Castro-Stephens-Sonogashira reaction

Cationic phosphine ligands containing guanidiniumphenyl moieties were originally developed in order to make use of their pronounced solubility in water [72, 73]. They were shown to form active catalytic systems in Pd-mediated C-C coupling reactions between aryl iodides and alkynes (Castro-Stephens-Sonogashira reaction) [72, 74] and Rh-catalyzed hydroformylation of olefins in aqueous two-phase systems [75]. 

The coupling of terminal alkynes with organic halides, known as the Castro-Stephens-Sonogashira reaction, has wide applications in synthesis. The most widely used method is the Sonogashira coupling, using a combination of palladium and copper as the catalyst.13 Recently,... 

Similar to the Sonogashira and related sp-sp couplings, there are no regio-or stereoselectivity complications in the Castro-Stephens coupling. Reaction conditions are quite vigorous, however, and where vinyl halides with defined geometry are used, the potential for olefin scrambling must be considered because there are rare cases where olefin isomerisation has been observed. ... 

Snieckus and his group members [104] used the known domino Sonogashira/ Castro-Stephens reaction [105, 106] for the synthesis of the natural product pli-cadin (6/1-209), this having been isolated from Psorelia plicata in 1991 [107]. In this synthesis, Pd°-catalyzed reaction of the alkyne 6/1-210 and the iodobenzene derivative 6/1-211 in the presence of Cul led to the furan 6/1-212, which was transformed into 6/1-209 via 6/1-213 (Scheme 6/1.54). There are some discrepancies of the physical data of the natural and the synthetic product thus, it might be possible that the natural product has a different structure. It should also be mentioned that the... 

Pd/Cu-catalyzed cross-coupling of organohalides with terminal alkynes. Cf. Cadiot-Chodkiewicz coupling and Castro-Stephens reaction. The Castro-Stephens coupling uses stoichiometric copper, whereas the Sonogashira variant uses catalytic palladium and copper. 

Although the authors call this reaction a Castro-Stephens reaction, they point out that it is really a Linstrumelle modification of the Sonogashira protocol. 

Castro-Stephens reaction Heck alkynylation Sonogashira alkynylating... 

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. 

This reaction is closely related to the Sonogashira Coupling, which uses a catalytic amount of palladium and copper, whereas the Castro-Stephens coupling uses a stoichiometric amount of copper. 

I 6 Arylation Reactions of Alh/nes The Sonogashira Reaction Castro-Stephens protocol... 

Inclusive reviews P. Cadiot, W. Chodkiewicz, Couplings of Acetylenes in Chemistry of Acetylenes, H. G. Viehe, Ed. (Marcel Dekker, New York, 1969) pp 597-647 K. Sonogashira, Comp. Org. Syn. 3, 551-561 (1991). Cf Castro-Stephens Coupling Ullmann Reaction. 

The Castro-Stephens reaction is the cross coupling of a copper acetylide (1) and an aryl or vinyl halide (2) to give a disubstituted alkyne (3). The reaction, which shares some common elements with the Sonogashira, Cadiot-Chodkiewicz, Rosenmund-von Braun, Hay, and Glaser coupling reactions, was discovered by Stephens and Castro in the early 1960s and has found some applications in synthesis. " ... 

One example where Castro-Stephens reaction proved to be superior to other methods is the synthesis of the binaphthyl compound 43. In this case, Sonogashira reaction on 42 afforded only an undesired helicene product, where the Castro-Stephens coupling with 4 gave the desired bis-alkyne 43 in 40% yield. Later a Negishi coupling approach was even more successful, delivering the same product in 90% yield. ... 

Compounds like tribenzocyclotriyne 47 are of interest because they have the ability to form conducting complexes with low-valent nickel by virtue of their planar, anti-aromatic character and cavity size. Youngs et al. published a synthesis of 47 where cyclotrimerization of precursor 48 is accomplished by S3mthesizing and then purifying the copper acetylide of the latter iodo alkyne and then refluxing said material in pyridine for 24 hours. In this way, the desired cyclotrimer 47 is obtained in an impressive 80% yield. The palladium-based Sonogashira reaction was attempted for this same substrate (48) and was much less effective (5% yield of 47). There are several examples where the Castro-Stephens approach was superior to other methods for creating cyclic arene/yne macrocycles. ... 

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