Organocopper compounds is the chemistry of organometallic compounds containing a carbon to copper chemical bond. Organocopper chemistry is the study of organocopper compounds describing their physical properties, synthesis and reactions. [1] [2] [3] They are reagents in organic chemistry.
The first organocopper compound, the explosive copper(I) acetylide Cu2C2 (Cu−C≡C−Cu), was synthesized by Rudolf Christian Böttger in 1859 by passing acetylene gas through a solution of copper(I) chloride: [4]
Organocopper compounds are diverse in structure and reactivity, but organocopper compounds are largely limited in oxidation states to copper(I), sometimes denoted Cu+. As a d10 metal center, it is related to Ni(0), but owing to its higher oxidation state, it engages in less pi-backbonding. Organic derivatives of Cu(II) and Cu(III) are invoked as intermediates but rarely isolated or even observed. In terms of geometry, copper(I) adopts symmetrical structures, in keeping with its spherical electronic shell. Typically one of three coordination geometries is adopted: linear 2-coordinate, trigonal 3-coordinate, and tetrahedral 4-coordinate. Organocopper compounds form complexes with a variety of soft ligands such as alkylphosphines (R3P), thioethers (R2S), and cyanide (CN−).
Copper(I) salts have long been known to bind CO, albeit weakly. A representative complex is CuCl(CO), which is polymeric. In contrast to classical metal carbonyls, pi-backbonding is not strong in these compounds. [5]
Alkenes bind to copper(I), although again generally weakly. The binding of ethylene to Cu in proteins is of broad significance in plant biology so much so that ethylene is classified as a plant hormone. Its presence, detected by the Cu-protein, affects ripening and many other developments. [6]
Although copper does not form a metallocene, half-sandwich complexes can be produced. One such derivative is π-cyclopentadienyl(triethylphosphine)copper(I). [7]
Copper halides react with organolithium reagents to give organocopper compounds. The area was pioneered by Henry Gilman, who reported methylcopper in 1936. Thus, phenylcopper is prepared by reaction of phenyllithium with copper(I) bromide in diethyl ether. Grignard reagents can be used in place of organolithium compounds. Gilman also investigated the dialkylcuprates. These are obtained by combining two equivalent of RLi with Cu(I) salts. Alternatively, these cuprates are prepared from oligomeric neutral organocopper compounds by treatment with one equivalent of organolithium reagent.
Compounds of the type [CuRn](n-1)- are reactive towards oxygen and water, forming copper(I) oxide. They also tend to be thermally unstable, which can be useful in certain coupling reactions. Despite or because of these difficulties, organocopper reagents are frequently generated and consumed in situ with no attempt to isolate them. They are used in organic synthesis as alkylating reagents because they exhibit greater functional group tolerance than corresponding Grignard and organolithium reagents. The electronegativity of copper is much higher than its next-door neighbor in the group 12 elements, zinc, suggesting diminished nucleophilicity for its carbon ligands.
Copper salts react with terminal alkynes to form the acetylides.
