Organic copper compounds are compounds contain carbon-copper bonds in organometallic chemistry. Copper is one of the oldest transition metals to be used in synthetic organic chemistry and organocopper reagents has become one of the most popular synthetic tools in the synthesis of natural product. The unique properties of organocopper compounds make them unavoidable reagents for the conjugate addition and other important reactions.
Applications
Cross-coupling reaction: Copper has been the preferred choice for catalyzing cross-coupling reactions nearly a century before the development of palladium catalysts. Palladium provides faster, more selective reactions. However, in recent years copper has reappeared as a useful synthetic metal because it is an environmentally friendly metal and its cost is low. The cross-coupling reaction mechanism involves the oxidative addition of alkyl halides to Cu (I) to form planar Cu (III) intermediates, followed by reductive elimination. Nucleophilic attack is the rate-determining step. In the substitution of iodide, a single electron transfer mechanism has been proposed (Fig.1).
Coupling reaction: Oxidative coupling is the coupling of copper acetylides to conjugated alkynes in the Glaser coupling or to aryl halides in the Castro-Stephens Coupling. Reductive coupling is the coupling reaction of aryl halide with a stoichiometric equivalent of copper metal that occurs in the Ullmann reaction. In the decarboxylation coupling, a catalytic amount of Cu (I) displaces the carboxyl group and forms an aryl copper (ArCu) intermediate. At the same time, palladium catalysts convert aryl bromides into organic palladium intermediates (Ar'PdBr) and then ArPdAr’ forms. Sonogashira cross-coupling reaction is the typical example using organocopper compounds as catalysts. The Sonogashira cross-coupling reaction is a cross-coupling reaction to form carbon-carbon bonds in organic synthesis. Sonogashira cross-coupling reaction is employed in a wide variety of areas because of its usefulness in the formation of carbon–carbon bonds. The reaction can be carried out under mild conditions, such as at room temperature, in aqueous media, or with a mild base, which allows the use of the Sonogashira cross-coupling reaction in the synthesis of complex molecules. Its applications include in the production of natural products, organic materials, pharmaceuticals, and nanomaterials.
Conjugate addition: When Grignard reagents are added to cyclohexenone in the presence of Cu (I), resulting in 1,4-addition instead of 1,2-addition, which heralds extensive research on the conjugate additions to enones with organocuprates. If a Grignard reagent is used, the reaction with enones would proceed via 1,2-addition. The mechanism of copper (II) 1,4-addition is to form Cu (III) intermediates by nucleophilic addition of Cu (I) species at the β-carbon of the alkene, followed by reduction eliminate of Cu (I).
Fig.1. The cross-coupling reaction mechanism.
