## 6 Palladium
### Sonogashira Coupling  
As for the Suzuki reaction, many methods already exist for performing the Sonogashira reaction using supported palladium catalysts. Much of the recent focus lies instead in adapting the copper-free version of this reaction to solid phase conditions. Copper can cause side reactions such as oxidative dimerization of the alkyne [49] and it is thus of interest to exclude the commonly used copper(I) iodide from the reaction protocol if possible. [PERSON] and co-workers investigated the use of bidentate NHC-palladium complexes (**26**, Scheme 18), attached to a core-shell polymeric support, in the copper-free Sonogashira reaction [50]. For electron-deficient aryl iodides, the use of cesium carbonate as the base at 60 \({}^{\circ}\)C was found to be the optimal, while for electron-rich aryl iodides, the conditions were changed somewhat, using piperidine at 100 \({}^{\circ}\)C instead. Yields were in all cases in the range of 90-95%. Two aryl bromides were also included in the study, as well as one aliphatic alkyne. These also afforded the desired product, although the aliphatic substrate required a longer reaction time and gave the product in a slightly lower yield (80%). [PERSON] and colleagues have reported a similar supported palladium-NHC complex for the Suzuki coupling of arenediazonium tetrafluoroborate salts with arylboronic acids, where the coupling reaction could be carried out at room temperature, using ethanol as the solvent [51].  
**Scheme 18.** A polymer-supported \(N\)-heterocyclic carbenes as ligand to palladium in the copper-free Sonogashira coupling of aryl iodides with aryl acetylenes.  
[PERSON] and colleagues applied the PS-PEG-tethered catalyst **17** [Scheme 15(a)], also applied for allylic sulfonylation, in the copper-free Sonogashira reaction under aqueous conditions [52]. The optimal base for most reactions was found to be triethylamine, although carboxy-substituted aliphatic terminal acetylenes fared better when cesium hydroxide was used instead. Aryl iodides as substrates in conjunction with phenyl acetylene as the alkyne in general gave high yields of coupling products under mild reaction conditions (40 \({}^{\circ}\)C), while aryl bromides required a higher reaction temperature to afford  
Figure 1: Supported catalysts developed for Suzuki reactions in water.  
product. Two aryl chlorides were also tested and gave product but in rather poor yields. The coupling of aliphatic carboxy-substituted alkynes was feasible, albeit in moderate yields.  
[PERSON] _et al_. prepared a palladium(0) diphenylphosphinoethane complex attached to a polystyrene support (**27**, Scheme 19) and applied this in the copper-free Sonogashira coupling with good results [53]. Various solvents and bases were screened, and running the reaction in neat piperidine at room temperature with 1 mol% **27** was found to be the best option. Both aromatic and aliphatic alkynes were investigated, while the aryl halide was limited to aromatic iodides. The same catalyst was subsequently used for coupling terminal alkynes with aromatic acid chlorides, using triethylamine as the combined base/solvent (Scheme 19) [54]. The possibility for recycling the catalyst were also studied and found to be good, with only a small drop in product yield after ten reaction cycles. Both types of coupling reactions were run under aerobic conditions.  
**Scheme 19.** Palladium-catalyzed coupling of aroyl chlorides with terminal alkynes.