CASTRO-STEPHENS COUPLING Reporter: Xiong Rui Supervisor: Fanyang Mo Date: 20/5/2016

Outline 1.Background 2. Mechanism 3.Synthetic Applications 4.Conclusion

Background The copper(I) mediated coupling of aryl or vinyl halides with aryl- or alkyl-substituted alkynes is known as the Castro-Stephens coupling. In the early 1960s, R.D. Stephens and C.E. Castro discovered that disubstituted (diaryl or arylalkyl) acetylenes were produced in good yield upon treatment of aryl iodides with stoichiometric amounts of copper(I) acetylides under a nitrogen atmosphere in refluxing pyridine.

Background The best results are obtained with electron-poor aryl halides. When aryl iodides bear a nucleophilic substituent in the ortho position, cyclization to the corresponding heterocycles occurs exclusively .

Mechanism The reaction is believed to proceed via a four-centered transition state.

Synthetic Applications In the laboratory of M. Nilsson, a facile one-pot synthesis of isocumestans (6H-benzofuro[2,3-c][1]benzopyran-6-ones) was developed via a novel extension of the Castro-Stephens coupling utilizing ortho-iodophenols and ethyl propiolate. The reaction can be regarded as an extended Castro-Stephens coupling where an intermediate cuprated benzofuran couples with a second equivalent of ortho-iodophenol, and the product lactonizes to isocumestan.

Synthetic Applications

Synthetic Applications

Conclusion Most copper(I) salts are insoluble in organic solvents,so the reaction are often heterogeneous and require high reaction temperature. The reactions are sensitive to functional groups on the aryl halides,and the yields are often irreproducible.

Thank you!