Elimination aryl halides

When allylic alcohols are used as an alkene component in the reaction with aryl halides, elimination of /3-hydrogen takes place from the oxygen-bearing carbon, and aldehydes or ketones are obtained, rather than y-arylated allylic alcohoIs[87,88]. The reaction of allyl alcohol with bromobenzene affords dihydrocinnamaldehyde. The reaction of methallyl alcohol (96) with aryl halides is a good synthetic method for dihydro-2-methylcinnamaldehyde (97). 

In the reaction of allylic ethers with aryl halides, elimination of /t-alkoxy group occurs in some cases. Intramolecular reaction of the glycal 127 afforded the cis-fused pyrano[2,3-c]pyran 129 via deoxypalladation as shown by 128 [74]. On the other hand, ring cleavage of 130 occurs by deoxypalladation to give 132 via 131 [75]. Furthermore, the fcjiy-annulated pyranoside 134 was obtained by domino HR without elimination of the allyl ether group in 133 [76]. 

In Grignard reactions, Mg(0) metal reacts with organic halides of. sp carbons (alkyl halides) more easily than halides of sp carbons (aryl and alkenyl halides). On the other hand. Pd(0) complexes react more easily with halides of carbons. In other words, alkenyl and aryl halides undergo facile oxidative additions to Pd(0) to form complexes 1 which have a Pd—C tr-bond as an initial step. Then mainly two transformations of these intermediate complexes are possible insertion and transmetallation. Unsaturated compounds such as alkenes. conjugated dienes, alkynes, and CO insert into the Pd—C bond. The final step of the reactions is reductive elimination or elimination of /J-hydro-gen. At the same time, the Pd(0) catalytic species is regenerated to start a new catalytic cycle. The transmetallation takes place with organometallic compounds of Li, Mg, Zn, B, Al, Sn, Si, Hg, etc., and the reaction terminates by reductive elimination. 

In the reaction of Q,/3-unsaturated ketones and esters, sometimes simple Michael-type addition (insertion and hydrogenolysis, or hydroarylation, and hydroalkenylation) of alkenes is observed[53,54]. For example, a simple addition product 56 to methyl vinyl ketone was obtained by the reaction of the heteroaromatic iodide 55[S5]. The corresponding bromide affords the usual insertion-elimination product. Saturated ketones are obtained cleanly by hydroarylation of o,/3l-unsaturated ketones with aryl halides in the presence of sodium formate, which hydrogenolyses the R—Pd—I intermediate to R— Pd—H[56]. Intramolecular hydroarylation is a useful reaction. The diiodide 57 reacts smoothly with sodium formate to give a model compound for the afla-toxin 58. (see Section 1.1.6)[57]. Use of triethylammonium formate and BU4NCI gives better results. 

An Q-arylalkanoate is prepared by the reaction of aryl halide or triflate with the ketene silyl acetal 74 as an alkene component. However, the reaction is explained by transmetallation of Ph - Pd—Br with 74 to generate the Pd eno-late 75, which gives the a-arylalkanoate by reductive elimination[76]. 

The unconjugated alkenyl oxirane 133 reacts with aryl halides to afford the arylated allylic alcohol 134. The reaction is explained by the migration of the Pd via the elimination and readdition of H—Pd—1[107]. 

The 2-substituted 3-acylindoles 579 are prepared by carbonylative cycliza-tion of the 2-alkynyltrifluoroacetanilides 576 with aryl halides or alkenyl tri-flates. The reaction can be understood by the aminopalladation of the alkyne with the acylpalladium intermediate as shown by 577 to generate 578, followed by reductive elimination to give 579[425]. 

Another method for the hydrogenoiysis of aryl bromides and iodides is to use MeONa[696], The removal of chlorine and bromine from benzene rings is possible with MeOH under basic conditions by use of dippp as a ligand[697]. The reduction is explained by the formation of the phenylpalladium methoxide 812, which undergoes elimination of /i-hydrogen to form benzene, and MeOH is oxidized to formaldehyde. Based on this mechanistic consideration, reaction of alcohols with aryl halides has another application. For example, cyclohex-anol (813) is oxidized smoothly to cyclohexanone with bromobenzene under basic conditions[698]. 

The reaction is of the 8 2 type and works best with primary and secondary alkyl halides Elimination is the only reaction observed with tertiary alkyl halides Aryl and vinyl halides do not react Dimethyl sulfoxide is the preferred solvent for this reaction but alcohols and water-alcohol mixtures have also been used... 

The generally accepted mechanism for nucleophilic aromatic substitution m nitro substituted aryl halides illustrated for the reaction of p fluoromtrobenzene with sodium methoxide is outlined m Figure 23 3 It is a two step addition-elimination mechanism, m which addition of the nucleophile to the aryl halide is followed by elimination of the halide leaving group Figure 23 4 shows the structure of the key intermediate The mech anism is consistent with the following experimental observations... 

Other aryl halides that give stabilized anions can undergo nucleophilic aromatic substitution by the addition-elimination mechanism Two exam pies are hexafluorobenzene and 2 chloropyridme... 

