Phenylboronic acid, reaction

Phenylboronic acid. The orientation of nitration in phenylboronic acid is very susceptible to changes in the medium (table 5.8). The high proportion of o-substitution in acetic anhydride is not attributable to a specific o-reaction, for the nt -ratios of the last tabulated pair of results are not constant. The marked change in the ratio was considered to be due to the formation in acetic anhydride of a complex, as illustrated below, which is 0 -orienting and activated as a result of the -t-1 effect. This species need only be formed in a small concentration to overwhelm... 

The parent system 4 has also been jnepared employing a double reductive ring closure of a dinitrodiphenylbenzene derivative (Scheme 25). The required starting material, 195, was prepared using a palladium-catalyzed coupling of 1,4-dibromo-2,5-dinittobenzene with phenylboronic acid and after reaction with tri-ethylphosphite in hot tert-butylbenzene, 4 could be isolated in a moderate yield (92JHC1237). 

To overcome these problems with the first generation Brmsted acid-assisted chiral Lewis acid 7, Yamamoto and coworkers developed in 1996 a second-generation catalyst 8 containing the 3,5-bis-(trifluoromethyl)phenylboronic acid moiety [10b,d] (Scheme 1.15, 1.16, Table 1.4, 1.5). The catalyst was prepared from a chiral triol containing a chiral binaphthol moiety and 3,5-bis-(trifluoromethyl)phenylboronic acid, with removal of water. This is a practical Diels-Alder catalyst, effective in catalyzing the reaction not only of a-substituted a,/ -unsaturated aldehydes, but also of a-unsubstituted a,/ -unsaturated aldehydes. In each reaction, the adducts were formed in high yields and with excellent enantioselectivity. It also promotes the reaction with less reactive dienophiles such as crotonaldehyde. Less reactive dienes such as isoprene and cyclohexadiene can, moreover, also be successfully employed in reactions with bromoacrolein, methacrolein, and acrolein dienophiles. The chiral ligand was readily recovered (>90%). 

Reaction of methyl a-L-rhamnopyranoside with triphenylboroxole gave a syrupy boronate ester which was characterized as a crystalline phenyl-carbamate. Removal of the phenylboronic acid residue gave a product identified as methyl a-L-rhamnopyranoside 4-N-phenylcarbamate, since it was identical with that resulting from removal of the ketal group from methyl 2,3-O-isopr opylidene-a-L-rhamnopyranoside 4-N-phenylcarbamate (12). This establishes the structure of the original ester as methyl a-L-rhamnopyranoside 2,3-phenylboronate (24). 

A careful assessment of the constitution of compound 10 led to the development of a rather efficient strategy featuring the Diels-Alder reaction (see Scheme 3). Although the unassisted intermole-cular reaction between 3-hydroxy-2-pyrone (16)23 and a,/ -unsatu-rated ester 17 is unacceptable in terms of both regioselectivity and chemical yield, compounds 16 and 17 combine smoothly in refluxing benzene and in the presence of phenylboronic acid to give fused bicyclic lactone 12 (61% yield) after workup with 2,2-... 

Although there are several reports in the literature on boron-mediated amide formations, the boron reagents had to be used in stoichiometric amounts.1-4-5-6-7-8-9 Recently, Yamamoto et al. presented the first truly catalytic method allowing for a direct amide formation from free carboxylic acids and amines as the reaction partners.10-1112 Best results were obtained by using phenylboronic acids bearing electron withdrawing substituents in the meta- and/or para-positions such as 3,4,5-trifluorophenylboronic acid or 3,5-bis(trifluoromethyl)boronic acid as the catalysts. 

The Suzuki reaction has been successfully used to introduce new C - C bonds into 2-pyridones [75,83,84]. The use of microwave irradiation in transition-metal-catalyzed transformations is reported to decrease reaction times [52]. Still, there is, to our knowledge, only one example where a microwave-assisted Suzuki reaction has been performed on a quinolin-2(lH)-one or any other 2-pyridone containing heterocycle. Glasnov et al. described a Suzuki reaction of 4-chloro-quinolin-2(lff)-one with phenylboronic acid in presence of a palladium-catalyst under microwave irradiation (Scheme 13) [53]. After screening different conditions to improve the conversion and isolated yield of the desired aryl substituted quinolin-2( lff)-one 47, they found that a combination of palladium acetate and triphenylphosphine as catalyst (0.5 mol %), a 3 1 mixture of 1,2-dimethoxyethane (DME) and water as solvent, triethyl-amine as base, and irradiation for 30 min at 150 °C gave the best result. Crucial for the reaction was the temperature and the amount of water in the... 

Remarkably, one year later Leadbeater described that biaryls can be synthesized via a Suzuki-type coupling under transition-metal free conditions [51, 52]. The reaction conditions were almost identical to those reported for the ligand-free process, with the difference being that a larger amoimt of Na2C03 and arylboronic acid were used. Only one successful example of a heteroaryl haUde substrate is shown namely, the coupling of 2-bromopyridine with phenylboronic acid (Scheme 32). 3-Bromothiophene did not couple under the same reaction conditions. Unfortimately, attempts to use heteroarylboronic acids such as 3-pyridinylboronic acid, 3-thienylboronic acid, and lH-indol-5-ylboronic acid on 4-bromoacetophenone completely failed. 

