In organic chemistry, a Sonogashira coupling is a coupling reaction of terminal alkynes with aryl or vinyl halides. This reaction was first reported by Kenkichi Sonogashira and Nobue Hagihara in 1975.^[1] Organic chemistry is a specific discipline within chemistry which involves the scientific study of the structure, properties, composition, reactions, and preparation (by synthesis or by other means) of chemical compounds consisting of primarily carbon and hydrogen, which may contain any number of other elements, including nitrogen, oxygen, halogens as well... A coupling reaction in organic chemistry is a catch-all for a range of reactions in Organometallic chemistry where two hydrocarbon radicals are coupled with the aid of a metal containing catalyst. ... The structural formula of 2-butyne, a simple alkyne-containing molecule Alkynes are hydrocarbons that have at least one triple bond between two carbon atoms, with the formula CnH2n-2. ... In the context of organic molecules, aryl refers to any member of the set of functional groups or substituents that are derived from a simple aromatic ring. ... A vinyl halide in chemistry is any alkene with at least one halide substituent. ... Year 1975 (MCMLXXV) was a common year starting on Wednesday (link will display full calendar) of the Gregorian calendar. ...

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Catalyst

Typically, two catalysts are needed for this reaction: a zerovalent palladium complex and a halide salt of copper(I). The palladium complex activates the organic halides by oxidative addition into the carbon-halogen bond. Phosphine-palladium complexes such as tetrakis(triphenylphosphine)palladium(0) are used for this reaction, but palladium(II) complexes are also available because they are reduced to the palladium(0) species by the consumption of terminal alkynes in the reaction medium. In contrast, copper(I) halides react with the terminal alkyne and produce copper(I) acetylide, which acts as an activated species for the coupling reactions. It has been suggested that this article or section be merged into Catalysis. ... General Name, Symbol, Number palladium, Pd, 46 Chemical series transition metals Group, Period, Block 10, 5, d Appearance silvery white metallic Standard atomic weight 106. ... General Name, Symbol, Number copper, Cu, 29 Chemical series transition metals Group, Period, Block 11, 4, d Appearance metallic pinkish red Standard atomic weight 63. ... Oxidative addition and reductive elimination are two important classes of reactions in organometallic chemistry. ... General Name, Symbol, Number carbon, C, 6 Chemical series nonmetals Group, Period, Block 14, 2, p Appearance black (graphite) colorless (diamond) Standard atomic weight 12. ... The halogens or halogen elements are a series of nonmetal elements from Group 17 (old-style: VII or VIIA; Group 7 IUPAC Style) of the periodic table, comprising fluorine, F, chlorine, Cl, bromine, Br, iodine, I, and astatine, At. ... A chemical bond is the physical process responsible for the attractive interactions between atoms and molecules, and that which confers stability to diatomic and polyatomic chemical compounds. ... Phosphine is the common name for phosphorus hydride (PH3), also known by the IUPAC name phosphane and, occasionally, phosphamine. ... Tetrakis(triphenylphosphine)palladium(0) is the chemical compound Pd[P(C6H5)3]4, often abbreviated Pd(PPh3)4, or even PdP4. ... Copper(I) acetylide, or cuprous acetylide, is an inorganic chemical compound with the formula Cu2C2. ...

Conditions

The reaction medium must be basic to neutralize the hydrogen halide produced as the byproduct of this coupling reaction, so alkylamine compounds such as triethylamine and diethylamine are used as solvents. In addition, deaerated conditions are formally needed for Sonogashira coupling reactions because the palladium(0) complexes are unstable in the air, and oxygen promotes the formation of homocoupled acetylenes. Recently, development of air-stable organopalladium catalysts enable this reaction to be conducted in the ambient atmosphere. The general structure of an amine Amines are organic compounds and a type of functional group that contain nitrogen as the key atom. ... Triethylamine, also known as N,N-diethylethanamine, TEN or N,N,N-Triethylamine, is a colorless, volatile liquid with a strong, unpleasant and fishy smell reminiscent of ammonia. ... Diethylamine is a secondary amine with the molecular structure CH3CH2NHCH2CH3. ... A solvent is a liquid that dissolves a solid, liquid, or gaseous solute, resulting in a solution. ...

Mechanism

The Sonogashira coupling is a modification of the Castro-Stephens coupling with added palladium and in situ preparation of the copper acetylide. The reaction mechanism is not clearly understood but in the textbook mechanism revolves around a palladium cycle and a copper cycle.^[2] The Castro-Stephens Coupling is a cross coupling reaction between a Copper(I) acetylide and an aryl halide forming a disubstituted alkyne and a copper(I) halide. ... In situ is a Latin phrase meaning in the place. ... In chemistry, a reaction mechanism is the step by step sequence of elementary reactions by which overall chemical change occurs. ...

