The Stephens-Castro Reaction

To avoid the isolation of the relatively unstable and often explosive Cu acetyhde, a modification of the original Stephens-Castro protocol involving generation of the alkynylcopper species in situ from the corresponding terminal acetylene and Cul in DMSO (dimethyl sulfoxide) or DMF (N,N-dimethylformamide) has been developed (9). The Stephens-Castro reaction can also be performed at sub-mol% 

Cu loadings with a large excess of the N,N -dimethylethylenediamine (DMEDA) hgand that facilitates the formation of highly active monomeric Cu(I) acetylide species from the catalytically inactive copper acetyhde complexes [10]. 

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The reaction of aryl halides 1 with alkynylcopper(I) 2 under reflux in pyridine to prepare internal arylacetylenes is known as the Stephens-Castro reaction [Eq. (1)] [2]. The reaction has proved to be particularly important in the synthesis of a wide range of tolan and heteroaromatic alkynes [3]. Vinyl and allenic halides can also be used and several reviews... 

As described above (Section 5.2), the Stephens-Castro reaction of alkynylcopper with aryl and vinyl halides in boiling pyridine is a useful route to aryl and vinyl acetylenes. Direct cross-coupling of organic halides, such as sp halides, with terminal alkynes is a more convenient procedure. Such a reaction is not so easy, but it can be done using a Pd-complex catalyst [41]. Especially facile Pd-catalyzed cross-coupling of aryl and alkenyl halides with terminal alkynes proceeds smoothly under mild conditions in the presence of a cocatalyst of cuprous iodide in amine solvents [Eq. (28)] [42]. This methodology is now used widely for the constiuction of conjugated arylalkyne or enyne systems [43], as described below. It is attractive from a synthetic point of view because mild reaction conditions and simplicity of the procedure are associated with recent developments in modem acetylene chemistry [44]. 

In this variation of the Pd-catalyzed cross-coupling reaction, which is closely related to the Stephen-Castro reaction, copper acetylides are reacted with (hetero)aryl halides or triflates to produce (hetero)aryl alkynes [111]. The Sonogashira reaction is comparable to the Suzuki or Stille reactions in its scope and functional group tolerability. 

Alkynyl derivatives have been prepared by the Stephens-Castro reaction (Scheme 82). 3,5-Diiodo-4( 1H)-pyridinone without 0-protection is monocoupled with phenylethynylcopper. The 5-alkynyl product subsequently suffers Michael attack from the vicinal oxygen function to form a fused product, a furo[3,2-c]pyridine (355) [66JOC4071 87ACSA(B)219 89JCS(P1)1165]. 

The Stephens-Castro reaction generally requires heating in high-boiling solvents, but the reaction conditions can be substantially moderated by addition of a Pd-catalyst. Thus 2-iodopyridine is alkynylated (356) with phenylethynylcopper at room temperature with Pd-catalysis (82DOKU38). 

In the Stephens-Castro reaction 0-methylated 5-iodouracil has been reacted with THP-protected propargyl alcohol as a Cu-derivative to give the 5-alkynyl product (362). 

The reaction of aryl halides 29 with alkynylcoppers 30 is known as the Stephens-Castro reaction, which has proved to be particularly important in the synthesis of a wide... 

Processes similar to the Suzuki coupling reaction have been observed with alkynes. Thus, the Stephens-Castro reaction between unsaturated iodides (aryl, vinyl) and copper(l) acetylides in pyridine solvent results in the formation of new... 

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