chapter 2 palladium catalysts in suzuki cross- coupling reaction
chapter 2 palladium catalysts in suzuki cross- coupling reaction
chapter 2 palladium catalysts in suzuki cross- coupling reaction
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Years later, Shen showed that aryl chlorides could be activated <strong>in</strong> Suzuki<br />
<strong>reaction</strong> <strong>in</strong> the presence of a bulky, electron-rich trialkylphosphane (PCy3, Cy:<br />
cyclohexyl) at 100 °C (Table 2.1, entry 1.) (Figure 2.9). It was speculated that the<br />
electron-richness of PCy3 might facilitate oxidative addition of the Ar-Cl bond to Pd(0)<br />
and that the steric demand of PCy3 might favor ligand dissociation to give an active<br />
monophosph<strong>in</strong>e Pd complex (Shen 1997). Later on, there are various types of ligands<br />
that were shown to be activat<strong>in</strong>g Pd for the <strong>reaction</strong>s of aryl chlorides. Some of which<br />
are illustrated <strong>in</strong> Figure 2.10.<br />
Cl<br />
EWG<br />
+ Ph-B(OH) 2<br />
PdCl 2(PCy 3) 2<br />
(EWG= 3-MeCO, 4-CHO, 3-CHO, 2-CHO, 3-NO 2, 3-(E)-CH=CH-COOMe)<br />
Ph<br />
EWG<br />
Figure 2.9. The example of Suzuki <strong>reaction</strong>s of aryl chlorides from literature<br />
(Source: Shen 1997)<br />
In 1998, Fu and co-workers described the use of the electron-rich<br />
trialkylphosph<strong>in</strong>e P(t-Bu)3 as a ligand <strong>in</strong> Suzuki coupl<strong>in</strong>g <strong>reaction</strong>s of deactivated and<br />
h<strong>in</strong>dered aryl chlorides with arylboronic acid. It was also found that P(t-Bu)3:Pd ratio<br />
between 1:1 or 1.5 :1 was the most effective (Littke and Fu 1998) (Table 2.1, entry 2).<br />
Prior to 1998, there were no reports on the <strong>palladium</strong> catalyzed Suzuki <strong>reaction</strong>s<br />
of electron-neutral or electron-rich aryl chlorides. In 1998, Buchwald and co-workers<br />
reported that am<strong>in</strong>ophosphane, 1 (Figure 2.10), is a very effective ligand for <strong>palladium</strong>-<br />
catalyzed Suzuki <strong>reaction</strong>s of electron-neutral and electron-rich aryl chlorides (Table<br />
2.1, entry 3) ( Old et al. 1998).<br />
Buchwald and co-workers subsequently determ<strong>in</strong>ed that biphenyl ligands, 2 and<br />
3 (Figure 2.10), can be even more effective than 1 <strong>in</strong> <strong>palladium</strong>-catalyzed Suzuki<br />
<strong>reaction</strong>s of aryl chlorides (Table 2.1, entry 4) (Wolfe and Buchwald 1999a, Wolfe and<br />
Buchwald 1999b, Wolfe et al. 1999).<br />
A variety of ligands conta<strong>in</strong><strong>in</strong>g P-O bonds have proven to be useful <strong>in</strong> Heck and<br />
Suzuki coupl<strong>in</strong>g <strong>reaction</strong>s (Zapf and Beller 2000). Pd(II)-phosphate complexes were<br />
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