Copper acetylides, cross-coupling with

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. 

The Pd-catalyzed coupling of o-haloanilines and terminal alkynes tends to produce either the 2-(l-alkynyl)aniline or mixtures of the alkynylanilines and the corresponding indoles [17,18]. However, iV-benzyl-2-iodoaniline has recently been cross-coupled with terminal alkynes to afford the corresponding ben-zylindoles using a Pd zeolite catalyst (Eq. 14) [39]. One can also employ stoichiometric amounts of copper acetylides to effect this transformation [22-24]. 

Thus, the cross-coupling of different iodo-A -methylpyrazolecarboxylic acids with copper acetylides leads to closure of the six-membered ring. 

AUenynes. An attractive route to allenynes involves the reaction of allcnic bromides with 1-alkynes in the presence of catalytic amounts of this Pd(0) complex and Cul in diethylamine at 25° (equation 1). The synthesis presumably involves cross-coupling between an allenic palladium cr-compound and a copper acetylide. 

The mechanism of the Sonogashira cross-coupling follows the expected oxidative addition-reductive elimination pathway. However, the structure of the catalytically active species and the precise role of the Cul catalyst is unknown. The reaction commences with the generation of a coordinatively unsaturated Pd species from a Pd " complex by reduction with the alkyne substrate or with an added phosphine ligand. The Pd " then undergoes oxidative addition with the aryl or vinyl halide followed by transmetallation by the copper(l)-acetylide. Reductive elimination affords the coupled product and the regeneration of the catalyst completes the catalytic cycle. 

In another copper-catalyzed reaction, cross-coupling of alkynes with phosphi-ne-boranes was followed by surprising oxidation to yield ketones (Scheme 69) [122]. The active species was proposed to be a copper phosphido-borane complex, formed by proton transfer to a Cu-OH group. Formation of a Cu-acetylide followed by P-C reductive elimination would then yield a phosphino-alkyne, whose subsequent Cu-mediated air oxidation yields the ketone. 

For the copper-free Sonogashira reaction, the mechanistic study reported in this thesis revealed that, just like in other cross-coupling reactions (i.e. Stille, Negishi), there are several competing reaction pathways and a change on the reaction conditions (e.g. solvent, ligands, substrates, base) might favor one over the other ones. Moreover, a new mechanism in which the acetylide (formed by deprotonation of the alkyne) directly reacts with the catalyst was also proposed. 

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. " ... 

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