Groups in N-C Bond Cross-Coupling: Discovery of N-Acyl-δ-valerolactams as Effective Twisted Amide Precursors for Cross-Coupling Reactions.

The development of efficient methods for facilitating N-C(O) bond activation in amides is an important objective in organic synthesis that permits the manipulation of the traditionally unreactive amide bonds. Herein, we report a comparative evaluation of a series of cyclic amides as activating groups in amide N-C(O) bond cross-coupling. Evaluation of N-acyl-imides, N-acyl-lactams, and N-acyl-oxazolidinones bearing five- and six-membered rings using Pd(II)-NHC and Pd-phosphine systems reveals the relative reactivity order of N-activating groups in Suzuki-Miyaura cross-coupling. The reactivity of activated phenolic esters and thioesters is evaluated for comparison in O-C(O) and S-C(O) cross-coupling under the same reaction conditions. Most notably, the study reveals N-acyl-δ-valerolactams as a highly effective class of mono-N-acyl-activated amide precursors in cross-coupling. The X-ray structure of the model N-acyl-δ-valerolactam is characterized by an additive Winkler-Dunitz distortion parameter Σ(τ+χN) of 54.0°, placing this amide in a medium distortion range of twisted amides. Computational studies provide insight into the structural and energetic parameters of the amide bond, including amidic resonance, N/O-protonation aptitude, and the rotational barrier around the N-C(O) axis. This class of N-acyl-lactams will be a valuable addition to the growing portfolio of amide electrophiles for cross-coupling reactions by acyl-metal intermediates.

Merging Electron Transfer with 1,2-Metalate Rearrangement: Deoxygenative Arylation of Aromatic Amides with Arylboronic Esters.

Amides are essentially inert carboxyl derivatives in many types of chemical transformations. In particular, deoxygenative C-C bond formation of amides to synthetically important amines is a long-standing challenge for synthetic chemists due to the inertness of the resonance-stabilized amide C=O bond. Herein, it is disclosed that by merging electron-transfer-induced activation with 1,2-metalate rearrangement, a wide range of aromatic amides react smoothly with arylboron reagents, affording a series of biologically relevant diarylmethylamines as deoxygenative C-C bond cross-coupling products. With its simplicity and versatility, this reaction shows great promise in the synthesis of amines from amides, which may open up new avenues in retrosynthetic planning and find widespread use in academia and industry.

Investigation of Stepwise and Stoichiometric Palladium-Mediated ortho-C–H Bond Arylation and Alkylation of 9(10H)-Acridinone

We present a stoichiometric methodology for the synthesis of 4-arylated/alkylated 9(10H)-acridinones via a palladium-mediated ortho-C–H bond activation and C–C bond cross-coupling strategy. In the ...

Cu2O-catalyzed C–S coupling of quaternary ammonium salts and sodium alkane-/arene-sulfinates

A new protocol for the synthesis of (enantioenriched) benzylic sulfones via the Cu2O-catalyzed C–S bond cross coupling of alkane-/arene-sulfinates and (enantioenriched) benzylic quaternary ammonium salts has been developed. The product benzylic sulfones were obtained in good to high yields (75–96%). Chiral arylmethyl sulfones with high enantiomeric excess (90–94% ee) were also synthesized in the presence of Cu2O and 1,1′-bis-(diphenylphosphino)ferrocene (dppf).

Synthesis of Dibenzosuberones Bearing an Isoxazole Group via Palladium-Catalyzed Intramolecular C–H/C–Br Bond Cross-Coupling of Ortho-Aroylated 3,5-Diarylisoxazoles

A facile and efficient synthetic methodology for preparing dibenzosuberones via a C-H bond activation strategy is presented. The ortho-aroylated 3,5-diarylisoxazole was employed as the starting substrate to undergo palladium-catalyzed intramolecular C-H/C-Br bond cross-coupling to produce a variety of dibenzosuberones bearing an isoxazole group in 24 to >99% 1H NMR yields. The dibenzosuberone structure was further confirmed by X-ray crystallography. The developed methodology exhibits very good functional group tolerance. In addition, a rational mechanism was presented for describing the reaction process. For the prepared dibenzosuberone, the use of Mo(CO)6 as the catalyst can easily transform the isoxazole ring into the β-aminoenone group. Finally, the structure of the anticipated ring-opening product, dibenzosuberenone, bearing a β-amino-α-ketone group was secured by X-ray crystallography.