Unlike elimination and nucleophilic substitution reactions, fonnation of organo-lithium compounds does not require that the halogen be bonded to 5/) -hybiidized car bon. Compounds such as vinyl halides and aryl halides, in which the halogen is bonded to sp -hybiidized carbon, react in the sane way as alkyl halides, but at somewhat slower rates. 

The reaction between an alkoxide ion and an aryl halide can be used to prepare alkyl aryl ethers only when the ar yl halide is one that reacts rapidly by the addition-elimination mechanism of nucleophilic aromatic substitution (Section 23.6). 

Elimination-addition mechanism (Section 23.8) Two-stage mechanism for nucleophilic aromatic substitution. In the first stage, an aryl halide undergoes elimination to form an aryne intermediate. In the second stage, nucleophilic addition to the aryne yields the product of the reaction. 

In the arylations of enamines with very reactive aryl halides (352,370) such as 2,4-dinitrochlorobenzene, the closely related mechanistic pathway of addition of the enamine to the aromatic system, followed by elimination of halide ion, can be assumed. The use of n-nitroarylhalides furnishes compounds which can be converted to indolic products by reductive cycliza-tion. Less reactive aryl halides, such as p-nitrochlorobenzene, lead only to N-arylation or oxidation products of the enamines under more vigorous conditions. 

Aryl halides undergo substitution, although not through an Sn2 mechanism, but rather via a two-step addition-elimination mechanism. (An elimination-addition mechanism is also possible see Chapter 13, Problem 12.)... 

This reaction is not a bona fide Heck reaction per se for two reasons (a) the starting material underwent a Hg Pd transmetallation first rather than the oxidative addition of an aryl halide or triflate to palladium(O) (b) instead of undergoing a elimination step to give an enone, transformation 134 136... 

The mechanism of action of the cyanation reaction is considered to progress as follows an oxidative addition reaction occurs between the aryl halide and a palladium(O) species to form an arylpalladium halide complex which then undergoes a ligand exchange reaction with CuCN thus transforming to an arylpalladium cyanide. Reductive elimination of the arylpalladium cyanide then gives the aryl cyanide. 

It is a reaction of wide scope both the phosphite 1 and the alkyl halide 2 can be varied. Most often used are primary alkyl halides iodides react better than chlorides or bromides. With secondary alkyl halides side reactions such as elimination of HX can be observed. Aryl halides are unreactive. 

The synthetic applicability is rather limited, due to the various side-reactions observed, such as eliminations and rearrangement reactions. The attempted coupling of two different alkyl halides in order to obtain an unsymmetrical hydrocarbon, usually gives the desired product in only low yield. However the coupling reaction of an aryl halide with an alkyl halide upon treatment with a metal (the Wurtz-Fittig reaction) often proceeds with high yield. The coupling of two aryl halides usually does not occur under those conditions (see however below ) since the aryl halides are less reactive. 

Nucleophilic substitutions on an aromatic ring proceed by the mechanism shown in Figure 16.17. The nucleophile first adds to the electron-deficient aryl halide, forming a resonance-stabilized negatively charged intermediate called a Meisenlieimer complex. Halide ion is then eliminated in the second step. 

Alkylation reactions are subject to the same constraints that affect all Sn2 reactions (Section 11.3). Thus, the leaving group X in the alkylating agent R—X can be chloride, bromide, iodide, or tosylate. The alkyl group R should be primary or methyl, and preferably should be allylic or benzylic. Secondary halides react poorly, and tertiary halides don t react at all because a competing E2 elimination of HX occurs instead. Vinylic and aryl halides are also unreactive because backside approach is sterically prevented. 

The possible mechanism for the reactions involving stoichiometric amount of preformed Ni(0) complexes is shown in Fig. 9.8. The first step of the mechanism involves the oxidative addition of aryl halides to Ni(0) to form aryl Ni(II) halides. Disproportion of two aryl Ni(II) species leads to a diaryl Ni(II) species and a Ni(II) halide. This diaryl Ni(II) species undergoes rapid reductive elimination to form the biaryl product. The generated Ni(0) species can reenter the catalytic cycle. 

This cycle involves, first, a monoelectronic transfer from the nickel (0) complex to the aryl halide affording a Ni(I) complex and then an oxidative addition affording a 16 electron-nickel (II) which undergoes a nucleophilic substitution of Nu-, then a monoelectronic transfer occurs once again with a second aryl halide, and, last, a reductive elimination of the arylated nucleophile regenerates the active Ni(I) species. 

The palladium(O) complex undergoes first an oxydative addition of the aryl halide. Then a substitution reaction of the halide anion by the amine occurs at the metal. The resulting amino-complex would lose the imine with simultaneous formation of an hydropalladium. A reductive elimination from this 18-electrons complex would give the aromatic hydrocarbon and regenerate at the same time the initial catalyst. 

The method is quite useful for particularly active alkyl halides such as allylic, benzylic, and propargylic halides, and for a-halo ethers and esters, but is not very serviceable for ordinary primary and secondary halides. Tertiary halides do not give the reaction at all since, with respect to the halide, this is nucleophilic substitution and elimination predominates. The reaction can also be applied to activated aryl halides (such as 2,4-dinitrochlorobenzene see Chapter 13), to epoxides, " and to activated alkenes such as acrylonitrile. The latter is a Michael type reaction (p. 976) with respect to the alkene. 

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