Arylboronic sterically hindered

Poor yields are obtained in the coupling of rirt/iri-substituted arylboronic acids[506). Ba(OH) as a base gives good results for the coupling of these sterically hindered compounds[5l3], but unsatisfactory results are observed... 

Bidentate ligands with very wide bite angles (like dpephos or xantphos, Scheme 4) are likely to form unstable chelates prone to dechelation at elevated temperatures, thus giving another route to monophosphine species. The application of such ligands to the crosscoupling of sterically hindered bromides and arylboronic acids under strictly anhydrous conditions enforced by the addition of molecular sieves has been shown to be advantageous (118).398... 

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... 

This reaction can be carried out with secondary amines, sterically hindered primary amines, hydrazines or anilines in dichloromethane at room temperature. The range of potential nucleophilic partners includes alkenylboronic acids, and electroneutral as well as electron-rich (hetero-)arylboronic acids. The conversion of electron-poor boronic acids can be effected at elevated temperatures (MW) in suitable solvents. 

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. 

Reaction of Arylboronic Acids with Haloarenes Synthesis of Sterically Hindered Biaryls [110] (Scheme 2-66)... 

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... 

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]. 

The yields of the cross-coupling reaction with sterically hindered arylboronates were modest [72]. However, many ADs were best prepared by this method since it allows convergent syntheses. 

The SM reaction of sterically hindered arylboronic acids Preparation of 2-(2 -methoxy-46 -di-tert-butylphenyl)-3-methylpyridine (236) [IS)... 

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. 

Sterically hindered or// o-disubstituted arylboronic acids such as mesitylboronic acid (9) or arylboronic acids with electron-withdrawing substituents (10) do not provide satisfactory results due to the steric hindrance and competitive hydrolytic deboronation. Consequently, we reinvest ated the coupling reactions of sterically hindered arylboronic aids having two or//io-substituents or functional groups which accelerate hydrolytic deboronation. It was discovered that this difficulty can be overcome by using suitable bases and solvent systems examples are shown in eqs 8 and 9 (II). This procedure gives an excellent method for the synthesis of biaryls. 

Iodo-4-methoxybenzoic acid methyl ester has been cross coupled with sterically hindered arylboronic esters in a process that was optimized to obtain biaryls in good yields (e.g. Equation 49) [58]. 

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]. 

The SM reaction of sterically hindered arylboronic ester in the presence of sodium phenoxide as the base Preparation of 5-methoxycarbonyl-2-methoxy-2 ,4 6 -trimethylbiphenyl (359) [19]... 

---