Alkyl halides react with organocopper compounds with inversion of configuration. On the other hand, reactions of organocopper compound with alkenyl halides proceed with retention of subtrate’s configuration. [8]
Organocopper compounds couple with aryl halides:
Alkyl and aryl copper complexes aggregate both in crystalline form and in solution. Aggregation is especially evident for charge-neutral organocopper compounds, i.e. species with the empirical formula (RCu), which adopt cyclic structures. Since each copper center requires at least two ligands, the organic group is a bridging ligand. This effect is illustrated by the structure of mesitylcopper, which is a pentamer. A cyclic structure is also seen for CuCH2SiMe3, first 1:1 organocopper compound to be analyzed by X-ray crystallography (1972 by Lappert). This compound is relatively stable because the bulky trimethylsilyl groups provide steric protection. It is a tetramer, forming an 8-membered ring with alternating Cu-C bonds. In addition the four copper atoms form a planar Cu4 ring based on three-center two-electron bonds. The copper to copper bond length is 242 pm compared to 256 pm in bulk copper. In pentamesitylpentacopper a 5-membered copper ring is formed, similar to (2,4,6-trimethylphenyl)gold, and pentafluorophenylcopper is a tetramer. [9]
Lithium dimethylcuprate is a dimer in diethyl ether, forming an 8-membered ring with two lithium atoms linking two methyl groups. Similarly, lithium diphenylcuprate forms a dimeric etherate, [{Li(OEt2)}(CuPh2)]2, in the solid state. [10]
The involvement of the otherwise rare Cu(III) oxidation state has been demonstrated in the conjugate addition of the Gilman reagent to an enone: [11] In a so-called rapid-injection NMR experiment at -100 °C, the Gilman reagent Me2CuLi (stabilized by lithium iodide) was introduced to cyclohexenone (1) enabling the detection of the copper — alkene pi complex 2. On subsequent addition of trimethylsilyl cyanide the Cu(III) species 3 is formed (indefinitely stable at that temperature) and on increasing the temperature to -80 °C the conjugate addition product 4. According to an accompanying in silico experiments [12] the Cu(III) intermediate has a square planar molecular geometry with the cyano group in cis orientation with respect to the cyclohexenyl methine group and anti-parallel to the methine proton. With other ligands than the cyano group this study predicts room temperature stable Cu(III) compounds.
Prior to the development of palladium-catalyzed cross coupling reactions, copper was the preferred catalyst for almost a century. Palladium offers a faster, more selective reaction. However, in recent years copper has reemerged as a synthetically useful metal, because of its lower cost and because it is an eco-friendly metal. [13]
Reactions of R2CuLi with alkyl halides R'-X give the coupling product:
The reaction mechanism involves oxidative addition (OA) of the alkyl halide to Cu(I), forming a planar Cu(III) intermediate, followed by reductive elimination (RE). The nucleophilic attack is the rate-determining step. In the substitution of iodide, a single-electron transfer mechanism is proposed (see figure).
Many electrophiles participate in this reaction. The approximate order of reactivity, beginning with the most reactive, is as follows: acid chlorides [14] > aldehydes > tosylates ~ epoxides > iodides > bromides > chlorides > ketones > esters > nitriles >> alkenes
Generally the OA-RE mechanism is analogous to that of palladium-catalyzed cross coupling reactions. One difference between copper and palladium is that copper can undergo single-electron transfer processes. [8]
Oxidative coupling is the coupling of copper acetylides to conjugated alkynes in the Glaser coupling (for example in the synthesis of cyclooctadecanonaene) or to aryl halides in the Castro-Stephens Coupling.
Reductive coupling is a coupling reaction of aryl halides with a stoichiometric equivalent of copper metal that occurs in the Ullmann reaction. In an example of a present-day cross coupling reaction called decarboxylative coupling, a catalytic amount of Cu(I) displaces a carboxyl group forming the arylcopper (ArCu) intermediate. Simultaneously, a palladium catalyst converts an aryl bromide to the organopalladium intermediate (Ar'PdBr), and on transmetallation the biaryl is formed from ArPdAr'. [15] [16]
Redox neutral coupling is the coupling of terminal alkynes with halo-alkynes with a copper(I) salt in the Cadiot-Chodkiewicz coupling. Thermal coupling of two organocopper compounds is also possible.
Carbocupration is a nucleophilic addition of organocopper reagents (R-Cu) to acetylene or terminal alkynes resulting in an alkenylcopper compound (RC=C−Cu). [17] It is a special case of carbometalation and also called the Normant reaction. [18]
Copper hydrides are specialized reagents used occasionally as reducing agent. The best known copper hydride is called Stryker's reagent, a cluster compound with the formula [(PPh3)CuH]6. It reduces the alkene α,β-unsaturated carbonyl compounds. [20]
The Buchwald reaction is a copper-catalyzed asymmetric reduction of activated alkenes. The reagent is generated in situ from copper(I) NHC complex. The hydride equivalents are provided by a silane. [21] [22]
Synthesis of Z-Fluoro alkene dipeptide isosteres,. [23] [24] Other effort to make this a more selective reactions includes the use of oxidation reduction condition for the reaction. [25] Fluoride acts as a leaving group and it enhances regioselectivity in the transformation the Z- fluoroalkene.
