Cuprates, which are organocopper reagents through the transmetallation of a copper salt with an organometallic (e.g. Grignard reagent, organozinc and organolithium), can often be generated and used in a stoichiometric manner, though catalytic versions have also since been developed. The exact composition of the cuprate depends on the mole ratio of the Grignard reagent (R-MgX) to the copper source (CuX). A 1:1 ratio will lead to the generation of RCu.MgX2, and if [R-MgX]:[CuX] is 2:1 instead, the resulting structure can be represented as R2CuMgX. The exact composition and structure of these cuprate species have always been controversial. Since a conclusive answer has not yet been found, the above chemical formula should treat as approximations in our discussion.
Another important observation is that, though the two cuprates are apparently generated from the same precursor reagents, they have demonstrated very different reactivities. RCu.MgX2, which is comparably less basic and less reactive, is more suitable for carbocupration – the carbometalation when the metal is copper. The reagent is also useful for displacement reactions which involve a stronger electrophile, such as an allylic halide.
R2CuMgX, which is more reactive, is useful for conjugate additions, and displacement reactions for less reactive electrophiles.
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| A carbocupration sequence. The ethylcopper is generated in-situ, and a carbocupration leads to the vinyl-copper intermediate. Iodination furnishes the final vinyl iodide product. |
A bit on the experimental aspect. The methodology to generate the cuprate and its subsequent reaction with a triple bond (alkyne) to give a vinyl-copper species is standard and can fit many different types of alkyne-containing substrates. The RCu.MgX2, for example, is often generated at low temperature (-35 oC) by dropwise addition of 1 equivalent of an ethereal solution of R-MgBr to 1 equivalent of copper salt (e.g. CuBr) in diethyl ether. Then, a suspension of RCu.MgX2, which often has a yellow to brown colour, is obtained. The cuprate reagent often has limited solubility in diethyl ether, thus resulting in the formation of a suspension.
To do the carbocupration, the cuprate solution is cooled down to -50 oC, and you add 1 equivalent of the alkyne substrate into the reaction mixture. The resulting mixture has to be warmed to effect complete formation of the vinyl-copper product, yet temperature control is absolutely essential here. The reaction will likely go wrong if you have warmed the reaction system to above -10 oC. At the end, you will afford to a vinyl-copper solution, which is often green in colour.
The formation of vinyl-copper suggests that the compound is now functionalized and activated for further useful reactions. A classic example is an iodine quench to generate the resulting vinyl iodide. The vinyl-copper can also be coupled with various electrophiles to generate heavily functionalized products. The vinyl iodide, on the other hand, is just as useful as a reaction precursor to install sp2-hybridized component in the final target compound.
by Ed Law
Reference:
1. '1,1-Dimetallic Reagents for the Elaboration of Stereoselectively Di- or Trisubstituted Linear
Substrates'
Jean F. Normant
Acc. Chem. Res., 2001, 34, 640-644.
2. 'Copper mediated carbometalation reactions'
D. S. Müller and I. Marek,
Chem. Soc. Rev., 2016, 45, 4552.
3. 'Stoichiometric versus Catalytic Use of Copper (I) Salts in the Synthetic Use of Main Group Organometallics'
Jean F. Normant
Pure & Appl. Chem., 1978, 50, 709—715.
