Recently, a nickel-catalyzed Sonogashira coupling has been developed which allows for the coupling of non-activated alkyl halides to acetylene without the use of palladium, although a copper co-catalyst is still needed. It has also been reported that gold can be used as a heterogeneous catalyst, which was demonstrated in the coupling of phenylacetylene and iodobenzene with an Au/CeO catalyst. In this case, catalysis occurs heterogeneously on the Au nanoparticles, with Au(0) as the active site. Selectivity to the desirable cross coupling product was also found to be enhanced by supports such as CeO and LaO. Additionally, iron-catalyzed Sonogashira couplings have been investigated as relatively cheap and non-toxic alternatives to palladium. Here, FeCl is proposed to act as the transition-metal catalyst and CsCO as the base, thus theoretically proceeding through a palladium-free and copper-free mechanism.
While the copper-free mechanism has been shown to be viable, attempts to incorporate the various transition metals mentioned above as less expensive alternatives to palladium catalysts have shown a poor track record of success due to contamination of the reagents with trace amounts of palladium, suggesting that these theorized pathways are extremely unlikely, if not impossible, to achieve.
Studies have shown that organic and inorganic starting materials can also contain enough (ppb level) palladium for the coupling.