## Results and Discussion
### Synthesis of Liquid-Phase Phosphine Reagent (2)
#### Poly(ethylene glycol) as a Soluble Polymer Matrix for the Stille Cross Coupling Reaction
\begin{table}
\begin{tabular}{c c c c c c c c c} \hline
**Entry** & **Catalyst** & **Solvent** & **conc./mM\({}^{a}\)** & _T/\({}^{c}\)C** & **LiCl** & **Time/h** & **Yield 18a/\%\({}^{b}\) Yield 19a/\%\({}^{b}\)** \\ \hline
1 & Pd(PPh\({}_{3}\))\({}_{2}\)Cl\({}_{2}\) & toluene & 20 & 110 & + & 24 & 22 & _\({}^{c}\)_ \\
2 & Pd(PPh\({}_{3}\))\({}_{2}\)Cl\({}_{2}\) & THF & 20 & reflux & + & 24 & 68 & _\({}^{c}\)_ \\
3 & Pd(PPh\({}_{3}\))\({}_{2}\)Cl\({}_{2}\) & DMF & 20 & 80 & + & 24 & 89 & _\({}^{c}\)_ \\
4 & Pd(PPh\({}_{3}\))\({}_{4}\) & toluene & 20 & 110 & + & 24 & 53 & _\({}^{c}\)_ \\
5 & Pd(PPh\({}_{3}\))\({}_{4}\) & THF & 20 & reflux & + & 24 & 7 & 73 \\
6 & Pd(PPh\({}_{3}\))\({}_{4}\) & DMF & 20 & 80 & + & 24 & 10 & 58 \\
7 & Pd(PPh\({}_{3}\))\({}_{2}\)Cl\({}_{2}\) & DMF & 20 & 80 & - & 24 & 86 & 12 \\
8 & Pd(PPh\({}_{3}\))\({}_{2}\)Cl\({}_{2}\) & DMF & 20 & 80 & + & 48 & 97 & 0 \\
9 & Pd(PPh\({}_{3}\))\({}_{2}\)Cl\({}_{2}\) & DMF & 10 & 80 & + & 24 & 98 & 0 \\ \hline \end{tabular} \({}^{a}\) Based on the concentration of PEG-bound substrate **15a**.  
\({}^{b}\) Isolated yields after workup.  
\({}^{c}\) Not determined.  
\end{table} 
Table 4: Optimization of the Stille cross-coupling reaction parameters between **15a** and **16**. The efficiency of the initial series of experiments was determined both by \({}^{1}\)H NMR analysis of the PEG-biaryl adduct **17a** and, following transesterification, by the isolated yields of the biaryl methyl ester **18a** and monoaryl ester **19a** (resulting from no cross-coupling with **15a**). Reactions were conducted in toluene, THF or DMF, with either a Pd(0) or Pd(II) catalyst (0.1 equiv.) in the presence or absence of LiCl (10 equiv.). A three-fold excess of tributyl phenylstannane **16** was used relative to the PEG-supported electrophile **15a**. Additional parameters that were modified included temperature, reaction time and reaction concentration. solvent (Table 1, entries 3 and 6-9) under standard conditions of **15a** (20 mM) and 80\({}^{\circ}\)C. The results show that DMF is the most superior of the solvents tested for the PEG-supported Stille reaction. Similar to the case with THF, PdCl\({}_{2}\)(PPh\({}_{3}\))\({}_{2}\) is the best catalyst (Table 4, entries 3 and 6) with considerable amounts of the transesterified iodide **19a** being recovered after reaction with Pd(0) (58%). In addition, by leaving the reaction to run for 48 h rather than the preliminary 24 h, a considerable increase in the observed biaryl adduct **18a** is achieved (89 and 97% respectively) (Table 4, entries 3 and 8). In a recent fluorous-phase approach to the Stille reaction, between aryl tin reagents and aryl halides, it was observed that by using LiCl as an additive that the cross-coupling efficiencies were significantly enhanced [44]. However, the positive effect of LiCl on our PEG-supported Stille variant seems to be only marginal (compare Table 4, entries 3 and 7). This result is more in line with previous reports which found that LiCl does not usually enhance the reaction between trialkyl tin reagents with aryl halides, but is generally more useful with aryl triflate electrophiles [52, 53]. The summary of these results is that the use of PdCl\({}_{2}\)(PPh\({}_{3}\))\({}_{2}\) in the presence of LiCl in DMF at a reaction concentration of 20 mM for 48 h, or 10 mM for 24 h, gives excellent yields for the monomethoxy-PEG\({}_{5000}\)-supported variant of the Stille cross-coupling reaction (97 and 98% respectively). This liquid-phase approach imparts a number of significant advantages over its solution-phase counterpart. The toxic tributyl tin derivatives are easily separated from the PEG-biaryl adduct **17a** by precipitation of the polymer-support into either _iso_-propyl alcohol or diethyl ether. Polymer recovery was \(>\)99% in each case.