N-Acyl-glutarimides: Effect of Glutarimide Ring on the Structures of Fully Perpendicular Twisted Amides and N–C Bond Cross-Coupling

N-Acyl-glutarimides have emerged as the most reactive precursors for N-C(O) bond cross-coupling reactions to date, wherein the reactivity is driven by ground-state destabilization of the amide bond. Herein, we report a full study on the effect of a glutarimide ring on the structures, electronic properties, and reactivity of fully perpendicular N-acyl-glutarimide amides. Most notably, this report demonstrates the generality of deploying N-acyl-glutarimides to achieve full twist of the acyclic amide bond, and results in the discovery of N-acyl-glutarimide amide with an almost perfect twist value, τ = 89.1°. X-ray structures of five new N-acyl-glutarimides are reported. Reactivity studies in the Suzuki-Miyaura cross-coupling and transamidation reactions provide insight into the reactivity of N-acyl-glutarimides in metal-catalyzed and transition-metal-free reactions. The effect of distortion, structures, and rotational barriers around the N-C(O) axis is discussed. The ability to achieve full distortion of the amide bond significantly expands the range of reagents available for N-C(O) cross-coupling reactions.

An efficient method for the synthesis of 2-pyridones via C-H bond functionalization.

A simple and practical method to access N-substituted 2-pyridones via a formal [3+3] annulation of enaminones with acrylates based on RhIII-catalyzed C-H functionalization was developed. Control and deuterated experiments led to a plausible mechanism involving C-H bond cross-coupling and aminolysis cyclization. This strategy provides a short synthesis of structural motifs of N-substituted 2-pyridones.

Transition-metal mediated carbon-sulfur bond activation and transformations: an update.

Carbon-sulfur bond cross-coupling has become more and more attractive as an alternative protocol to establish carbon-carbon and carbon-heteroatom bonds. Diverse transformations through transition-metal-catalyzed C-S bond activation and cleavage have recently been developed. This review summarizes the advances in transition-metal-catalyzed cross-coupling via carbon-sulfur bond activation and cleavage since late 2012 as an update of the critical review on the same topic published in early 2013 (Chem. Soc. Rev., 2013, 42, 599-621), which is presented by the categories of organosulfur compounds, that is, thioesters, thioethers including heteroaryl, aryl, vinyl, alkyl, and alkynyl sulfides, ketene dithioacetals, sulfoxides including DMSO, sulfones, sulfonyl chlorides, sulfinates, thiocyanates, sulfonium salts, sulfonyl hydrazides, sulfonates, thiophene-based compounds, and C[double bond, length as m-dash]S functionality-bearing compounds such as thioureas, thioamides, and carbon disulfide, as well as the mechanistic insights. An overview of C-S bond cleavage reactions with stoichiometric transition-metal reagents is briefly given. Theoretical studies on the reactivity of carbon-sulfur bonds by DFT calculations are also discussed.

MOF nano porous-supported C-S cross coupling through one-pot post-synthetic modification

