Aryl benzenesulfonates

Many functional groups are stable under conditions for the alkylation of pseudoephedrine glycinamide enolates, including aryl benzenesulfonate esters (eq 18), rert-butyl carbamate and rerf-butyl carbonate groups (eq 19), tert-butyldimethylsilyl ethers, benzyl ethers, ferf-butyl ethers, methoxymethyl ethers, and alkyl chlorides. The stereochemistry of the alkylation reactions of pseudoephedrine glycinamide and pseudoephedrine sarcosinamide is the same as that observed in alkylations of simple A(-acyl derivatives of pseudoephedrine. 

The first example of the use of aryl benzenesulfonates as arylating species in a-arylation reactions of acyclic and cyclic ketones was reported by Buchwald and coworkers [49] in 2003. A catalytic system composed of a mixture of Pd(OAc)2 and 2-dicyclohexylphosphino-2, 4, 6 -triisopropylbiphenyl (XPhos), allowed the synthesis of the required a-arylated ketones in very good yields (Scheme 8.21) [49]. 

Scheme 8.21 Pd(OAc)2/XPhos-catalyzed a-arylation of ketones with aryl benzenesulfonates, as described...

Ligand 19 is water soluble, and has been employed in Suzuki coupling reactions conducted in aqueous media. Ligand 17 provides optimal results in Suzuki coupling reactions of aryl tosylates and aryl benzenesulfonates. Ligand 16 is thought to have the greatest substrate scope of the Buchwald biaryl-phosphine derivatives, and is widely used in... 

Except for the perfluoro cases, aryl sulfonates are generally less reactive than the halides. However certain catalyst systems can achieve reactions with benzenesulfonates and tosylates. The hindered biphenyphosphines are the most effective ligands. 

Mesylates are used for Ni-catalysed reactions. Arenediazodium salts 2 are very reactive pseudohalides undergoing facile oxidative addition to Pd(0). They are more easily available than aryl iodides or triflates. Also, acyl (aroyl) halides 4 and aroyl anhydrides 5 behave as pseudohalides after decarbonylation under certain conditions. Sulfonyl chlorides 6 react with evolution of SO2. Allylic halides are reactive, but their reactions via 7t-allyl complexes are treated in Chapter 4. Based on the reactions of those pseudohalides, several benzene derivatives such as aniline, phenol, benzoic acid and benzenesulfonic acid can be used for the reaction, in addition to phenyl halides. In Scheme 3.1, reactions of benzene as a parent ring compound are summarized. Needless to say, the reactions can be extended to various aromatic compounds including heteroaromatic compounds whenever their halides and pseudohalides are available. 

Heck olefination of a diazonium salt is a key step in the industrial synthesis of sodium 2-(3,3,3-trifluoropropyl)benzenesulfonate, en route to Novartis sulfonylurea herbicide Prosulfuron (Scheme 15) [46]. Pd(dba)2 (0.5-1.5 mol%, prepared in situ from PdCl2), is used as catalyst. After completion of the arylation step, charcoal is added, thus directly providing a heterogeneous catalyst for the subsequent hydrogenation step and enabling easy removal of the now supported catalyst by filtration. 

One of the challenges in the Suzuki-type cross-coupling is to extend this reaction from electron-rich aryl iodides, bromides, and triflates to less reactive aryl sulfonates and aryl chlorides, which show poor reactivity in terms of oxidative addition in the catalytic cycle. Aryl mesylates, benzenesulfonates, and tosylates are much less expensive than triflates, and are unreactive toward palladium catalysts. The Ni(0)-catalyzed Suzuki-type cross-coupling reaction of aryl sulfonates, including mesylates, with arylboronic acids in the presence of K3P04 has been reported [123]. 

Esters of aliphatic and aromatic sulfonic acids are conveniently prepared in high yields from alcohols and sulfonyl halides. A basic medium is required. By substituting sodium butoxide for sodium hydroxide in butanol, the yield of n-butyl p-toluenesulfonate is increased from 54% to 98%. Ethyl benzenesulfonate and nuclear-substituted derivatives carrying bromo, methoxyl, and nirro groups are prepared from the corresponding sulfonyl chlorides by treatment with sodium ethoxide in absolute ethanol the yields are 74-81%. Pyridine is by far the most popular basic medium for this reaction. Alcohols (C -Cjj) react at 0-10° in 80-90% yields, and various phenols can be converted to aryl sulfonates in this base. "... 

Buchwald investigated aminations of aryl tosylates in a detailed study [30]. Among a variety of ligands, X-Phos proved to be superior for a variety of coupling partners, while furthermore a catalyhc system generated from Pd(OAc)2, X-Phos and CS2CO3 in a toluene/t-BuOH solvent mixture allowed for the efficient coupling of benzenesulfonates. In addihon to commonly employed amine nucleophiles, amides could be arylated efihciently. 

However, one aromatic sulfonic acid is rather important. Sulfonic acid 83 has the common name para-toluenesulfonic acid (tosic acid), and it is commonly used as an acid catalyst because it is reasonably soluble on organic solvents. Tosic acid has been used several times in previous chapters, including Chapter 10 (Sections 10.3 and 10.6) and Chapter 11 (Section 11.4). Chapter 21 will describe the formal nomenclature of aryl sulfonic acids, but the lUPAC name of 81 is benzenesulfonic acid and 83 is 4-methylbenzenesulfonic acid. However, the common name is used most often for 83. 

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