P-Sulfonyl esters

A total synthesis of (+ )-crinine (284) has been completed from the intermediate (+ )-l-oxocrinane (281) (Vol. XI, p. 368) by bromination to an a-bromoketone which was dehydrobrominated (LiCl in boiling DMF, 77% yield) to 282. The latter was reduced to 283 which, once transformed into the toluene-p-sulfonyl ester, gave by solvolysis the expected (+ )-crinine (284) as well as dehydration products (63). 

The decarboxylative RBR involves saponification-induced decarboxylation of a p-sulfonyl ester, leading to a-sulfonyl anion formation. W th in situ halogenation of the other a-center, the episulfone is formed, which produces the alkene fSchemp 8.11V This protocol works best when the doubly a-center is disubstituted, otherwise conpeting halogenation at that position results in a haloalkene product. ... 

The reaction of alcohols with acyl chlorides is analogous to their reaction with p-toluenesulfonyl chloride described earlier (Section 8.14 and Table 15.2). In those reactions, a p-toluenesulfonate ester was formed by displacement of chloride from the sulfonyl group by the oxygen of the alcohol. Carboxylic esters arise by displacement of chloride from a carbonyl group by the alcohol oxygen. 

Replacement of a benzene ring by its isostere, thiophene, is one of the more venerable practices in medicinal chemistry. Application of this stratagem to the NSAID piroxicam, gives tenoxicam, 136, a drug with substantially the same activity, nie synthesis of this compound starts by a multi-step conversion of hydroxy thiophene carboxylic ester 130, to the sulfonyl chloride 133. Reaction of that with N-methylglycinc ethyl ester, gives the sulfonamide 134. Base-catalyzed Claisen type condensation serves to cyclize that intermediate to the p-keto ester 135 (shown as the enol tautomer). The final product tenoxicam (136) is obtained by heating the ester with 2-aminopyridine [22]. 

Bis-acceptor-substituted diazomethanes are most conveniently prepared by diazo group transfer to CH acidic compounds either with sulfonyl azides under basic conditions [949,950] or with l-alkyl-2-azidopyridinium salts [951] under neutral or acidic conditions [952-954]. Diazo group transfer with both types of reagents usually proceeds in high yield with malonic acid derivatives, 3-keto esters and amides, 1,3-diketones, or p, y-unsaturated carbonyl compounds [955,956]. Cyano-, sulfonyl, or nitrodiazomethanes, which can be unstable or sensitive to bases, can often only be prepared with 2-azidopyridinium salts, which accomplish diazo group transfer under neutral or slightly acidic reaction conditions. Other problematic substrates include amides of the type Z-CHj-CONHR and P-imino esters or the tautomeric 3-amino-2-propenoic esters, which upon diazo group transfer cyclize to 1,2,3-triazoles [957-959]. 

Cleavage of the sulfonyl esters to the parent alcohols is accomplished in yields of 60-100% by treatment of the p-toluenesulfonates with 2-6 equivalents of sodium naphthalene in tetrahydrofuran at room temperature (yields 60-100%). Sodium naphthalene is prepared by stirring sodium with an equivalent amount or a slight excess of naphthalene in tetrahydrofuran for 1 hour at room temperature under an inert gas [701]. Benzenesulfonates and bromo-benzenesulfonates are also cleaved to the parent alcohols while alkyl methanesulfonates are reduced also to hydrocarbons [701]. 

Like sulfonyl esters, sulfonamides can be reduced either to sulfinic acids, or to thiols. Heating of p-toluenesulfonamide with fuming hydriodic acid and phosphonium iodide at 100° afforded 85% of p-thiocresol [703]. 

Very recently, the same group proposed an access to a-amino P-ketoesters from chiral P-enamino esters [12e]. The animation reaction was performed with sulfonyl-oxycarbamate 6e (1 to 3 equiv.) in dichloromethane without base over two days, using chiral p-enamino ester derived from C2 symmetric pyrrolidines 24 or (/ )-1-phenylethylamine 26 (Scheme 10). 

Attempted displacement of the 2-O-imidazole-l-sulfonyl ester of methyl 3,4,6-tri-C>-niethyl p-o-galactopyranoside with azide ion led to the formation of the corresponding 2,5-anhydro sugar [86], as illustrated in Scheme 17. The predominance of a ring-cpntraction... 

The Michael reaction of sulfonyl carbanions with a,p-unsaturated esters provides a useful preparation of cyclopropane esters, as shown in Scheme 47. In this sequence, the sulfonyl carbanion undergoes conjugate 1,4-addition to the a,p-unsaturated carbonyl compound followed by intramolecular elimination of the benzenesulfinate anion (Scheme 47). 

Use of Metals in Alcoholic Solvents. Magnesium in the presence of mercuric chloride as a catalyst is by far the most employed metal when the reductive desulfonylation is carried out in low molecular weight alcoholic solvents.112 Only a small number of examples exist where Na or Li in alcoholic solvents is used, mostly for the desulfonylation of alkyl sulfones. The use of Mg in a low molecular weight alcoholic solvent in the presence of mercuric chloride is an extremely convenient desulfonylation method for a wide variety of sulfones (Eq. 61).113 Although p-kctosul tones are inert towards this reagent,114 a-sulfonyl esters are efficiently desulfonylated by Mg in MeOH.115116... 

Preparation of p-toluenesulfonic esters 962 p-Toluenesulfonyl chloride (1.1 moles per mole of alcohol) is added to the alcohol (10 g) in dry pyridine (100 ml), cooled to —5° in an ice-salt bath. The mixture is shaken in an ice-bath until the sulfonyl chloride is dissolved, and then at 0° for a further 2 h. It is then treated with portions (1, 1, 1, 2, and 5 ml) of water at not more than 5°, each addition being spread over 5 min. Then a further 100 ml of water are added. If the toluenesulfonate crystallizes, it is filtered off if not, it is extracted with CHC13 or ether. The extracts are washed with ice-cold, dilute H2S04, water, and NaHC03 solution and dried over Na2S04. After removal of the solvent the crude ester is often treated directly with the salt MX. 

Solution Base catalyzed hydrolysis of a sulfonyl ester (R -SOaR) will yield an alcohol (ROH) and a sulfonic acid salt (R SOa"). Sec-butyl tosylate is a sulfonyl ester and will be hydrolyzed to sec-butanol and the anion of p-methyIbenzenesulfonic acid. The reaction is shown as ... 

The anions of malonate esters, cyclopentadiene, p-keto esters, ketones, aldehydes, a-nitroacetate esters, Meldrum s acid, diethylaminophosphonate Schiff bases, p-diketones, /3-sulfonyl ketones and esters, andpolyketides represent the wide variety of carbon nucleophiles effective in this reaction. Generation of the stabilized anions normally is... 

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