UIO-66-NH2-Fu@Ni has been synthesized by anchoring a molecular nickel furfural (Fu) complex into a functionalized nanoporous metal-organic framework (MOF) with the amine functional groups, using the one-pot post-synthetic modification. This new catalyst was identified via Fourier-transform infrared (FT-IR) spectroscopy, proton-nuclear-magnetic-resonance (1HNMR) spectroscopy, nitrogen gas adsorption-desorption method, thermogravimetric analyses (TGA), energy-dispersive X-ray- mapping spectroscopy (EDX-MAP), field emission scanning electron microscopy (FE-SEM), and X-ray diffraction (XRD). 1HNMR analysis showed that around 16% of the amine functional groups of the nanocrystalline UIO-66-NH2 framework were modified with nickel complex. Also, according to the inductive couple plasma atomic emission spectroscopy (ICP), around 2.98 w% of Ni was determined in the modified MOF. The Ni complex which was supported by UIO-66-NH2 nanocatalyst was effectively used as a heterogeneous catalyst for the formation of sulfur-containing molecules such as thioethers which are generally found in chemical biology, organic synthesis, and materials chemistry through the C-S bond cross-coupling of aryl iodides with thiols. UIO-66-NH2-Fu@Ni propagated the condensation reaction by different aryl iodides and aryl thiols in moderate conditions in the presence of K2CO3 as a base in high reaction yield during 8–14 h. The Ni complex which was supported by UIO-66-NH2 nanocatalyst was simply recycled and reused thrice while its catalytic activity was maintained approximately.

Palladium-Catalyzed C(sp2)-N Bond Cross-Coupling with Triaryl Phosphates.

The first general palladium-catalyzed amination of aryl phosphates is described. The combination of MorDalPhos with [Pd(π-cinnamyl)Cl]2 enables the amination of electron-rich, electron-neutral, and electron-poor aryl phosphates with a board range of aromatic, aliphatic, and heterocyclic amines. Common functional groups such as ether, keto, ester, and nitrile show an excellent compatibility in this reaction condition. The solvent-free amination reactions are also successful in both solid coupling partners. The gram-scale cross-coupling is achieved by this catalytic system.

Transient and Recyclable Halogenation Coupling (TRHC) for Isoflavonoid Synthesis with Site-Selective Arylation.

A transient and recyclable C-H iodination has been designed for the synthesis of isoflavonoids through the domino reactions of o-hydroxyphenyl enaminones and aryl boronic acids in the presence of catalytic KI and Pd catalyst. Instead of the conventional cross-coupling strategy employing pre-halogenated substrates, this method transforms raw C-H bond by means of a transient C-H halogenation to smoothly relay the subsequent C-arylation. Consequently, such a method avoids the pre-functionalization for C-halogen bond installation as well as the generation of stoichiometric halogen-containing waste following the cross-coupled product, disclosing an intriguing new coupling protocol to forge the C-C bond in the virgin area between classical C-X (X=halogen) bond cross coupling and the C-H activation.

Triflamides: Highly Reactive, Electronically Activated N-Sulfonyl Amides in Catalytic N-C(O) Amide Cross-Coupling.

The direct, highly chemoselective Suzuki-Miyaura cross-coupling of trifluoromethanesulfonamides (triflamides) by selective N-C(O) amide bond cleavage is reported. This operationally simple, mild, and user-friendly method accomplishes the direct synthesis of ketones from amides by a catalytic manifold as a powerful alternative to Weinreb amides. Mechanistic studies support rotational inversion and electronic activation, favoring selective insertion under mild conditions. Our data strongly suggest that triflamides should be routinely considered as precursors in amide bond cross-coupling.

Mechanism investigation for anoin-assisted nickel catalyzed C–F bond functionalization reaction: a DFT study

C–F bond functionalization still faces with great challenges in synthetic chemistry due to the inert nature of C–F bond in organic compounds. Herein, the newly reported DFT method M11-L was used to determine the mechanism of nickel catalyzed C–F/C–H bond cross coupling involving the C–F bond cleavage of flouroarenes and C–H bond functionalization of oxazoles. DFT calculations revealed that fluoride would stabilize the nickel(0) compound to afford an active nickel(0) ate-complex. With the assistance of fluoride, the oxidative addition of C–F bond to nickel(0) ate-complex would yield an active nickel(II) species, which is the rate-determining step in this catalytic cycle. The following C–H bond cleavage step would proceed via a direct deprotonation step under the attack of Bronsted base, to generate diarylnickel(II) species. Finally, reductive elimination step would occur to give the coupling product with regeneration of active nickel(0) ate-complex. In this pathway, we found that the relative free energies of nickel ate-complex species are more stable than commonly assumed neutral-nickel intermediates. This work could provide a new way for the mechanism study of inert C--F bond activation reactions.