Ary lation

The trtfluoromethyl group activates the fluorine in position 4 ofperfluorotolu ene toward reaction with carbon nucleophiles Examples on the use of perfluoro-toluene as an ary lation agent abound, and in all cases, the 4-fluonne atom is replaced predominantly or exclusively [86,87,88,89,90] (equation 48) Inperfluoromesity-lene, the aromatic fluorine atoms are activated toward SN Ar reaction, and a reaction with one equivalent of methylkthium causes smooth replacement of one fluorine atom [91] (equation 49)... 

A wide range of benzocyclic ketones have been accessed by intramolecular ary-lation using aldehyde groups.272 This intramolecular Friedel-Crafts-type acylation is promoted by iodinium species, using the reagent combination IPy2BF4-HBF4. 

With welwistatin precursor 28 in hand, the synthetic plan involved its ary-lation with indolyllead triacetate 17 in conditions similar to those established for the model system 18. However, this reaction failed to give the expected product 29 (Scheme 5), probably because of the steric hindrance imposed by the presence of the methyl and vinyl substituents, as shown by the fact that cyclohexanone derivative 24 gave the reaction in quantitative yield, affording compound 30 [20]. 

Coupling reactions involving PdCl2(dppf) are very selective. It has proven possible with catalyst to mono-alkylate or arylate dichlorobenzenes (equation 72) [although PdCl2(dppb), where dppb = bis(l, 2-diphenylphosphino)butane, also succeeds for the ary-lations] or dibromothiophenes104,106, and to alkylate or arylate the. E-isomer of isomeric mixtures of 1-bromo-lalkenes with excellent selectivity (equation 73)107. 

The use of (t-Bu)3P/Pd-catalysts in the arylation of indoles has been reported by both the Hartwig and Watanabe groups [50,118]. Moderate to good yields are observed in the coupling reactions, however, side products resulting from C-ary-lation at the 3-position are commonly isolated as well. Similarly, both groups reported the arylation of carbazoles as well. 

Allene carboxylic acids have been cyclized to butenolides with copper(II) chloride. Allene esters were converted to butenolides by treatment with acetic acid and LiBr. Cyclic carbonates can be prepared from allene alcohols using carbon dioxide and a palladium catalyst, and the reaction was accompanied by ary-lation when iodobenzene was added. Diene carboxylic acids have been cyclized using acetic acid and a palladium catalyst to form lactones that have an allylic acetate elsewhere in the molecule. With ketenes, carboxylic acids give anhydrides and acetic anhydride is prepared industrially in this manner [CH2=C=0 + MeC02H (MeC=0)20]. 

N-Ary piperazines can be synthesized using this catalyst and unprotected piperazines.IS Key to this protocol is the use of excess piperazine to favor mono-ary lation versus the di-arylated product. Moderate yields of the mono-arylated product can be obtained with a variety of aryl bromides. The major side product is the de-halogenated arene caused by the p-elimination pathway. 

Deallylation. Allyl carbonates and carbamates are readily cleaved " by treatment with Pd(OAc)2. There is a useful chemoselectivity for this reaction in that dimethylallyl esters and cinnamyl esters are not affected. An expedient route to isoflavanones and isoflavones from allyl chroman-4-one-3-carboxylate involves ary-lation with ArPbfOAcfa and treatment with Pd(OAc>2. The latter reaction removes the ester group to give isoflavanones when it is carried out in the presence of PhjP, HCOOH, and EtsN. Isoflavones are obtained when the keto esters are treated with Pd(OAc>2 and PhaPCHjCHaPPhj in refluxing MeCN. 

If the counterion (X) in the oxidative addition complex is iodide or bromide (and no thallium or silver salts are present) the dissociation of one of the phosphorus atoms in the bidentate ligand from the metal is probably attributed to the relatively high trans effect exerted by the halidesJ This reversible displacement facilitates formation of a neutral rr-complex, in which the rr-system of the electron-rich alkene is only weakly polarized. Therefore, after insertion and hydridopalladium halide elimination, a larger fraction of /3-arylated product is formed, since steric factors always favor terminal ary-lation. 

Some finer effects caused by additives were reported. Thus, the use of the pair rt-Bu4NOAc-KCl was used to control the selectivity of reductive elimination in the ary-lation of acrolein acetals (Scheme 2.7). Interestingly, a more usual reverse combination KOAc- -Bu4NC1 gave worse results with respect to selectivity [54, 55], which clearly shows that the Mizoroki-Heck reaction is often extremely sensitive towards subtle details of formulation of the catalytic system. As proposed by Cacchi and coworkers [54,68] for the -Bu4NOAc-KC1 cocktail [55-57], the coordination sphere of palladium is saturated to form an anionic complex 28 (28 29 + 30), in which palladium is not capable of coordinating to the aryl tt-system as in 31 (31 30, Scheme 2.7). 

