Hiyama Cross-Coupling Research Articles

Stereoselective Palladium-Catalyzed Hiyama Cross-Coupling Reaction of Tetrasubstituted gem-Difluoroalkenes.

We herein describe a diastereoselective Pd(0)-catalyzed Hiyama cross-coupling reaction of gem-difluoroalkenes. The use of organosilicon reagents in this reaction is advantageous over other organometallic reagents by allowing the introduction of a wide range of functional groups, including challenging alkyl groups. Also conveniently, the additive TBAF was not required for (hetero)aryl-substituted difluoroalkenes.

Computational and Experimental Design of the Octahedral PdFe Alloy Nanocatalyst for Hiyama Cross-Coupling and Environmental Pollutant Degradation

The research on various bimetallic nanoparticles (NPs) is rapidly expanding due to their widespread applications. However, the formation of bimetallic nanostructures in a facile way remains challenging. In the present study, an octahedral (Oh) PdFe alloy nanostructure was designed by following an aqueous medium synthesis strategy. Different metal precursor ratios were varied to observe the change in the shape and distribution of the Oh PdFe alloy nanostructure. Surprisingly, increasing the Fe content directed the finer growth of Oh morphology. However, increasing the Pd amount resulted in an uneven Oh PdFe alloy shape. The catalytic activity of the optimized Oh PdFe alloy was examined for Hiyama cross-coupling, and the degradation of dyes was scrutinized at different pH. The suggested alloy nanostructured catalyst exhibited improved catalytic behavior compared to other nanocatalysts, such as commercial catalyst Pd/C (95%), monometallic Pd Oh (98%), Fe NPs (15%), and PdFe NPs (85%), for the Hiyama cross-coupling reaction. The optimized alloy catalyst with less Pd and more Fe demonstrated 98% yield and excellent reusability up to the fifth consecutive cycle, conveying 80% yield. The stability of the Oh PdFe alloy nanocatalyst and the mechanistic aspects of Hiyama cross-coupling was supported by density functional theory. The degradation of both anionic dyes, Congo red, Eosin Y, and cationic rhodamine B, was performed under normal along with acidic and basic conditions. The degradation reaction was completed in an adequate time interval for all the dyes with no change in the morphology of the synthesized catalyst.

Magnetic nanoparticles embedded hexagonal boron nitride tethered N-heterocyclic carbene-palladium(II): An efficient and reusable magnetic catalyst for fluoride-free Hiyama cross-coupling and 4-nitrophenol reduction reactions

Heterogeneous catalysts have a wide range of applications on a commercial scale and are thus favored over their homogeneous analogs due to their stability and recyclability. However, their key drawback is poor reactivity. Consequently, the need to design heterogeneous catalysts with enhanced activity is a pressing matter. In this work, a new heterogeneous catalyst, magnetic nanoparticles embedded hexagonal boron nitride tethered N-heterocyclic carbene-palladium(II) (MNP-h-BN@NHC–Pd), was synthesized using a cost-effective and facile approach under aerobic conditions. The magnetic catalyst was characterized to confirm its structure, morphology, chemical composition, and thermal stability using various analytical techniques. The synthesized magnetic MNP-h-BN@NHC–Pd catalyst was studied in terms of its catalytic ability in the fluoride-free Hiyama cross-coupling reaction and recycled up to six cycles without any significant loss of activity. In addition, the catalytic application of the magnetic MNP-h-BN@NHC–Pd catalyst was further explored for the reduction of 4-nitrophenol (4-NP), a contaminant found in industrial wastewater, with a recyclability of up to nine cycles. The recovery of the magnetic MNP-h-BN@NHC–Pd catalyst from the reaction medium was achieved by use of an external magnetic field and the recycled magnetic catalyst did not show any drastic change in its chemical structure or morphology.

Transition Metal Catalyzed Hiyama Cross-Coupling: Recent Methodology Developments and Synthetic Applications

Hiyama cross-coupling is a versatile reaction in synthetic organic chemistry for the construction of carbon–carbon bonds. It involves the coupling of organosilicons with organic halides using transition metal catalysts in good yields and high enantioselectivities. In recent years, hectic progress has been made by researchers toward the synthesis of diversified natural products and pharmaceutical drugs using the Hiyama coupling reaction. This review emphasizes the recent synthetic developments and applications of Hiyama cross-coupling.