Generally, the alkylation reaction of organocopper reagents proceed via gamma- alkylation. Cis- gamma attack occurs better in cyclohexyl carbamate due to sterics. The reaction is reported to be favorable in ethereal solvents. This method was proved to be very effective for the oxidative coupling of amines and alkyl, including tertbutyl, and aryl halides. [26]
Vicinal functionalization using a Carbocupration- Mukaiyama aldol reaction sequence: [27]
Muller and collaborators reported a vicinal functionalization of α,β- acetylenic esters using a carbocupration/Mukaiyama aldol reaction sequence (as shown in fig. above) carbocupration favors the formation of the Z- aldol.
In organic chemistry, an alkyne is an unsaturated hydrocarbon containing at least one carbon—carbon triple bond. The simplest acyclic alkynes with only one triple bond and no other functional groups form a homologous series with the general chemical formula CnH2n-2. Alkynes are traditionally known as acetylenes, although the name acetylene also refers specifically to C2H2, known formally as ethyne using IUPAC nomenclature. Like other hydrocarbons, alkynes are generally hydrophobic.
A Gilman reagent is a lithium and copper (diorganocopper) reagent compound, R2CuLi, where R is an alkyl or aryl. These reagents are useful because, unlike related Grignard reagents and organolithium reagents, they react with organic halides to replace the halide group with an R group (the Corey–House reaction). Such displacement reactions allow for the synthesis of complex products from simple building blocks.
Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene. Alkylating agents are reagents for effecting alkylation. Alkyl groups can also be removed in a process known as dealkylation. Alkylating agents are often classified according to their nucleophilic or electrophilic character.
The Stille reaction is a chemical reaction widely used in organic synthesis. The reaction involves the coupling of two organic groups, one of which is carried as an organotin compound. A variety of organic electrophiles provide the other coupling partner. The Stille reaction is one of many palladium-catalyzed coupling reactions.
The Suzuki reaction is an organic reaction, classified as a cross-coupling reaction, where the coupling partners are a boronic acid and an organohalide and the catalyst is a palladium(0) complex. It was first published in 1979 by Akira Suzuki, and he shared the 2010 Nobel Prize in Chemistry with Richard F. Heck and Ei-ichi Negishi for their contribution to the discovery and development of palladium-catalyzed cross-couplings in organic synthesis. This reaction is also known as the Suzuki–Miyaura reaction or simply as the Suzuki coupling. It is widely used to synthesize polyolefins, styrenes, and substituted biphenyls. Several reviews have been published describing advancements and the development of the Suzuki reaction. The general scheme for the Suzuki reaction is shown below, where a carbon-carbon single bond is formed by coupling a halide (R1-X) with an organoboron species (R2-BY2) using a palladium catalyst and a base.
The Sonogashira reaction is a cross-coupling reaction used in organic synthesis to form carbon–carbon bonds. It employs a palladium catalyst as well as copper co-catalyst to form a carbon–carbon bond between a terminal alkyne and an aryl or vinyl halide.
Organopalladium chemistry is a branch of organometallic chemistry that deals with organic palladium compounds and their reactions. Palladium is often used as a catalyst in the reduction of alkenes and alkynes with hydrogen. This process involves the formation of a palladium-carbon covalent bond. Palladium is also prominent in carbon-carbon coupling reactions, as demonstrated in tandem reactions.
Organoborane or organoboron compounds are chemical compounds of boron and carbon that are organic derivatives of BH3, for example trialkyl boranes. Organoboron chemistry or organoborane chemistry is the chemistry of these compounds.