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• The active palladium catalyst is the 16 electron compound Pd(0)L₂ A which reacts with the aryl halide or triflate in an oxidative addition to Pd(II) complex B
• This complex reacts in a rate limiting transmetallation with the copper acetylide produced in the copper cycle to complex C expelling the copper halide CuX.
• Both organic ligands are trans oriented and convert to cis in a trans-cis isomerization to complex D
• In the final step the product is released in a reductive elimination with regeneration of Pd(0)

The copper cycle: Oxidative addition and reductive elimination are two important classes of reactions in organometallic chemistry. ... Transmetalation (alt. ... In chemistry, geometric isomerism is a form of stereoisomerism and describes the orientation of functional groups at the ends of a bond around which no rotation is possible. ... In chemistry, isomerization or isomerisation is the transformation of a molecule into a different isomer [1]. In some molecules and under some conditions, isomerisation occurs spontaneously. ... Oxidative addition and reductive elimination are two important classes of reactions in organometallic chemistry. ...

• The main limitation of this mechanism is its inability to account for deprotonation of a the terminal alkyne: The employed amines such as diethylamine or N,N-diisopropylethylamine are simply not basic enough. It is suggested that deprotonation is still possible after initial formation of a pi-alkyne complex E
• The organocopper compound F forms after reaction with the base and continues to react with palladium intermediate B with regeneration of copper halide.
• The copper acetylide is assumed to be involved in the reduction of Pd(II) catalysts, first forming a dialkyne-PdL₂ complex and then by reductive elimination Pd(0) and a diacetylene.
• A side reaction is a Glaser coupling of two acetylene units.
• Copper free reactions also exist making the reaction mechanism even more intractable. It is however reprted that palladium catalysts can be contaminated by copper salts.

Deprotonation is a chemistry term that refers to the removal of a proton (hydrogen ion H+) from a molecule, forming the conjugate base. ... Alkynes are hydrocarbons that have at least one triple bond between two carbon atoms. ... The general structure of an amine Amines are organic compounds and a type of functional group that contain nitrogen as the key atom. ... Diethylamine is a secondary amine with the molecular structure CH3CH2NHCH2CH3. ... N,N-Diisopropylethylamine, or Hünigs base, DIPEA or DIEA, is an organic compound and an amine. ... Organocopper compounds in organometallic chemistry contain carbon to copper chemical bonds. ... Oxidative addition and reductive elimination are two important classes of reactions in organometallic chemistry. ... Diacetylene is an unsaturated hydrocarbon with chemical formula HCCCCH. Categories: Stub ... The Cadiot-Chodkiewicz coupling in organic chemistry is a coupling reaction between a terminal alkyne and a haloalkyne catalyzed by a copper(I) salt such as copper(I) bromide and an amine base [1] [2]. The reaction product is a di-acetylene or di-alkyne. ...

Scope

Typical reagents and reaction conditions are copper(I) iodide, N,N-diisopropylethylamine, tetrakis(triphenylphosphine)palladium(0) and dimethylformamide,^[3] copper(I) iodide, diethylamine, dichlorobis(triphenylphosphine)palladium(II)^[4] or n-butylamine, copper(I) iodide, tetrakis(triphenylphosphine)palladium(0) and toluene as solvent^[5] The chemical compound copper(I) iodide has the formula CuI, more commonly known as cuprous iodide. ... N,N-Diisopropylethylamine, or Hünigs base, DIPEA or DIEA, is an organic compound and an amine. ... Tetrakis(triphenylphosphine)palladium(0) is the chemical compound Pd[P(C6H5)3]4, often abbreviated Pd(PPh3)4, or even PdP4. ... Dimethylformamide (DMF, N,N-dimethylformamide) is a clear liquid, miscible with water and majority of organic solvents. ... The chemical compound copper(I) iodide has the formula CuI, more commonly known as cuprous iodide. ... Diethylamine is a secondary amine with the molecular structure CH3CH2NHCH2CH3. ... The correct title of this article is . ... The chemical compound copper(I) iodide has the formula CuI, more commonly known as cuprous iodide. ... Tetrakis(triphenylphosphine)palladium(0) is the chemical compound Pd[P(C6H5)3]4, often abbreviated Pd(PPh3)4, or even PdP4. ... Toluene, also known as methylbenzene or phenylmethane is a clear, water-insoluble liquid with the typical smell of paint thinners, redolent of the sweet smell of the related compound benzene. ...

The Sonogashira coupling is applied in synthesis of cross-conjugated oligo(phenylene enynylene)s^[6] and phenanthroline derivatives.^[7] A chemically conjugated system, is a system of atoms covalently bonded with alternating single and double bonds (e. ... In chemistry, an oligomer consists of a finite number of monomer units (oligo is Greek for a few), in contrast to a polymer which, at least in principle, consists of an infinite number of monomers. ... In chemistry, the phenyl group or phenyl ring (often abbreviated as -Ph) is the functional group with the formula -C6H5 Picture where the six carbon atoms are arranged in a cyclic manner. ... The structural formula of 2-butyne, a simple alkyne-containing molecule Alkynes are hydrocarbons that have at least one triple bond between two carbon atoms, with the formula CnH2n-2. ... Phenanthroline is a heterocyclic organic compound. ...

References