Direct Synthesis of Biphenyl-2-carbonitriles by Rh(III)-Catalyzed C-H Hiyama Cross-Coupling in Water.

This method represents an efficient rhodium(III)-catalyzed o-C-H arylation of readily available benzimidate derivatives with diverse arylsilanes in water as a sustainable solvent, enabling the straightforward synthesis of potentially useful biphenyl-2-carbonitrile derivatives. This silicon-based protocol employs benzimidates as both an efficacious directing group and the source of a nitrile group.

Copper-Promoted Hiyama Cross-Coupling of Arylsilanes With Thiuram Reagents: A Facile Synthesis of Aryl Dithiocarbamates.

We report herein a facile Hiyama cross-coupling reaction of arylsilanes with thiuram reagents (tetraalkylthiuram disulfides or tetraalkylthiuram monosulfide) enabled by copper fluoride. Compared to our previous work, this protocol is an alternative protocol for the generation of S-aryl dithiocarbamates. It features low toxic and readily available substrates, cost-effective promoter, easy performance, and provides good yields.

Palladium-catalyzed Hiyama cross-couplings of 2-chloro pyrimidines with organosilanes

Palladium-catalyzed Hiyama cross-couplings of 2-chloro pyrimidines with organosilanes

Palladium-catalyzed Hiyama cross-couplings of pyrimidin-2-yl tosylates with organosilanes

An efficient palladium-catalyzed Hiyama reaction between various pyrimidin-2-yl tosylates with organosilanes has been developed. The use of CuCl with TBAF as additive is essential for promotion of the construction of the carbon–carbon bond. This procedure shows wide functional group tolerance for electrophilic pyrimidin-2-yl tosylates and has been extended to aromatic amino-substituted pyrimidin-2-yl tosylates, affording the desired C2-aryl and alkenyl pyrimidine derivatives in good to excellent yields.

Design and synthesis of 3,3′-triazolyl biisoquinoline N,N’-dioxides via Hiyama cross-coupling of 4-trimethylsilyl-1,2,3-triazoles

A new strategy to effectively lock the conformation of substituents at the 3,3′-positions of axial-chiral biisoquinoline N,N’-dioxides was developed based on the strong dipole–dipole interaction between 1,2,3-triazole and pyridine N-oxide rings. The crystal structure and the DFT calculations of 3,3′-bis(1-benzyl-1H-1,2,3-triazole-4-yl)-1,1′-biisoquinoline N,N’-dioxide (3a) provided strong support for this strategy. Furthermore, we successfully demonstrated that readily available 4-trimethylsilyl-1,2,3-triazoles are viable nucleophiles for Hiyama cross-coupling.

Facile Approach to C-Glucosides by Using a Protecting-Group-Free Hiyama Cross-Coupling Reaction: High-Yielding Dapagliflozin Synthesis.

Access to unprotected (hetero)aryl pseudo-C-glucosides via a mild Pd-catalysed Hiyama cross-coupling reaction of protecting-group-free 1-diisopropylsilyl-d-glucal with various (hetero)aryl halides has been developed. In addition, selected unprotected pseudo-C-glucosides were stereoselectively converted into the corresponding α- and β-C-glucosides, as well as 2-deoxy-β-C-glucosides. This methodology was applied to the efficient and high-yielding synthesis of dapagliflozin, a medicament used to treat type 2 diabetes mellitus. Finally, the versatility of our methodology was proved by the synthesis of other analogues of dapagliflozin.

