Bromobenzene coupling reaction with

Bicyclic complexes containing an azetidine ring and a palladium atom 525 have been shown to be effective catalysts in Suzuki coupling reactions with bromobenzenes and with the generally less reactive chlorobenzenes. The catalyst was stable in air for several months without loss of activity and the catalyst loading in the reaction could be lowered to 0.1% without a decrease of yield in the reactions studied <2005JOM2306>. 

Beginning with a discussion of the utility of tin-substituted glycals, Dubois and Beau [198] utilized 2,3,6-tri-O-benzyl-l-tri-fx-butylstannyl-glucal in coupling reactions with various aromatic substrates. As shown in Scheme 7.74, tetrakis(triphenylphosphine)palladium catalyzed reaction with bromobenzene provided an 88% yield of the desired product. Additionally, when... 

Beginning with a discussion of the utility of tin substituted glycals, Dubois, et al.,12 utilized 2,3,6-tri-O-benzyl-l-tri-n-butylstannyl glucal in coupling reactions with various aromatic substrates. As shown in Scheme 4.2.1, tetrakis triphenylphosphinepalladium catalyzed the reaction with bromobenzene providing an 88% yield of the desired product. Additionally, when p-nitrobenzoyl chloride was used, dichloro dicyanopalladium effected the formation of the illustrated ketone in 71% yield. Unlike the reactions discussed in section 4.1, the products observed were Ci substituted glycals. Further elaborations of this chemistry demonstrated its compatibility with both unprotected hydroxyl groups as well as very bulky aromatic bromides.13 Additional reactions with dibromobenzene are addressed in Chapter 8. 

Arylation of C-H bonds is achieved by coupling reactions of C-H bonds with aromatic compounds such as halides, triflates, and organometallic reagents. Early works in this field involve the reaction of aryl halides with norbornene. As shown in Scheme 5, the coupling reaction of bromobenzene with norbornene in the presence of Pd(PPh3)4 as a... 

The arylation of heteroaromatic compounds is also achieved by aryl-aryl coupling reaction. The arylation of A-methylimidazole with bromobenzene occurs under palladium catalysis (Equation (62)).72 The arylation of thiazole with aryl iodide occurs at the 2-position under PdCl2(PPh3)2/CuI catalysis.73 In this case, tetrabutylammonium fluoride improves the activity of the catalyst. Alternatively, thiazoles and benzothiazole are efficiently arylated... 

As the last example of C-C bond-formation reactions catalyzed by alkaline earth hydroxides, we mention the recently reported a-arylation of diethyl malonate in the presence of a palladium catalyst and a base in a separate phase 299). The arylation of carbonyl compounds is a carbon-carbon coupling reaction between an aryl halide and an enolate, which is usually catalyzed by palladium salts in the presence of an appropriate base (300,301). The arylation of diethyl malonate with bromobenzene (Scheme 48) was performed with tetrachloropalladate as the... 

This diazotization reaction is compatible with the presence of a wide variety of substituents on the benzene ring. Arenediazonium salts are extremely important in synthetic chemistry, because the diazonio group (N=N) can be replaced by a nucleophile in a radical substitution reaction, e.g. preparation of phenol, chlorobenzene and bromobenzene. Under proper conditions, arenediazonium salts react with certain aromatic compounds to yield products of the general formula Ar-N=N-Ar, called azo compounds. In this coupling reaction, the nitrogen of the diazonium group is retained in the product. 

The optional site selective metallation of fluorotoluenes158 with the superbasic mixture of butyllithium and potassium fert-butoxide has been applied to the synthesis of the anti-inflammatory and analgesic drug Flurbiprofen.171 3-Fluorotoluene is selectively metallated in the 4-position with LIC-KOR in THF at — 75 °C to afford, after reaction with fluorodimethoxyborane and hydrolysis, the corresponding boronic acid in 78% yield. A palladium-catalyzed coupling with bromobenzene gives the 2-fluoro-4-methylbiphenyl in 84% yield. This four-step sequence can also be contracted to a one-pot procedure with an overall yield of 79%. A double metallation with the superbasic mixture lithium diisopropylamide/potassium tert-butoxide (LIDA-KOR)172 173 is then required to produce flurbiprofen. 

The organometallic-substituted 85 (M = a derivative of B, Zn, Sn) and halogeno-substituted siloles 85 (M = C1, Br, I) are suitable starting compounds for cross-coupling reactions. Pd-catalyzed coupling of 91 (R = Me, Ph) with 4-amino- and 4-heteroaryl-bromobenzenes affords the siloles 92 in high yield <20040M6205>. 

The efficacy of the BINAP/Pd-system to mediate C-N bond formation without stereochemical erosion has been taken advantage of by several groups. Diver and co-workers described the double amination or orfho-di-bromobenzene with (S)-a-methylbenzylamine to yield the desired C2-sym-metric diamine in 61% yield, >99% ee, and 91% de, Eq. (69) [85]. Schmalz reported a similar coupling reaction to prepare new ligands for asymmetric catalysis [45]. 

Homocoupling of halobenzenes. lodo- and bromobenzene couple to biphenyls in the presence of this activated Ni(0). Yields are definitely higher with the former substrate. ort/io-Substituents, particularly nitro groups, inhibit coupling. The main by-products result from reduction. This coupling reaction is generally superior to the Ullmann reaction. 

Figure 11 (middle spectrum) shows the IINS spectrum of a 5% Pd/C catalyst after use in the C-C coupling reaction of bromobenzene and styrene to give fra -stilbene. Even after solvent extraction to remove the complex organic reaction mixture, products, base, and salts, the IINS spectrum of the used catalyst shows the sharp bands typical of molecular species. These are superimposed on the C-H out-of-plane bending bands of the activated carbon catalyst support. Comparison with the spectra of trans- and c/.y-stilbene in Fig. 11 (top and bottom spectrum. 

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