Hierso, J.C., Fihri, A., Amardeil, R. et al. (2005) Use of a bulky phosphine of weak with palladium as a versatile and highly-active catalytic system allylation and ary lation coupling reactions at 10 -10 mol% catalyst loadings of ferrocenyl bis(difurylphosphine)/Pd. Tetrahedron, 61, 9759-66. 

Mauledn, P, Alonso, I. and Carretero, J.C. (2001) Unusual palladium-catalyzed cascade ary-lation of a,j8-unsaturated phenyl sulfones under Heck reaction conditions. Angew. Chem. Int. rf.,40, 1291-3. 

In a comparative study, Wilkinson s catalyst (84) was employed in intermolecular ary-lation reactions of methyl acrylate (1) and styrene (2). Rhodium catalyst 84 was reported to be more efficient than a cobalt precursor. Note, however, that the reproducibility of these results was recently questioned [58]. Simple aryl iodides were efficiently converted at 110°C (Scheme 10.30), but crr/zo-substituted aryl iodides required a higher reaction temperature of 150 °C. Aryl bromides and chlorides, as well as aliphatic halides, could not be converted using rhodium catalyst 84 [47]. 

Hypervalent aryl iodine reagents have also been used as the electrophile in direct ary-lation reactions. In these examples, the strongly oxidizing hypervalent iodine reagents are proposed to react with the intermediate Pd(II) species to generate a Pd(IV) intermediate. Subsequent reductive elimination of biaryl from this Pd(IV) intermediate is then believed to regenerate the active Pd(II) species (Equation 19.141). ... 

Recently, polystyrene-supported pyrrole-2-carbohydrazide (PSP) was combined with Cu(l) to make up a recyclable catalytic system (Cu(l)/PSP) for the N-(hetero)ary-lation of amines and imidazole (Huang et al., 2013). This heterogeneous catalyst could also be successfully applied to the assembly of imidazo[l,2-a]quinoxaline through the intramolecular cyclization of A -(2-iodophenyl)-l//-imidazole-2-carboxamide (Scheme 4.39). 

Knochel s group has been active in this field [170]. In 2012, the group published a report on the ary-lation of 2-methyl-5-membered heterocycles with 2,2,6,6-tetramethylpiperidyl (TMP) bases [170]. This had been, until then, an unsolved problem. In this report, 1,2-dimethylimidazole was converted to its zincated product and this was coupled with a variety of aryl bromides using Pd(dba)2 and SPhos (Scheme 1.51). 

Staying with Knochel s [171a] work, in 2011, the group reported remarkable diastereoselective ary-lations of substituted piperidines (Scheme 1.52 - only for substituted piperidin-2-ylzinc reagents). Both substituted piperidin-2-ylzinc and 4-ylzinc reagents (not shown in Scheme 1.52, but the conditions are otherwise identical) were formed. These authors also reported a 1,2-migration of Pd in the diastereoselective cross-coupling of A/-Boc-6-methylpiperidin-2-ylzinc chloride. 

In 2013, Satoh, Miura, and coworkers [39] reported the palladium-catalyzed decarboxylative ary-lation of readily available 3-benzoylacrylic acids with arylboronic acids in the presence of a copper salt oxidant, affording chalcone derivatives (Scheme 3.22). The decarboxylative arylation could also be achieved using aryl halides as an alternative aryl source (Scheme 3.22). 

To the best of our knowledge, there are very few reports on the use of other metal-based systems. However, in 2007, Sames and coworkers [42] reported the ruthenium-catalyzed decarboxylative ary-lation of cyclic 2-amino esters. This process provides a rapid avenue to a variety of 2-arylpyrrolidines and piperidines from commercially available proline, hydroxyproline, and pipecolinate esters (Scheme 3.25). Examination of the substrate scope also showed that many arylboronic acids and boronate esters serve as coupling partners. It was also demonstrated that the required amidine- or... 

Kalyani and coworkers have described the development of intra-molecular ary-lation of C(sp )—H bonds adjacent to an amide nitrogen, using aryl chlorides and bromides with a Ni(COD)-based catalyst system (Scheme S-dS)." ... 

While the reaction is somewhat insensitive to the electronic effect of the substituent on the aryl group, it is very sensitive to any steric effects. The reaction of 2-o-tolylpyridine is very slow and yields little product due to restricted conformation. Nitrogen-containing heterocycles other than pyridine also undergo this ary-lation reaction. Some examples are shown above. In this interesting case of iron... 

Product of 2-arylation is formed preferentially with little or no formation of 3-ary-lation product. Electron-withdrawing substituents seem the favor the reaction while the electron-donating groups may inhibit it Substituted pyrroles get phenylated at the 2-position with excellent regioselectivity yielding desired products in moderate to good yields. 

Potassium (2- or 4-nitrophenyl)acetates also undergo the decarboxylative ary-lation (Scheme 4.80) [83]. 

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