Dissecting Transmetalation Reactions at the Molecular Level: Role of the Coordinated Anion in Gas-Phase Models for the Transmetalation Step of the Hiyama Cross-Coupling Reaction

Palladium-catalyzed cross-coupling protocols have become a cornerstone in organic synthesis. Here, a gas-phase model of the Hiyama cross-coupling reaction was designed to shed light on the roles of coordinated anions (fluoride versus chloride) in transmetalation from Si to Pd. A combination of mass spectrometry experiments and DFT calculations was used. The ligated palladium fluoride and chloride cationic complexes, [(phen)Pd(X)]+ (X = F and Cl), readily react with vinyltrimethylsilane, Me3Si(CH═CH2), via transmetalation to give [(phen)Pd(CH═CH2)]+ as the major product. DFT calculations reveal that this transmetalation reaction is concerted and proceeds via a four-centered transition state, illustrating the role of coordinated halide in this gas-phase system. Two minor side products are observed corresponding to transmetalation to give [(phen)Pd(CH3)]+ and [(phen)Pd(SiMe2X)]+. DFT calculations suggest that these arise from the same initial Si to Pd methyl transmetalation pathway to give the [(phen)Pd(CH3) + Me2(CH═CH2)SiX]+ intermediate, which either then loses Me2(CH═CH2)SiX or reacts via C–C bond coupling to ultimately yield propene and [(phen)Pd(SiMe2X)]+. [(phen)Pd(CH═CH2)]+ undergoes a reaction with a second molecule of vinyltrimethylsilane to form an adduct, which upon collision-induced dissociation liberates 1,3-butadiene to form [(phen)Pd(SiMe3)]+. DFT calculations suggest a mechanism in which C–C bond formation is followed by migration of SiMe3 from C to Pd. Links between the observed gas-phase chemistry and solution-phase Pd-mediated homocoupling reactions of vinyltrimethylsilanes are explored.

Cross-Electrophile C(sp2 )-Si Coupling of Vinyl Chlorosilanes.

The cross-electrophile coupling has become a powerful tool for C-C bond formation, but its potential for forging the C-Si bond remains unexplored. Here we report a cross-electrophile Csp2 -Si coupling reaction of vinyl/aryl electrophiles with vinyl chlorosilanes. This new protocol offers an approach for facile and precise synthesis of organosilanes with high molecular diversity and complexity from readily available materials. The reaction proceeds under mild and non-basic conditions, demonstrating a high step economy, broad substrate scope, wide functionality tolerance, and easy scalability. The synthetic utility of the method is shown by its efficient accessing of silicon bioisosteres, the design of new BCB-monomers, and studies on the Hiyama cross-coupling of vinylsilane products.

Palladium-Catalyzed Amide N-C Hiyama Cross-Coupling: Synthesis of Ketones.

N-Acylglutarimides and arylsiloxanes reacted in the presence of Pd(OAc)2/PCy3, Et3N·3HF, and LiOAc to provide the corresponding arylketones in good yields. Aryl-, vinyl-, and alkyl-substituted N-acylglutarimides showed good activity in the coupling reactions of arylsiloxanes. The reaction had a broad substrate scope and showed good functional group tolerance. N-Benzoylsuccinimide and N-protected N-phenylbenzamides showed good activities in coupling reactions with phenylsiloxane. The employment of CuF2 as an activor afforded the decarbonylative products at 160 °C.

Stereoselective Synthesis of Cis- and Trans-Tetrasubstituted Vinyl Silanes Using a Silyl-Heck Strategy and Hiyama Conditions for Their Cross-Coupling.

We report a palladium-catalyzed, three-component carbosilylation reaction of internal symmetrical alkynes, silicon electrophiles, and primary alkyl zinc iodides. Depending on the choice of ligand, stereoselective synthesis of either cis- or trans-tetrasubstituted vinyl silanes is possible. We also demonstrate conditions for the Hiyama cross-coupling of these products to prepare geometrically defined tetrasubstituted alkenes.

Direct Hiyama Cross-Coupling of (Hetero)arylsilanes with C(sp2)–H Bonds Enabled by Cobalt Catalysis

We report a chelation-assisted C-H arylation of various indoles with sterically and electronically diverse (hetero)arylsilanes enabled by cost-effective Cp*-free cobalt catalysis. Key to the success of this strategy is the judicious choice of copper(II) fluoride as a bifunctional sliane activator and catalyst reoxidant. This methodology features a broad substrate scope and good functional group compatibility. The synthetic versatility of this protocol has been highlighted by the gram-scale synthesis and late-stage diversification of biologically active molecules.