The Bamford–Stevens reaction is a chemical reaction whereby treatment of tosylhydrazones with strong base gives alkenes. It is named for the British chemist William Randall Bamford and the Scottish chemist Thomas Stevens Stevens (1900–2000). The usage of aprotic solvents gives predominantly Z-alkenes, while protic solvent gives a mixture of E- and Z-alkenes. As an alkene-generating transformation, the Bamford–Stevens reaction has broad utility in synthetic methodology and complex molecule synthesis.
The Hiyama coupling is a palladium-catalyzed cross-coupling reaction of organosilanes with organic halides used in organic chemistry to form carbon–carbon bonds. This reaction was discovered in 1988 by Tamejiro Hiyama and Yasuo Hatanaka as a method to form carbon-carbon bonds synthetically with chemo- and regioselectivity. The Hiyama coupling has been applied to the synthesis of various natural products.
The Corey–House synthesis is an organic reaction that involves the reaction of a lithium diorganylcuprate with an organic pseudohalide to form a new alkane, as well as an ill-defined organocopper species and lithium halide as byproducts.
The Ullmann reaction or Ullmann coupling is a coupling reaction between aryl halides. Traditionally this reaction is effected by copper, but palladium and nickel are also effective catalysts. The reaction is named after Fritz Ullmann.
A Grignard reagent or Grignard compound is a chemical compound with the general formula R−Mg−X, where X is a halogen and R is an organic group, normally an alkyl or aryl. Two typical examples are methylmagnesium chloride Cl−Mg−CH3 and phenylmagnesium bromide (C6H5)−Mg−Br. They are a subclass of the organomagnesium compounds.
The Negishi coupling is a widely employed transition metal catalyzed cross-coupling reaction. The reaction couples organic halides or triflates with organozinc compounds, forming carbon-carbon bonds (C-C) in the process. A palladium (0) species is generally utilized as the metal catalyst, though nickel is sometimes used. A variety of nickel catalysts in either Ni0 or NiII oxidation state can be employed in Negishi cross couplings such as Ni(PPh3)4, Ni(acac)2, Ni(COD)2 etc.
Organozinc compounds in organic chemistry contain carbon (C) to zinc (Zn) chemical bonds. Organozinc chemistry is the science of organozinc compounds describing their physical properties, synthesis and reactions.
The Castro–Stephens coupling is a cross coupling reaction between a copper(I) acetylide and an aryl halide in pyridine, forming a disubstituted alkyne and a copper(I) halide.
The Glaser coupling is a type of coupling reaction. It is by far the oldest acetylenic coupling and is based on cuprous salts like copper(I) chloride or copper(I) bromide and an additional oxidant like oxygen. The base in its original scope is ammonia. The solvent is water or an alcohol. The reaction was first reported by Carl Andreas Glaser in 1869. He suggested the following process for his way to diphenylbutadiyne:
Organobismuth chemistry is the chemistry of organometallic compounds containing a carbon to bismuth chemical bond. Applications are few. The main bismuth oxidation states are Bi(III) and Bi(V) as in all higher group 15 elements. The energy of a bond to carbon in this group decreases in the order P > As > Sb > Bi. The first reported use of bismuth in organic chemistry was in oxidation of alcohols by Challenger in 1934 (using Ph3Bi(OH)2). Knowledge about methylated species of bismuth in environmental and biological media is limited.
Reactions of organocopper reagents involve species containing copper-carbon bonds acting as nucleophiles in the presence of organic electrophiles. Organocopper reagents are now commonly used in organic synthesis as mild, selective nucleophiles for substitution and conjugate addition reactions.
Decarboxylative cross coupling reactions are chemical reactions in which a carboxylic acid is reacted with an organic halide to form a new carbon-carbon bond, concomitant with loss of CO2. Aryl and alkyl halides participate. Metal catalyst, base, and oxidant are required.