Suzuki hindered arylboronic acids

Instead of aryl halides, arenediazonium salts are also excellent arylating agents in the Suzuki coupling, although more hindered arylboronic acids did not react The reaction is catalysed by several sources of ligand-free palladium such as Pd(OAc)2, Pd2(dba)3 and Pd/C at room temperature in dioxane without any added base [98]. Use of potassium aryl trifluoroborate salts also allowed the introduction of more sterically hindered aryl groups [99]. 

Furthermore, the Tedicyp/fPdClfCjHjljj system efficiently catalyzes the Suzuki coupling of sterically hindered substrates. Very high turnover numbers can be obtained for the coupling of sterically hindered aryl bromides with benzeneboronic acid or for the coupling of bromobenzene with sterically hindered arylboronic acids. Conversely, the formation of tri-ortho-substituted biaryl adducts requires a high catalyst loading (Equation 65) [87]. 

Recently, the groups of Fu and Buchwald have coupled aryl chlorides with arylboronic acids [34, 35]. The methodology may be amenable to large-scale synthesis because organic chlorides are less expensive and more readily available than other organic halides. Under conventional Suzuki conditions, chlorobenzene is virtually inert because of its reluctance to oxidatively add to Pd(0). However, in the presence of sterically hindered, electron-rich phosphine ligands [e.g., P(f-Bu)3 or tricyclohexylphosphine], enhanced reactivity is acquired presumably because the oxidative addition of an aryl chloride is more facile with a more electron-rich palladium complex. For... 

Watanabe, T. Miyaura, N. Suzuki, A. Synthesis of sterically hindered biaryls via the Pd-cat-alyzed cross-coupling reaction of arylboronic acids or their esters with haloarenes. Synlett 1992, 207-210. 

One of the key problems associated with the Suzuki cross-coupling was the lack of reactivity of aryl chlorides. This is unfortunate, because chlorinated aromatics are usually much cheaper and more readily available than other haloarenes. Equation 12.68 shows a solution to this problem where the addition of the base Cs2C03 and P(t-Bu)3, a sterically hindered and electron-rich phosphine, led to successful coupling of an aryl chloride and arylboronic acid.142... 

Suzuki and co-workers found that aryl triflates react with arylboronic acids [ArB(OH)2], in the presence of a palladium catalyst, to give biaryls in a reaction that is now known as Suzuki coupling.269 Even hindered boronic acids give good yields of the coupled product.2 0 Organoboranes, react with aryl triflates under these conditions as well. In a simple example, boronic acid 426 reacted with 3-bromopyridine in the presence of Pd(PPh3)4 to give a 90% yield of the biaryl 427.2 2... 

The enantioselective Suzuki-Miyaura reaction (SM) can be accomplished by using the chiral ligands 213 [37] or 631 [38], whose palladium complexes catalysed the crosscoupling reaction of sterically hindered iodides and bromides with also quite encumbered arylboronic acids furnishing the axially chiral, sterically demanded biaryls in moderate to good yields with low to moderate enantioselectivity. 

Suzuki coupling, and excellent results were obtained even with aryl chlorides and sterically encumbered arylboronic acids (Figure 9.8). The Nolan group also investigated the application of simple pre-formed [(NHC)Pd(OAc)2] complexes (NHC = IMes, IPr) in Suzuki coupling. Sterically hindered aryl and activated alkyl chlorides, bearing p-hydrogens, were successfully coupled (1 mol% [Pd], 70-100% yield, 0.5-7 h reaction times). 

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