The first organocopper compound, the explosive dicopper acetylide Cu2C2 was synthesized by Bottger in 1859. Henry Gilman prepared methylcopper in 1936. In 1941 Kharash discovered that reaction of a Grignard reagent with cyclohexenone in presence of Cu(I) resulted in 1,4-addition instead of 1,2-addition. In 1952 Gilman investigated for the first time dialkylcuprates.
Organocopper compounds are very reactive towards oxygen and water forming copper(I) oxide, tend to be thermally unstable and are generally insoluble in inert solvents. They are therefore difficult to handle and of little practical value. On the other hand organocopper reagents are used very frequently in organic chemistry as alkylating reagents prepared in situ in an inert environment with in general more functional group tolerance than corresponding Grignards or organolithium reagents. The electronegativity of copper is much higher than its next-door neighbour in the group 12 elements, zinc, suggesting less nucleophilicity for carbon.
Copper belongs to the group of coinage metals together with silver and gold and their chemistries have many similarities. The oxidation state can be +1 or +2 and intermediates can have oxidation state +3. Monovalent alkylcopper compounds (R-Cu) form divalent cuprates R2CuLi with organolithium compounds (R-Li) now known as Gilman reagents. Organocopper compounds can be stabilized with organophosphanes (R3P).
The cuprates have complex aggregation states in crystalline form and in solution. Lithium dimethylcuprate is a dimer in diethyl ether forming an 8-membered ring with two lithium atoms coordinating between two methyl groups.
The first ever crystal structure was determined in 1972 by Lappert for CuCH2SiMe3. 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 and pentafluorophenylcopper is a tetramer.
In many organometallic reactions involving copper, the reaction mechanism invokes a copper intermediate with oxidation state +3 for instance in reductive elimination processes to Cu(I). However Cu(III) compounds are rare in chemistry in general and until recently organocopper(III) species have been elusive. In 2007 the first spectroscopic evidence was obtained for the involvement of Cu(III) in the conjugate addition of the Gilman reagent to an enone :
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  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.
- Copper halides react with organolithium reagents to form the organocopper compound. Phenyl copper is prepared by reaction of phenyllithium with copper(I) bromide in diethyl ether.
- Reaction with a second equivalent of R-Li to R-Cu gives the lithium diorganocopper compound.
- Copper halides also react with Grignard reagents. The compound pentamesitylpentacopper is prepared from mesityl magnesium bromide and copper(I) chloride.
- Copper salts add to terminal alkynes to copper acetylides
- The copper metallocene (η-cyclopentadienyl triethylphosphine) copper can be prepared by reaction of copper(II) oxide with cyclopentadiene and triethylphosphine in pentane at reflux.
Organocopper reactions are classified in a number of reaction types:
- Substitution reactions of cuprates R2CuLi to alkyl halides R'-X gives the alkylcopper compound R'-Cu, the coupling product R-R and the lithium halide. The reaction mechanism is based on nucleophilic attack, namely oxidative addition of the alkyl halide to Cu(I) elevating it to a planar Cu(III) intermediate followed by reductive elimination. The nucleophilic attack is the rate-determining step. In the case for substitution of iodide, single electron transfer mechanism is proposed.
- Many electrophiles will do with an approximate order of reactivity acid chlorides > aldehydes > tosylates ~ epoxides > iodides > bromides > chlorides > ketones > esters > nitriles >> alkenes
- Oxidative coupling: 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: coupling reaction of aryl halides with copper metal (stoichometric) 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. At the same time a palladium catalyst converts an aryl bromide to the organopalladium intermediate (Ar'PdBr) and on transmetallation the biaryl is formed from ArPdAr'  .
- Redox neutral coupling: the coupling of terminal alkynes with halo-alkynes with a copper(I) salt in the Cadiot-Chodkiewicz coupling
- Thermal coupling of organocopper compounds
- Michael additions to enones where a Grignard would react in a 1,2-addition.. The mechanism goes through the nucleophilic attack of the alkyl group to form a RCu(III) intermediate. In the original paper describing this reaction methylmagnesium bromide is reacted with isophorone with and without 1 mole percent of added copper chloride :
- Addition of methylmagnesium bromide to isophorone Kharasch 1941
- Without added salt the main products are alcohol B (42%) from nucleophilic addition to the carbonyl group and diene C (48%) as its dehydration reaction product. With added salt the main product is 1,4-adduct A (82%) with some C (7%).
- Carbocupration is a nucleophilic addition of organocopper reagents (R-Cu) to acetylene or terminal alkynes resulting in an alkenylcopper compound (RC=C-Cu). The presence of magnesium(I) bromide is generally required. It is a special case of carbometalation.
- Chemistries of carbon with other elements of the periodic table:
|Core organic chemistry||many uses in chemistry.|
|Academic research, but no widespread use||Bond unknown / not assessed.|
- ↑ An introduction to synthesis using organocopper reagents Gary H Posner 1980 ISBN 0-471-69538-6
- ↑ Synthetic Methods of Organometallic and Inorganic Chemistry Vol 5, Copper, Silver, Gold, Zinc, Cadmium, and Mercury W.A. Herrmann Ed. ISBN 3-13-103061-5
- ↑ Organometallics Christoph Elschenbroich 3rd Ed. 2006 ISBN 3-527-29390-6 - Wiley-VCH, Weinheim
- ↑ Organic Syntheses, Coll. Vol. 6, p.875 (1988); Vol. 59, p.122 (1979) Link
- ↑ Rapid Injection NMR in Mechanistic Organocopper Chemistry. Preparation of the Elusive Copper(III) Intermediate Steven H. Bertz, Stephen Cope, Michael Murphy, Craig A. Ogle, and Brad J. Taylor J. Am. Chem. Soc.; 2007; 129(23) pp 7208 - 7209; (Communication) doi:10.1021/ja067533d
- ↑ Organocuprate Conjugate Addition: The Square-Planar "CuIII" Intermediate Haipeng Hu and James P. Snyder J. Am. Chem. Soc.; 2007; 129(23) pp 7210 - 7211;(Communication) doi:10.1021/ja0675346
- ↑ For an example see: Organic Syntheses, Coll. Vol. 6, p.248 (1988); Vol. 55, p.122 (1976) Link.
- ↑ Synthesis of Biaryls via Catalytic Decarboxylative Coupling Lukas J. Gooßen, et al. Science 313, 662 (2006) doi:10.1126/science.1128684
- ↑ Reagents: base potassium carbonate, solvent NMP, catalysts palladium acetylacetonate, Copper(I) iodide, MS stands for molecular sieves, ligand phenanthroline
- ↑ For an example: Organic Syntheses, Coll. Vol. 9, p.328 (1998); Vol. 72, p.135 (1995) Link.
- ↑ Eiichi Nakamura, Seiji Mori, Wherefore art thou Copper? Structures and Reaction Mechanisms of Organocuprate Clusters in Organic Chemistry, Angew. Chem. Int. Ed. 39, 3750-3771 (2000).
- ↑ Factors Determining the Course and Mechanisms of Grignard Reactions. II. The Effect of Metallic Compounds on the Reaction between Isophorone and Methylmagnesium bromide M. S. Kharasch, P. O. Tawney J. Am. Chem. Soc.; 1941; 63(9); 2308-2316. doi:10.1021/ja01854a005
- ↑ For an example: Organic Syntheses, Coll. Vol. 7, p.236 (1990); Vol. 64, p.1 (1986) Link
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