Castro-Stephens coupling

The Castro-Stephens Coupling is a cross coupling reaction between a copper(I) acetylide and an aryl halide forming a disubstituted alkyne and a copper(I) halide.

The reaction was discovered in 1963 by University of California, Riverside chemists Castro and Stephens [1] [2] and is used as a tool in the organic synthesis of organic compounds. The reaction has similarities with the much older Rosenmund-von Braun synthesis (1916) between aryl halides and copper(I) cyanide and was itself modified in 1973 with as the Sonogashira coupling by adding a palladium catalyst and preparing the organocopper compound in situ, allowing copper to also be used catalytically.

A typical reaction is the coupling of iodobenzene with the copper acetylide of phenylacetylene in refluxing pyridine to diphenylacetylene:

Unlike the Sonogashira coupling, the Castro-Stephens coupling can produce heterocyclic compounds when a nucleophilic group is ortho to the aryl halide, although this typically requires use of DMF as solvent.[3][4]

References

  1. ^ The Substitution of Aryl Iodides with Cuprous Acetylides. A Synthesis of Tolanes and Heterocyclics R. D. Stephens and C. E. Castro J. Org. Chem.; 1963; 28(12); pp 3313 - 3315; doi:10.1021/jo01047a008
  2. ^ D. C. Owsley and C. E. Castro.Organic Syntheses, Coll. Vol. 6, p.916 (1988); Vol. 52, p.128 (1972) Link.
  3. ^ Synthesis of natural isocoumarins, artemidin and 3-propylisocoumarin G. Batu, R. Stevenson J. Org. Chem.; 1980; 45(8); pp 1532–1534; doi:10.1021/jo01296a044
  4. ^ Copper (I) Substitutions. Scope and Mechanism of Cuprous Acetylide Substitutions C. E. Castro, R. Havlin, V. K. Honwad, A. Malte, and Steve Moje J. Am. Chem. Soc.;1969; 91(23); pp 6464-6470; doi:10.1021/ja01051a049