Arylation without carboxylic

Carboxylic adds are obtained from aryl iodides by the reaction of chloroform under basic conditions without using CO[336],... 

In addition to providing fully alkyl/aryl-substituted polyphosphasenes, the versatility of the process in Figure 2 has allowed the preparation of various functionalized polymers and copolymers. Thus the monomer (10) can be derivatized via deprotonation—substitution, when a P-methyl (or P—CH2—) group is present, to provide new phosphoranimines some of which, in turn, serve as precursors to new polymers (64). In the same vein, polymers containing a P—CH group, for example, poly(methylphenylphosphazene), can also be derivatized by deprotonation—substitution reactions without chain scission. This has produced a number of functionalized polymers (64,71—73), including water-soluble carboxylate salts (11), as well as graft copolymers with styrene (74) and with dimethylsiloxane (12) (75). 

Sulfonic esters are most frequently prepared by treatment of the corresponding halides with alcohols in the presence of a base. The method is much used for the conversion of alcohols to tosylates, brosylates, and similar sulfonic esters. Both R and R may be alkyl or aryl. The base is often pyridine, which functions as a nucleophilic catalyst, as in the similar alcoholysis of carboxylic acyl halides (10-21). Primary alcohols react the most rapidly, and it is often possible to sulfonate selectively a primary OH group in a molecule that also contains secondary or tertiary OH groups. The reaction with sulfonamides has been much less frequently used and is limited to N,N-disubstituted sulfonamides that is, R" may not be hydrogen. However, within these limits it is a useful reaction. The nucleophile in this case is actually R 0 . However, R" may be hydrogen (as well as alkyl) if the nucleophile is a phenol, so that the product is RS020Ar. Acidic catalysts are used in this case. Sulfonic acids have been converted directly to sulfonates by treatment with triethyl or trimethyl orthoformate HC(OR)3, without catalyst or solvent and with a trialkyl phosphite P(OR)3. ... 

Diaryl sulfones can be formed by treatment of aromatic compounds with aryl sulfonyl chlorides and a Friedel-Crafts catalyst. This reaction is analogous to Friedel-Crafts acylation with carboxylic acid halides (11-14). In a better procedure, the aromatic compound is treated with an aryl sulfonic acid and P2O5 in polypho-sphoric acid. Still another method uses an arylsulfonic trifluoromethanesulfonic anhydride (ArS020S02CF3) (generated in situ from ArS02Br and CF3S03Ag) without a catalyst. ... 

Either or both of the R groups may be aryl. In general, dialkyl ketones and cyclic ketones react more rapidly than alkyl aryl ketones, and these more rapidly than diaryl ketones. The latter require sulfuric acid and do not react in concentrated HCl, which is strong enough for dialkyl ketones. Dialkyl and cyclic ketones react sufficiently faster than diaryl or aryl alkyl ketones or carboxylic acids or alcohols that these functions may be present in the same molecule without interference. Cyclic ketones give lactams. 

Several aryl esters of 6-chloromethyl-2-oxo-2//-l -benzopyran-3-carboxylic acid act as human Lon protease inhibitors (alternate substrate inhibitors)46 without having any effect on the 20S proteasome. Proteasomes are the major agents of protein turnover and the breakdown of oxidized proteins in the cytosol and nucleus of eukaryotic cells,47 whereas Lon protease seems to play a major role in the elimination of oxidatively modified proteins in the mitochondrial matrix. The coumarin derivatives are potentially useful tools for investigating the various biological roles of Lon protease without interfering with the proteasome inhibition. 

In a slightly less convenient procedure, but one which has general versatility, carbonylation of aryl (or vinyl) palladium compounds produces aryl, heteroaryl, and vinyl carboxylic acids. As with the other procedures, immediate upon its formation, the carboxylate anion migrates to the aqueous phase. Consequently, haloaromatic acids can be obtained from dihaloarenes, without further reaction of the second halogen atom, e.g. 1,4-dibromobenzene has been carbonylated (90% conversion) to yield 4-bromobenzoic acid with a selectivity for the monocarbonylation product of 95%. Additionally, the process is economically attractive, as the organic phase containing the catalyst can be cycled with virtually no loss of activity and ca. 4000 moles of acid can be produced for each mole of the palladium complex used [4],... 

The furoxan ring is notably resistant to electrophilic attack and reaction normally takes place at the substituents. Thus aryl groups attached to monocyclic furoxans and the homocyclic ring of benzofuroxans are nitrated and halogenated without disruption of the heterocycle. Reaction with acid is also slow protonation is predicted to occur at N-5 <89KGS1261> and benzofuroxans have pKj, values of ca. 8, similar to those of benzofurazans. Monosubstituted furoxans are, as expected, less stable and can be hydrolyzed to the corresponding carboxylic acid. Treatment of the parent furoxan (3) with concentrated sulfuric acid results in rearrangement to (hydroxyimino)acetonitrile oxide (HON=CHC=N —O ) and subsequent dimerization to bis(hydroxyiminomethyl)furoxan... 

Carboxylation of lithiated vinylic sulfoxides is also highly stereoselective, as shown by a one-pot experiment leading from optically pure (if)- -alkenyl aryl sulfoxides to optically pure methyl 2-arylsulfinyl-2-alkenoates without EjZ isomerization63. 

