Castro–Stephens coupling

The Stephens - Castro coupling is an organic chemical name reaction. The reaction was discovered in 1963 by chemists Charles E. Castro and Robert D. Stephens. It developed today into a major synthesis tool in organic synthesis and combinatorial synthesis in medicinal chemistry.

The reaction is similar to the Rosenmund -von Braun reaction (1916 ), in which an aryl halide with copper ( I) cyanide reacts to acrylonitrile. Sonogashira - coupling ( 1975), in which the copper acetylide is prepared in situ and the cross-coupling is carried out with a palladium catalyst is to be regarded as a further development of Stephens - Castro- coupling.

The Stephens -Castro coupling is carried out by reacting the Kupferacetylides with an aryl halide in the presence of pyridine. This is caused by formation of a carbon -carbon bond, an aromatic alkyne.

Reaction mechanism

The course of the reaction starts from the terminal alkyne. It is first associated with the copper (I ) ion by forming a π - complex. He said this caused considerable electron deficiency at the alkyne of the pKa value of about 30 is lowered to below 9. Through this activation, the alkyne can be deprotonated in the next step; For this purpose, pyridine is used. Simultaneously, a copper (I) organic compound to which is added the aryl iodide is oxidatively. The thus formed, little stable copper ( III) compound decomposes in a fast subsequent step by reductive elimination to Arylalkin and copper (I ) iodide, which is the association of a new terminal alkyne available. In this manner the catalyst is restored.

Disadvantages

The disadvantage of the Stephens -Castro coupling consists in the amounts produced in stoichiometric amounts thereby potentially explosive atmospheres are copper acetylides. Another disadvantage of the use of boiling pyridine is to be considered. For these reasons, the Sonogashira coupling, the Stille coupling or similar reactions are preferably used therefore nowadays.