Suzuki coupling reactions phenylboronic acid

Coupling Reactions of Areneboronic Acid Derivatives 149 Table3.2 Suzuki coupling of phenylboronic acid with a selection of atyl chlorides. 

Suzuki coupling reactions with aryl halides. Two as-prepared BaCei cPd c03. ( materials (x = 0.05 and 0.10) were successfully utihzed in several Suzuki coupling reactions. Both aryl iodides and aryl bromides react smoothly with 4-phenylboronic acid, eq 1, to yield the corresponding biatyls in high yields (> 95%). For both 4-bromoanisole and 4-iodoanisole, the biatyl yields reached nearly 100% in 3 min with BaCeo 95Pdoo503 5 as the catalyst, corresponding to an effective TON of ca. 2,000 and an effective TOF of nearly 50,000 h. Resnlts are smmnarized in Table 27.1. 

A parallel synthesis of a library of 2-aryl-6-chlorobenzothiazoles 112 involves a regioselective palladium-catalyzed Suzuki coupling reaction of 2,6-dichlorobenzothiazole 111 with arylboronic acids (1.1 equiv) under microwave irradiation <06TL3091>. When excess phenylboronic acid is used, Pd(PPh3)4 still provides 2-phenyl-6-chlorobenzothiazole exclusively, while 2-dicyclohexylphosphinobiphenyl 113 generates 2,6-diphenylbenzothiazole as the major product. 

Ruhland et al. used both the Suzuki and Heck (see above) reactions on solid support in their generation of libraries of biaryl- and styryl-substituted [3-lactams.45 A preliminary investigation was performed into the most generally suitable catalytic system for preparation of their libraries. This featured coupling of phenylboronic acid with a resin-bound iodophenyl [3-lactam 32 (Scheme 36) the latter compound had been formed from a... 

A similar Suzuki cross-coupling reaction has also been employed by Gill and Lubell in a synthesis of an unsaturated kainoid analogue.50 Vinyl triflates 97 and 98 were cross-coupled with phenylboronic acid using tetrakis(triphenylphosphine)palladium(0) to give the corresponding coupled products 99 and 100 with high efficiencies (Scheme 42). 

Treatment 1,5-oxazocine 480 with AcoO in presence of DMAP afforded in 55% yield the /V-acctyl-dibenzo-1,5-oxazocine 481 which underwent Suzuki coupling reaction with phenylboronic acid to give the phenyl substituted 1,5-dibenzoxazocine 482 (13%) (Scheme 96) <2005W0084296>. 

Suzuki coupling reaction of phenylboronic acids such as 74 with 4-bromopyridine [34]. Inada and Miyuara [35] have extended the method to 2-chloroquinoline 25. Therefore, the coupling between 25 and phenylboronic acid 74 led to 2-tolylquinoline 75 in 91% yield. The catalyst was recovered with ease and used in further coupling reactions. Not surprisingly, the couplings of phenylboronic acids with electron-rich chloroarenes were ineffective due to their slow oxidative addition to the palladium(O) complex. This reaction is an example where even quinolinyl chloride is a good substrate for the oxidative addition of Pd(0) if the chlorine atom is at the activated position (a or 8). 

The Suzuki cross-coupling reactions could also be extended to fused pyridazines bearing a halogen atom on the 1,2-diazine nucleus. For example, 7-bromo-3-(2-fluorophenyl)-6-[(1 -methyl-1/7-1,2,4-triazol-5-yl)methoxy] [ 1,2,4]triazolo[4,3-Z ]pyridazine (84) was successfully coupled with phenylboronic acid to yield 3-(2-fluorophenyl)-6-[(l-methyl-l//-l,2,4-triazol-5-yl)methoxy]-7-phenyl[l,2,4]triazolo[4,3-Z ]pyridazine (85) in 51% yield [35]. Compounds like 85 might give access to new anxiolytic drugs since trisubstituted... 

The Suzuki coupling reaction was examined between four different aryl halide substrates and phenylboronic acid on fresh catalyst. Initially, 4-bromo-benzotrifluoride was successfully coupled at 25 °C with 98 % conversion in 12 h. However, at 50 C the reaction was much faster with 99 % conversion in 1.8 h (curve 1 in Figure 2). Ethyl 4-bromobenzoate was also successfully coupled at 25... 

The catalyst could be reused in three consecutive runs for Suzuki coupling reactions between derivates of bromobenzenes and phenylboronic acid in m-xylene in the presence of different bases (e.g. K2CO3), producing biphenyls in almost unchanged yields of89-94%. The comparable yield using the supported PdQz catalyst was only 81%. 

Calo and coworkers reported the use of Pd nanoparticles in ionic liquids (quaternary ammonium salts) as catalysts for the Suzuki coupling reaction of aryl bromides and chlorides with phenylboronic acid. The catalytic system was found... 

The Pd complexes bound to the interior of apo-Fr catalyzed the Suzuki coupling reaction of 4-iodoaniline and phenylboronic acid to afford 4-phenylaniline (Scheme 10.5). 

The Suzuki-Miyaura cross-coupling reaction of the synthetically versatile aryl O-carbamate is applied in the construction of heterotriaryls 39 and 41 (Scheme 14.11). Heterobiaryl O-carbamates 38 and 40, both previously prepared by a DoM-Suzuki-Miyaura cross-coupling sequence, are involved in a Ni-catalyzed O-carbamate cross-coupling with phenylboronic acid to afford their corresponding heterotriaryls 39 and 41, respectively, in poor and excellent yields [64]. 

For the Suzuki coupling reactions, see (a) Miyaura, N., Yanagi, T, and Suzuki, A., The palladium-catalyzed cross-coupling reaction of phenylboronic acid with haloarenes in the presence of bases, Synth. Comm., //, 513 (1981) (b) Suzuki, A., Organoborates in new synthetic reactions, Acc. Chem. Res., 15, 178-184 (1982) (c) Huber, J., and Scherf, U., A soluble poly(para-phenylene) composed of cyclophane units poly(2,5-(oxydecanoxy)-l,4-phenylene] Macromol. Rapid Commun., 15, 897 (1994). 

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