Palladium-Catalyzed Hiyama Coupling of Benzylic Ammonium Salts via C-N Bond Cleavage.

The first palladium-catalyzed Hiyama cross-coupling of arylsilanes with benzyltrimethylammonium salts is reported. The reaction proceeds smoothly to facilitate C(sp2)-C(sp3) bond formation via cleavage of the C-N bond and provides a useful approach to various diarylmethanes with a broad substrate scope and excellent functional group tolerance in good to excellent yields.

Synthesis of Cyclic Alkenyl Dimethylsiloxanes from Alkynyl Benzyldimethylsilanes and Application in Polyene Synthesis.

Cyclic dimethylalkenylsiloxanes, useful motifs for (Z)-selective Hiyama cross-coupling, are accessed from alkynyl benzyldimethylsilanes featuring adjacent allylic or homoallylic oxygen substituents by semihydrogenation/debenzylation/cyclization. While formation of 5- and 6-membered rings can be achieved from the free alcohols using fluoride or silanolate, allylic acetate precursors to 5-membered rings display distinct modes of activation. The utility of these compounds is demonstrated through the preparation of a variety of (Z)-alkene-containing polyenes and application to a concise total synthesis of leukotriene B3.

SO2 conversion to sulfones: development and mechanistic insights of a sulfonylative Hiyama cross-coupling.

A Pd-catalyzed Hiyama cross-coupling reaction using SO2 is described. The use of silicon-based nucleophiles leads to the formation of allyl sulfones under mild conditions with a broad functional group tolerance. Control experiments coupled with DFT calculations shed light on the key steps of the reaction mechanism, revealing the crucial role of a transient sulfinate anion.

Synthesis of chiral \u03b1-trifluoromethyl alcohols and ethers via enantioselective Hiyama cross-couplings of bisfunctionalized electrophiles

Methods for synthesis of chiral organic compounds bearing trifluoromethyl-substituted stereocenters are of great interest for agrochemical and pharmaceutical labs and industries in their search for new bioactive materials. We report on employment of bisfunctionalized electrophiles, bearing both a trifluoromethyl and a functional group as direct substituents of the reactive center, in cross-coupling reactions. We exemplify this concept in the asymmetric synthesis of enantioenriched α-trifluoromethyl- and perfluoroalkyl-containing benzylic and allylic ethers and alcohols by nickel-catalyzed stereoconvergent Hiyama cross-coupling reaction. Substrate electrophiles are conveniently prepared in few steps from trifluoroacetic acid. The method represents a conceptually different approach to chiral CF3-substituted alcohols and ethers and allows for a rapid catalytic preparation of a wide range of these valuable compounds in high yields and enantioselectivity.

Green Synthesis of Palladium Nanoparticles: Applications in Aryl Halide Cyanation and Hiyama Cross-Coupling Reaction Under Ligand Free Conditions

In the current work, palladium nanoparticles (Pd NPs) were prepared from palladium acetate biogenically using the aqueous-ethanolic extract of black pepper (Piper nigrum) and characterized by various analytical techniques like XRD, FE-SEM, EDS, TEM, ATR-IR, UV–Vis spectroscopy, BET, TGA and ICP-OES analysis. The reduction of Pd(II) to Pd(0) is achieved by the action of various phytochemicals present in the black pepper extract like phenols, acids, pellitorine, ethyl piperonyl cyanoacetate, piperine and N-isobutyl-tetradeca-2,4-dienamide. The biosynthesized Pd NPs shown excellent catalytic activity in aryl halide cyanation and Hiyama cross-coupling reactions. Also, less toxic potassium hexacyanoferrate(II) trihydrate was used as cyanide source in aryl halide cyanation and Hiyama cross-coupling was performed under fluoride free condition. Both reactions proceeded well with Pd NPs under ligand free circumstances to give good to excellent yields. The Pd NPs were recovered after each reaction and recycled up to five times in aryl halide cyanation and ten times in Hiyama cross-coupling without considerable loss in the activity. Green synthesis of palladium nanoparticles: applications in aryl halide cyanation and Hiyama cross-coupling reaction under ligand free conditions.