Ethyl 6-methyl-4-phenyl-2-(phenylthio)-l,4-dihydropyrimidine-5-carboxyla-te was easily synthesized from ethyl 6-methyl-4-phenyl-2-thioxo- 1,2,3,4-tetra-hydropyrimidine-5-carboxylate and phenylboronic acid via microwave-assisted Cu-mediated S-phenylation (Scheme 108) [107]. The reaction involves the use of a stoichiometric amount of Cu(OAc)2 and a two-fold excess of 1,10-phenanthroline as a hgand. 

Alternatively, 3-phenyl pyrazinone was prepared via Suzuki reaction, when a polymer-bound pyrazinone was irradiated with 4 equiv of phenylboronic acid, 5 equiv of Na2C03 and 20 mol % of Pd[P(Ph)3]4 as the catalyst in DMF as the solvent (Scheme 36). Contrary to the results obtained in solution phase [29], all attempts to drive the reaction toward the formation of disub-stituted compound, using higher equivalents of reagents or longer reaction times, were unsuccessful. Apphcation of aqueous conditions afforded mixtures of 3-mono and 3,5-disubstituted pyrazinones. 

The MH-type reaction of phenylboronic acids and conjugated olefins, such as butyl acrylate, acrylnitrile, and methyl vinyl ketone under Pd(0)-catalyzed... 

OS 44] [R 4a] [P 33] By switching on and off the electroosmotic-driven flow of one reactant, plugs can be inserted in the reaction channel [6]. 4-Bromobenzonitrile plugs (5 s) are inserted into a continuous phenylboronic acid stream. By this means, the effective concentration of the aryl halide in the micro channel can be increased. 

The facile arylation of aldehydes with arylboronic acid has prompted the exploration of asymmetric versions of this reaction. However, this field has been scarcely explored and only few examples have been reported in the literature, with moderate results. The first diastereoselective example was described by Ftirstner and coworkers. By reacting the Gamer aldehyde 15 with phenylboronic acid under their set of experimental conditions (i.e. RhClj-SH O, IPr HCl) (Scheme 7.4) [21], the secondary alcohol was obtained in higher selectivity than that observed in the addition of phenylmagnesium bromide reported by Joullie (de = 94% versus 66%), with the anti isomer as the major compound [29]. 

Xia and co-workers synthesised a number of Pd-NHC complexes (33, 34, 36) for carbonylative Suzuki reactions (Fig. 9.6) [41], Various aryl iodides were carbonylatively coupled (P = 1 atm) with either phenylboronic acid or sodium tetraphenylborate. All the complexes were highly active, but 33 provided the best results with >76% selectivity for ketone in all the reactions. Xia followed this work with the double carbonylation of various aryl iodides with several secondary amines using the catalysts [CuX(Mes)] (37-X) and [Cu(IPr)X] (38-X) (X = I, Br, Cl) (3 MPa, 100°C, 10 h) (Scheme 9.7) [42],... 

General procedure for Suzuki coupling. 4-Bromoanisole (125 pL, 1 mmol), phenylboronic acid (186 mg, 1.5 mmol), K2CO3 (0.55 g, 4 mmol) and the BaCei.j,Pdj,03.j, catalyst were mixed in a 20 ruL scintillation vial. A preheated 2-propanol/water solution (IPA/H2O, 1 1 v/v, 12 ruL, 80°C) was added, the vial was immediately placed on a hot plate stirrer and its temperature was maintained at (80 1) °C. The reaction mixture was stirred at 1000 rpm for 3 min, then cooled to room temperature. The 4-methoxybiphenyl product was extracted with diethyl ether (3 x 15 ruL). The organic fractions were washed with deionized water and dried with MgS04. After filtration, volatiles were removed under reduced pressure to yield the isolated product. 

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. 

Maitlis filtration test. To investigate whether the Pd-doped perovskite is the actual catalyst, or a reservoir of soluble Pd, a Maitlis filtration test (10) was performed. The reaction of 4-bromoanisole with 4-phenylboronic acid, catalyzed by BaCeo 95Pdo os02 95, was intemipted at 20 s and 1 min, corresponding to conversions of 16 and 45%, respectively, by filtering the hot reaction mixture to remove the solid perovskite. The filtrates were allowed to cool to room temperature without stirring. After 3 h, the biatyl yields in both samples were estimated to be 100% by H NMR. 

Catalyst recycling. The solid Pd-doped perovskite catalysts are easily filtered from the reaction mixtnre for reuse. The activity of the recycled BaCco 95Pdo.o502 95 catalyst was investigated in the coupling of 4-bromoanisole with 4-phenylboronic acid. The results in Table 27.3 show that high activity was retained even after seven cycles of catalyst use. 

Various phenols can be selectively hydroxymethylated at the ortho position by heating with paraformaldehyde and phenylboronic acid. An intermediate 18-1 having the formula C14H1302B for the case shown can be isolated prior to the oxidation. Suggest a structure for the intermediate and comment on its role in the reaction. 

Recently, Suzuki-type reactions in air and water have also been studied, first by Li and co-workers.117 They found that the Suzuki reaction proceeded smoothly in water under an atmosphere of air with either Pd(OAc)2 or Pd/C as catalyst (Eq. 6.36). Interestingly, the presence of phosphine ligands prevented the reaction. Subsequently, Suzuki-type reactions in air and water have been investigated under a variety of systems. These include the use of oxime-derived palladacycles118 and tuned catalysts (TunaCat).119 A preformed oxime-carbapalladacycle complex covalently anchored onto mercaptopropyl-modified silica is highly active (>99%) for the Suzuki reaction of p-chloroacetophenone and phenylboronic acid in water no leaching occurs and the same catalyst sample can be reused eight times without decreased activity.120... 

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