Sulfonylation Reagents

If diamines are treated with strong acylating or sulfonylating reagents, high yields of bis-derivatized products are usually obtained, even if a large excess of diamine is used [61] (Scheme 10.14). Because the derivatization reaction is very fast, it goes to... 

Alkanesulfonyl chlorides can also react by an initial elimination in water, mesyl chloride hydrolyses below pH 6.7 by an S 2 reaction of water at sulfur, between pH 6.7 an 11.8 by capture of the sulfene by water and above pH 11.8 by capture of the sulfene with hydroxide ion. An extended study of mesylations of phenols catalysed by various pyridines revealed a competition between the sulfene pathway and a general base-catalysed attack of the phenol, which was dependent on the pAa of both phenol and pyridine, with no mention of an A-mesylpyridinium ion. However, formation of an A-triflylpyr-idinium ion occurs immediately pyridine and triffic anhydride are mixed and this is probably the triflating species. Reaction via an A-sulfonyl quaternary ammonium ion therefore becomes important with more basic amines and more electrophilic sulfonylating reagents. 

Polymer-supported sulfonyl chlorides can be used for the selective monosulfonyl-ation of anilines, as demonstrated by the Ley group [71, 72], Commercially available polystyrene-DMAP (4-dimethylaminopyridine) was treated with different aryl sulfonyl chlorides to form polymer-bound sulfonylation reagents. These were reacted with substituted anilines to form an array of hydroxamic acids (Scheme 6.17), using a synthetic strategy involving polymer-bound reagents in all steps. The products were subsequently evaluated as histone deacetylase inhibitors. 

Alkenyl sulfones. The sulfonyl reagent condenses with aldehydes (catalyzed by piperidine at -20°C). 

In order to selectively modify the 6-hydroxy, the 2, 3-hydroxy, specially the 2-, can be shielded by binding with blocking groups. They reacts with the modification reagent to achieve the modified CDs. For example, first replace all the three hydroxyls of glucose unit using sulfonyl reagent, then remove the 6- substituent by 2- propanol potassium which is mixed in 2-propanol/benzene solution. Thereafter, the relevant modifiers can react with 6- only. Finally, remove the 2, 3- benzoyl via methanol/potassium hydroxide solution. 

Sulfonylation. Under Friedel-Crafts reaction conditions, sulfonyl haUdes and sulfonic acid anhydrides sulfonylate aromatics (139), a reaction that can be considered the analogue of the related acylation with acyl haUdes and anhydrides. The products are sulfones. Sulfonyl chlorides are the most frequently used reagents, although the bromides and fluorides also react ... 

On dehydration, nitro alcohols yield nitro-olefins. The ester of the nitro alcohol is treated with caustic or is refluxed with a reagent, eg, phthaUc anhydride or phosphoms pentoxide. A mil der method involves the use of methane sulfonyl chloride to transform the hydroxyl into a better leaving group. Yields up to 80% after a reaction time of 15 min at 0°C have been reported (5). In aqueous solution, nitro alcohols decompose at pH 7.0 with the formation of formaldehyde. One mole of formaldehyde is released per mole of monohydric nitro alcohol, and two moles of formaldehyde are released by the nitrodiols. However, 2-hydroxymethyl-2-nitro-l,3-propanediol gives only two moles of formaldehyde instead of the expected three moles. The rate of release of formaldehyde increases with the pH or the temperature or both. 

The PMBs, when treated with electrophilic reagents, show much higher reaction rates than the five lower molecular weight homologues (benzene, toluene, (9-, m- and -xylene), because the benzene nucleus is highly activated by the attached methyl groups (Table 2). The PMBs have reaction rates for electrophilic substitution ranging from 7.6 times faster (sulfonylation of durene) to ca 607,000 times faster (nuclear chlorination of durene) than benzene. With rare exception, the PMBs react faster than toluene and the three isomeric dimethylbenzenes (xylenes). 

Tnfluoroacetic anhydnde in a mixture with sulfuric acid is an efficient reagent for the sulfonylation of aromatic compounds [44] The reaction of benzene with this system in nitromethane at room temperature gives diphenyl sulfone in 61% yield Alkyl and alkoxy benzenes under similar conditions form the corresponding diaryl sulfones in almost quantitative yield, whereas yields of sulfones from deactivated arenes such as chlorobenzene are substantially lower [44] The same reagent (tnfluoroacetic anhydride-sulfunc acid) reacts with adamantane and its derivatives with formation of isomeric adamantanols, adamantanones, and cyclic sultones [45]... 

The chloride of triflic acid (trifluoromethanesulfonyl chloride) is an effective sulfonylating agent Like triflic anhydride, it usually reacts with alcohols and other nucleophiles with the formation of the corresponding derivatives of tnflic acid [69] However, in some reactions, it acts as a chlorinating reagent [98] The reactions of tnfluoromethanesulfonyl chloride with 1,3-dicarbonyl compounds or some carboxylic esters in the presence of a base result m the formation of chlonnated products in high yields (equation 49)... 

The Bts derivative is formed from the sulfonyl chloride, either using apro-tic conditions for simple amines or by the Schotten-Baumann protocol for amino acids (87-97% yield). The primary drawback of this reagent is that its stability depends on its quality. It can on occasion rapidly and exothermically lose SO2 to give 2-chlorobenzothiazole. ... 

Another chiral titanium reagent, 11, was developed by Corey et al. [17] (Scheme 1.24). The catalyst was prepared from chiral ris-N-sulfonyl-2-amino-l-indanol and titanium tetraisopropoxide with removal of 2-propanol, followed by treatment with one equivalent of SiCl4, to give the catalytically-active yellow solid. This catalyst is thought not to be a simple monomer, but rather an aggregated species, as suggested by NMR study. Catalyst 11 promotes the Diels-Alder reaction of a-bro-moacrolein with cyclopentadiene or isoprene. 

The most important group of derivatives for the amino function (Fig. 7-4) is the carbamate group, which can be formed by reactions with acids, acid chlorides or acid anhydrides. A series of chlorides as 2-chloroisovalerylchloride [1], chrysanthe-moylchloride [2] and especially chloride compounds of terpene derivatives (cam-phanic acid chloride [3], camphor-10-sulfonyl chloride [4]) are used. The a-methoxy-a-trifluoromethylphenylacetic acid or the corresponding acid chloride introduced by Mosher in the 1970s are very useful reagents for the derivatization of amines and alcohols [5]. 

With the chiral methyltitanium reagents 39, modified by the bidentate ligands A-sulfonyl-norephedrine 38, a pronounced enantioselectivity is observed in reactions with aromatic aldehydes. Considerably lower enantiosclcction is obtained with aliphatic aldehydes36. 

In contrast cyclic y-(rey/-butyldimethylsilyloxy)-a,/ -unsaturated sulfones undergo addition of organometallic reagents to give mainly trans-adducts after reductive removal of the sulfonyl group. 

---