Aryl bromides reactivity

Cradally, dais allows orgatiozitic reagents to be prepared from less reactive aryl bromides and secondary or tertiary alkyl bromides.. Alternatively, orgatiozitic iodides can be prepared by means of a paliadiurniOj-catalyzed reaction between alkyl iodides and Et2Zn iSdaeme 2.25) [53-56],... 

PdCl2(PPh3)2 and Cul in a mixture of Et2NH and DMF at 120 °C for 5-25 min were found to be suitable as a general protocol. For less reactive (hetero)aryl bromides and 2-chloropyridine, extra triphenylphosphine was added to improve the stability of the palladium catalyst (Scheme 49). 

Subsequently, an in situ Pd(OAc)j-imidazolium salt mixture, developed by Nolan and Grasa, has demonstrated its efficiency for the coupling of aryl bromides and even chlorides with aryl and vinylstannanes. This improved reactivity is due to the TBAF additive, whereby F anions coordinate to Sn forming hypervalent fluorostannate anions that are more reactive towards transmetallation to Pd [121] (Scheme 6.37). 

Surprisingly, diethyl 2-vinyl-[l,3]-dioxolane-4,5-diacetate 2 is very reactive (Entry 1). Whatever the aryl bromide, complete conversions are observed after 3h and high isolated yields (> 73%) toward the expected compound are achieved. No product issued from the alternative syn-/i-H-elimination is detected. In that case, we suggest that a specific interaction between the ester group and the palladium center could occur leading to a stabilized 7 membered-ring intermediate 7 avoiding thus the formation of undesired product. 

It has been found that a number of bidentate ligands greatly expand the scope of copper catalysis. Copper(I) iodide used in conjunction with a chelating diamine is a good catalyst for amidation of aryl bromides. Of several diamines that were examined, rra s-yV,yV -dimethylcyclohexane-l,2-diamine was among the best. These conditions are applicable to aryl bromides and iodides with either ERG or EWG substituents, as well as to relatively hindered halides. The nucleophiles that are reactive under these conditions include acyclic and cyclic amides.149... 

The order of reactivity of halides with magnesium is RI > RBr > RC1 (very few organomagnesium fluorides have been prepared), i) Aryl Grignard reagents are more easily prepared from aryl bromides and aryl iodides than from aryl chlorides, which react very sluggishly. 

Generally, monophosphine complexes can be generated by decomposition of suitable precursors, among which the most notable are palladacycles (Section 9.6.3.4.7). A spectacular example makes use of spontaneous disproportionation of a dimeric complex of Pd1 with very bulky ligands to give one of the most reactive catalytic systems known so far, which catalyzes the fast crosscoupling of arylboronic acids with aryl chlorides and hindered aryl bromides at room temperature (Equation (28)) 389... 

The series of wide-bite-angle, bulky ligands derived from a cyclobutene scaffold gave Pd complexes (117) showing appreciable activity in the cross-coupling of reactive aryl bromides with trimethylsilylacetylene. A considerable shift of electron density to the phosphorus atoms, probably arising from alternative aromatic canonical structures, may account for the ligand properties.422... 

Activated aryl chlorides, which are close in reactivity to unactivated aryl bromides, underwent reaction with the original P(o-tol)3-ligated catalyst.58 Nickel complexes, which catalyze classic C—C bond-forming cross-couplings of aryl chlorides, 9-64 also catalyzed aminations of aryl chlorides under mild conditions.65,66 However, the nickel-catalyzed chemistry generally occurred with lower turnover numbers and with a narrower substrate scope than the most efficient palladium-catalyzed reactions. 

A perhaps more exotic substrate for the Heck reaction is 1,2-cyclohexanedione [25], The reactivity of this molecule under Heck coupling conditions can probably be attributed to its resonance enol form. This reaction is attractive, because the literature contains relatively few examples of the preparation of 3-aryl-l,2-cyclohexane-diones. Yields varied from good to modest when classic heating and electron-rich aryl bromides were used, and reaction times typically ranged from 16 to 48 h. Similar yields were obtained under continuous microwave irradiation with a single-mode microwave reactor for 10 min at 40-50 W (Eq. 11.10) [25],... 

The Ni(II) complexes 6 and 7 have been found by Stiles [60] to be soluble catalysts for reductive dehalogenation when combined with NaBH4 or hydrazine at 25-45 °C in protic solvents. Reactivity toward the reducing system increased with the halogen content of the substrate. Aryl bromides were converted much faster than chlorides, polychlorobenzenes, however, reacted readily with stepwise loss of chlorine. 

Reactions of aryl halides with the reactive calcium required slightly higher temperatures, up to -30°C for aryl bromides and up to -20°C for aryl chlorides.1 2 3 4 5 Surprisingly, the active calcium reacted readily with fluorobenzene at room temperature to form the corresponding organocalcium reagent in near quantitative yield. 

It has been proposed that in this reaction CO2 reacts as an electrophile with [ArPd (PPh3)2] formed by reduction of the aryl-palladium(II) [102]. Aryl chlorides react too slowly with Pd° to enable an efficient carboxylation reaction. On the other hand aryl triflate and aryl bromide have similar reactivity. The synthesis of aryl carboxylic acids can then be obtained from phenols via the formation of the corresponding aryltriflate (Eq. 15) [29, 30] ... 

Despite the fact that aryl bromides are generally less reactive, o- and p-bromotoluenes could be efficiently vinylated with ethene in DMF/H2O with [Pd(OAc)2] + P(o-tolyl)3 as catalyst and Et3N as base [16]. With careful choice of reaction parameters (90 °C and 6 bar of ethene) all bromotoluene was converted to high purity ortho- or para-vinyltoluene. Under the conditions used, the reaction mixture forms two phases. In this case the main role of water is probably the dissolution of triethylamine hydrobromide which otherwise precipitates from a purely organic reaction medium and causes mechanical problems with stirring. 

The difference in the reactivity of benzylic versus aromatic halogens makes it possible to reduce the former ones preferentially. Lithium aluminum hydride replaced only the benzylic bromine by hydrogen in 2-bromomethyl-3-chloro-naphthalene (yield 75%) [540]. Sodium borohydride in diglyme reduces, as a rule, benzylic halides but not aromatic halides (except for some iodo derivatives) [505, 541]. Lithium aluminum hydride hydrogenolyzes benzyl halides and aryl bromides and iodides. Aryl chlorides and especially fluorides are quite resistant [540,542], However, in polyfluorinated aromatics, because of the very low electron density of the ring, even fluorine was replaced by hydrogen using lithium aluminum hydride [543]. 

Reduction of a mixture of two aryl halides is not generally a good route to the mixed biaryl. Either a statistical mixture of the three possible biaryls is formed or, if one aryl halide is more reactive, this forms a single biaryl after which, the second aryl halide reacts with itself. The principal exception to this generalisation involves the reduction of a 1 1 mixture of an aryl bromide and 1-chloropyridine. Oxidative-addition to Ni(o) is faster for the carbon-bromine bond. The second oxidative-addition to ArNi(i) is faster for the 2-chloropyridinc, possibly due to complexation from the pyridine nitrogen. Overall, the 1-aryipyridine is formed in 55-80 % yields [200]. 

Although aryl bromides and iodides reacted well without any additive (Scheme 32), tetrabutylammonium bromide (TBAB) was effective at improving the reactivity of aryl triflates under these conditions (Scheme 33). 

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