Ketone aryl bromides

DTBNpP and palladium(II) acetate provided an efficient catalytic system for the a-arylation of ketones. Aryl bromides were coupled with ketones using 0.25-0.5 mol% Pd(OAc)2/DTBNpP in toluene at 50 °C. Coupling of 2-bromophenol with ketones using the Pd/DTBNpP system provided an efficient route for the synthesis ofbenzo[f>]furans (14EJ07395). 

Nickel-bpy and nickel-pyridine catalytic systems have been applied to numerous electroreductive reactions,202 such as synthesis of ketones by heterocoupling of acyl and benzyl halides,210,213 addition of aryl bromides to activated alkenes,212,214 synthesis of conjugated dienes, unsaturated esters, ketones, and nitriles by homo- and cross-coupling involving alkenyl halides,215 reductive polymerization of aromatic and heteroaromatic dibromides,216-221 or cleavage of the C-0 bond in allyl ethers.222... 

Other approaches to tetrazoles were also recently published. Primary and secondary amines 195 were reacted with isothiocyanates to afford thioureas 196, which underwent mercury(II)-promoted attack of azide anion, to provide 5-aminotetrazoles 197 . A modified Ugi reaction of substituted methylisocyanoacetates 198, ketones, primary amines, and trimethylsilyldiazomethane afforded the one-pot solution phase preparation of fused tetrazole-ketopiperazines 200 via intermediate 199 <00TL8729>. Microwave-assisted preparation of aryl cyanides, prepared from aryl bromides 201, with sodium azide afforded aryl tetrazoles 202 . 

Normally acylation reactions would be considered standard chemistry but replacing an aryl bromide with a ketone under relatively mild conditions warrants attention. Here 23 is treated with 1,3-dimethylimidazolium iodide (1,3-dii) in refluxing THE leading to the formation of the ketone 24 (Equation 8) <1997H(45)2159>. 

Grignard reagents derived from aryl bromides are readily prepared and may be converted into organocadmium compounds by treatment with cadmium chloride (cf. Section 5.8.4, p. 616). Reaction of an organocadmium with a carboxylic acid chloride constitutes a convenient synthesis of aryl alkyl ketones. 

Arylation of silyl enol ethers.1 Silyl enol ethers of methyl n- or sec-alkyl ketones undergo arylation when treated with an aryl bromide and tri-n-butyltin fluoride and a... 

A procedure has been developed for the palladium-catalysed a-arylation of amides by aryl bromides using the zinc enolates of the amides. The reaction works well with bromoarenes carrying a variety of ring substituents and with bromopyridine. In addition, the reaction has been shown to be effective with morpholine amides to give products which are precursors for aldehydes and ketones.39 A new method has been reported for the allylation of aryl halides using homoallyl alcohols as the allyl source the palladium-catalysed reaction, which may be both stereo- and regio-sepecific, uses a retro-allylation reaction to form a a-allyl(aryl)palladium intermediate.40... 

The synthetic scheme often applied for the preparation of 3-aryl-3-(trifluoromethyl)-3//-diazirine nowadays is shown in Scheme 5a [60]. It starts by lithiation of an aryl bromide (38), which subsequently reacts with /V-ftrifluoroacetyl)piperidine 39 (easily prepared from trifluoroacetic anhydride and piperidine) under the formation of trifluoroacetophenone 40. Next, the ketone is converted into the corresponding oxime 41, after which the hydroxyl group is converted into its tosylate (42). Reaction with liquid ammonia (usually under pressure) allows the installment of the diaziridine group (43). Subsequent oxidation with iodine finally results in the diazirine (44). This five-step reaction sequence is especially compatible with acid-labile protective groups, which are often used to protect and/or install functionalities at the R position. 

Azoles can be produced from products of palladium-catalyzed hydrazone arylation and can serve as substrates for arylation reactions to produce N-aryl azoles. The Fischer indole synthesis uses N-ary I hydrazones, and these hydrazones can be generated by palladium-catalyzed chemistry. Benzophenone hydrazone was found by both the Yale and MIT groups to be a particularly effective substrate for palladium-catalyzed reactions, as summarized in Eq. (24) [140,141]. Reactions of benzophenone hydrazone with either aryl bromides or iodides occur in high yields using either DPPF- or BINAP-ligated palladium. These reactions are general and occur with electron-rich, electron-poor, hindered or unhindered aryl halides. The products of these reactions can be converted to hydrazones that bear enolizable hydrogens and are suitable for indole synthesis in the presence of acid and ketone [140]. 

Simultaneously with the report by Buchwald, Hartwig demonstrated that the DPPF/Pd-catalyst efficiently couples primary amines and electron-deficient and electronically neutral aryl bromides [29]. For example, the couplings of -bu-tylamine with aryl bromides possessing nitrile and ketone functional groups proceed with excellent yields, Eq. (66). 

Acetophenones and benzyl phenyl ketones are arylated not only on the a-posi-tion, but also on the two orfho-positions using excess aryl bromides (Eq. 63) [129]. The reaction proceeds via a-arylation (see Sect. 2.2) followed by aromatic arylation. The latter seems to occur via coordination of the enolate oxygen to arylpalladium species, as in the reaction of 2-phenylphenols and 1-naphthols (Eqs. 56-58). Benzanilides are similarly diarylated on the benzoyl moiety using aryl bromides or triflates (Eq. 64) [130]. AT-Arylation [ 131 ] is not observed under the given conditions. 

Olefins, acetylenes, nitro, and nitroso groups are saturated during this reaction but ketones are not affected. Aromatic chlorides are also cleaved 0 but this can be inhibited by running the hydrogenation in acid over a platinum catalyst. Even under these conditions, however, aryl bromides and iodides are lost, at least to some extent. 

Tt-Allylnickel halides. Billington has reviewed the preparation of these complexes from allylic halides using Ni(CO)4 or Ni(COD)2, and their use in synthesis, mainly of natural products (54 references). These complexes react with a wide range of both aliphatic and aryl bromides or iodides as well as aldehydes, ketones, epoxides, and quinones. One advantage is that both allyl ligands react. They do not react with acid chlorides, esters, ethers, nitriles, or acetals. 

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