Proton acids can be used as catalysts when the reagent is a carboxylic acid. The mixed carboxylic sulfonic anhydrides RCOOSO2CF3 are extremely reactive acylating agents and can smoothly acylate benzene without a catalyst.265 With active substrates (e.g., aryl ethers, fused-ring systems, thiophenes), Friedel-Crafts acylation can be carried out with very small amounts of catalyst, often just a trace, or even sometimes with no catalyst at all. Ferric chloride, iodine, zinc chloride, and iron are the most common catalysts when the reactions is carried out in this manner.266... 

Scheme 5.20 Ni-catalyzed electrochemical carboxylation of aryl-acetylenes without stabilizing ligands [61].

Reactions between a representative range of alkyl- and aryl-amines and of aliphatic and aromatic acids showed that the direct formation of amides from primary amines and carboxylic acids without catalyst occurs under relatively low-temperature conditions (Scheme 1). The best result obtained was a 60% yield of N-bcnzyl-4-phenylbutan-amide from benzylamine and 4-phenylbutanoic acid. For all these reactions, an anhydride intermediate was proposed. Boric and boronic acid-based catalysts improved the reaction, especially for the less reactive aromatic acids, and initial results indicated that bifunctional catalysts showed even greater potential. Again, anhydride intermediates were proposed, in these cases mixed anhydrides of carboxylic acids and arylboronic acids, e.g. (I).1... 

Treatment of aryl-substituted alkenes with hypervalent iodine compounds can lead to the formation of phenyliodinated intermediates, which can be stabilized by the aryl substituent via the formation of phenonium ions. Subsequent nucleophilic attack might then lead to rearranged products. This behavior can be nicely seen by comparing the unsaturated carboxylic acids 78 in their reaction with (diacetoxyiodo)benzene 3. The substrate 78a without the phenyl substituent is cyclized to the phenyliodinated intermediate 79, which is then attacked by the acetate under the formation of lactone 81 [142]. Substrate 78b is, however, then stabilized by the formation of an intermediate phenonium ion 80 and attack by the acetate is accompanied by a 1,2-phenyl migration and 82 is generated, Scheme 35 [143]. 

Enolates prepared by deprotonation of carboxylic acid derivatives can also undergo elimination to yield ketenes. This is rarely seen with amides, but esters, thiolesters, imides, or N-acylsulfonamides can readily decompose to ketenes if left to warm to room temperature (Scheme 5.58). At -78 °C, however, even aryl esters can be converted into enolates stoichiometrically without ketene formation [462, 463],... 

ArN02 ArNH2.1 Aryl nitro compounds are reduced to arylamines by Ni2B at 40° in 3N HC1 or 15N NH4OH in 80-96% yield without effect on alkene, keto, nitrile, amide, carboxyl, or ester functional groups. Nitroso-, azoxy-, azo-, and hydrazobenzene are reduced to amines under the same conditions. 

The same group also showed that mono(cyclopentadienyl) mixed hydride/ aryloxide dimer complexes of several lanthanide elements (Y, Dy, Lu) could be synthesized easily by the acid-base reaction between the mixed hydride/alkyl complexes and an aryl alcohol [144]. These complexes reacted with C02 to generate mixed formate/carboxylate derivatives, which were moderately active initiators for the copolymerization of C02 and cyclohexene oxide, without requiring a co-catalyst. The lutetium derivative 21 was the most active (at 110°C, TOF = 9.4 h ), yet despite a good selectivity (99% carbonate linkages), the molecular weight distribution remained broad (6.15) (Table 6). 

Palladium-catalyzed carbonylation reactions with aryl halides are powerful methods of generating aromatic amides, hydrazides, esters and carboxylic acids [25]. We have previously reported the exploitation of Mo(CO)6 as a robust carbon monoxide-releasing reagent in palladium-catalyzed carbonylation reactions [26-29]. This stable and inexpensive solid delivers a fixed amount of carbon monoxide upon heating or by the addition of a competing molybdenum coordinating ligand (for example DBU). This allows for direct liberation of carbon monoxide in the reaction mixture without the need for external devices. 

The reaction sequence in the vinylation of aromatic halides and vinyl halides, i.e. the Heck reaction, is oxidative addition of the alkyl halide to a zerovalent palladium complex, then insertion of an alkene and completed by /3-hydride elimination and HX elimination. Initially though, C-H activation of a C-H alkene bond had also been taken into consideration. Although the Heck reaction reduces the formation of salt by-products by half compared with cross-coupling reactions, salts are still formed in stoichiometric amounts. Further reduction of salt production by a proper choice of aryl precursors has been reported (Chapter III.2.1) [1]. In these examples aromatic carboxylic anhydrides were used instead of halides and the co-produced acid can be recycled and one molecule of carbon monoxide is sacrificed. Catalytic activation of aromatic C-H bonds and subsequent insertion of alkenes leads to new C-C bond formation without production of halide salt byproducts, as shown in Scheme 1. When the hydroarylation reaction is performed with alkynes one obtains arylalkenes, the products of the Heck reaction, which now are synthesized without the co-production of salts. No reoxidation of the metal is required, because palladium(II) is regenerated. 

The synthesis of derivatives of quinoline from isatins and carboxylic acid anhydrides can also be realized without isolating the intermediate N-acyl derivatives. Thus, unsubstituted 2-quinolonecarboxylic acid containing the 14C isotope at position 3 was synthesized by the condensation of isatin 7 with the anhydride (H314CC0)20 [172], The unsubstituted acid 168 [163] and its 3-aryl derivatives 195 [173, 174] were obtained by heating the isatin 7 directly with the respective anhydrides. 

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