Regioselectivity Friedel-Crafts reactions

A solution to all these problems can be found by an alternative disconnection. Enone (1) could be made by an aliphatic Friedel-Crafts reaction from acid (7). Disconnection of the allyl group now gives synthon (8) and the regioselectivity problem disappears. 

The new family of phospholes with 2,4,6-trialkylphenyl substituent on the phosphorus atom show, in many respects, a special reactivity. Due to the flattening of the P-pyramid, the arylphospholes exhibit aromaticity and hence underwent Friedel-Crafts reactions. The regioselective functionalization through reaction with phosphorus tribromide gave a variety of phospholes with an exocyclic P-moiety. Novel phosphole platinum and rhodium complexes were prepared and a part of them was tested in hydroformylation reactions. 

Among the wide variety of organic reactions in which zeolites have been employed as catalysts, may be emphasized the transformations of aromatic hydrocarbons of importance in petrochemistry, and in the synthesis of intermediates for pharmaceutical or fragrance products.5 In particular, Friede 1-Crafts acylation and alkylation over zeolites have been widely used for the synthesis of fine chemicals.6 Insights into the mechanism of aromatic acylation over zeolites have been disclosed.7 The production of ethylbenzene from benzene and ethylene, catalyzed by HZSM-5 zeolite and developed by the Mobil-Badger Company, was the first commercialized industrial process for aromatic alkylation over zeolites.8 Other typical examples of zeolite-mediated Friedel-Crafts reactions are the regioselective formation of p-xylene by alkylation of toluene with methanol over HZSM-5,9 or the regioselective p-acylation of toluene with acetic anhydride over HBEA zeolites.10 In both transformations, the p-isomers are obtained in nearly quantitative yield. 

As mentioned before, alkyl radicals and acyl radicals have a nucleophilic character therefore, radical alkylation and acylation of aromatics shows the opposite reactivity and selectivity to polar alkylation and acylation with the Friedel-Crafts reaction. Thus, alkyl radicals and acyl radicals do not react with anisole, but may react with pyridine. Eq. 5.1 shows the reaction of an alkyl radical with y-picoline (1). The nucleophilic alkyl radical reacts at the 2-position of y-picoline (1), where electron density is lower than that of the 3-position. So, 2-alkyl-4-methylpyridine (2) is obtained with complete regioselectivity. When pyridine is used instead of y-picoline, a mixture of 2-alkylpyridine and 4-alkylpyridine is obtained. Generally, radical alkylation or radical acylation onto aromatics is not a radical chain reaction, since it is just a substitution reaction of a hydrogen atom of aromatics by an alkyl radical or an acyl radical through the addition-elimination reaction. Therefore, the intermediate adduct radical (a complex) must be rearomatized to form a product and a hydrogen atom (or H+ and e ). Thus, this type of reactions proceeds effectively under oxidative conditions [1-6]. 

There are few studies on the metal triflate-catalyzed addition of pyrroles to a, 1-unsaturated compounds <2001 AGE 160, 2001TL8063>. The Friedel-Crafts reaction of homochiral pyrrole derivatives 450 with a,P-unsatu-rated esters catalyzed by metal triflates furnished conjugated addition products 451 in good yields without racemiza-tion (Equation 107) <2004S2574>. The addition worked regioselectively at C-5 of pyrrole. The best yields were obtained by using yttrium triflate and methyl 4-phenyl-2-oxobut-3-enoate. The diastereoisomers were separated by column chromatography. 

Two types of 3-benzoylbenzo[7]furans were regioselectively prepared from their corresponding starting materials 2-methylbenzo[ ]furan and 2-benzylbenzo[7]furan through a Friedel-Crafts reaction pathway, as shown in Scheme 47 <2002JME623>. 

It is well known that Friedel-Crafts acylation of aromatic compounds requires more than one equivalent of a Lewis acid relative to the substrate to bring the reaction to the completion, because the ketone produced deactivates the Lewis acid by complexation. Despite this, only 1 mol % TiCl(OTf)3 and 10 mol % TfOH in di-chloromethane or acetonitrile proved sufficient for the acylation shown in Eq. (175) this is, therefore, a catalytic Friedel-Crafts reaction [434]. The high regioselectivity obtained is also useful. 

This is clearly some sort of Friedel-Crafts reaction with an alkyl halide and AICI3 as the reag The alkyl halide forms a cation very easily because of the MeO group. Now we can draw mechanism and we won t worry about the regioselectivity until we have. 

The Friedel-Crafts reaction shows useful regioselectivity using the AICI3-DMF system, such that certain substituted benzophenones and benzodioxins are readily prepared. 

The Heck reaction makes a C-C bond and adds a highly functionalised fragment that can be elaborated into many other functional groups. The same is true of the Friedel-Crafts reaction that generally works well with azoles or other heterocycles able to do electrophilic substitution. As usual, it is best to have only one free position so that no regioselectivity problems arise. In the Heck reaction, the site of attack is marked by the iodine atom, but the Friedel-Crafts can occur at any free position. Our example is a pyrazole that acylates cleanly with Lewis acid catalysts to give eventually the herbicide pyrazolate 196. 

Friedel-Crafts reactions. Phenylsulfenylation is conveniently carried out using N--oenylthiophthalimide. Acylation of benzodioxin derivatives in the presence of AlCl,-A.M.A without solvent is regioselective. This complex behaves similarly to AICI3-DMSO a.-d AIC1,-DMF. 

Benzoylation. The regioselective Friedel-Crafts reaction of activated arenes with a,a,a-trichlorotoluene in refluxing 1,2-dichloroethane (53-97% yield) is catalyzed by HZSM-5 zeolite. 

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