Sulfones from aldehydes

Alkyl sulfonyl chlorides, having an a-hydrogen atom, react with enamines derived from aldehydes and cyclic ketones in the presence of triethylamine to give cyclic sulfones. Thus the enamine (22) gave the four-membered cyclic aminosulfone (143) on reaction with methanesulfonyl chloride (95). 

The condensation of sulfonyl chlorides with enamines (452,453) derived from aldehydes and ketones has led to four-membered-ring sulfones, presumably through such intermediates (454-464). Open sulfonation products have also been obtained, particularly from ketone-derived enamines and from a-disubstituted sulfonyl chlorides. 

The Modified Julia Olefination (or Julia-Kocienski Olefmation) enables the preparation of alkenes from benzothiazol-2-yl sulfones and aldehydes in a single step ... 

Mulzer (Scheme 8 upper left) obtained the a,/(-unsaturated ester 33 with Z configuration from aldehyde 26a via a Still-Gennari olefination with phosphonate ester 34. Reduction of the ester with DIBAH and application of L-imidazole-PPhj gives allylic iodide 35. This acts as electrophile on the -anion of sulfone 36. After reductive removal of the phenylsulfone, group 28b is obtained [23]. 

The addition of sulfur nucleophiles to aldehydes and ketones may be exemplified by the formation of hydrogensulfite (bisulfite) adducts (3.12). These are sulfonates that are water soluble. However, their stcric bulk means that whereas they are formed from aldehydes and methyl ketones, more highly substituted ketones are reluctant to form these derivatives. 

From a historical perspective, the a-(dialkylamino)nitrile anions were the first acyl anion equivalents to undergo systematic investigation. More recent studies indicate that anions of a-(dialkylamino)nitriles derived from aliphatic, aromatic or heteroaromatic aldehydes intercept an array of electrophiles including alkyl halides, alkyl sulfonates, epoxides, aldehydes, ketones, acyl chlorides, chloroformates, unsaturated ketones, unsaturated esters and unsaturated nitriles. Aminonitriles are readily prepared and their anions are formed with a variety of bases such as sodium methoxide, KOH in alcohol, NaH, LDA, PhLi, sodium amide, 70% NaOH and potassium amide. Regeneration of the carbonyl group can be achieved... 

The addition of metalated sulfones to aldehydes or ketones is a reversible reaction and the principal cause of failure in the Julia alkenation results from an unfavorable equilibrium at this stage. The reverse reaction is favored when the P-alkoxy sulfone adduct is sterically encumbered. Adducts derived from ketones are more vulnerable than those derived from aldehydes. Stabilization of the sulfone anion by conjugation with an aromatic ring or chelation with a proximate heteroatom are also important contributors to favoring the reverse reaction. However, by varying the metal counterion, the position of equilibrium can be adjusted. For example, the lithio derivative of the sulfone (61 Scheme 24) failed to... 

Enol phosphates of a-ketosulfones provide the key intermediate to alternate schemes leading to acetylenes. Acylation of phenyl sulfones with esters affords the ketone derivatives directly. Alternately, the ketones can be obtained by Moffat oxidation of the condensation products from aldehydes with sulfone anions. Conversion to the enol derivatives followed by treatment with Na/NH or Na(Hg) gives the acetylenes. 

Direct a-alkylation of anions of allylic sulfones 179 gives products 180 from which PhSOj can be eliminated with mild base (MeONa) to give fi-dienes 181. The more usual condensation of sulfones with aldehydes is not necessary and those adducts 169 may eliminate to give vinyl sulfones instead of alkenes.47... 

Initial progress was swift and the two subunits required for the CIO-C16 dithiane fragment, sulfone 12 and aldehyde 10, were easily prepared. Ester 13 was first converted to the mono-protected diol 18 by silylation followed by ester reduction (Scheme 4). The phenyl sulfone auxiliary was next installed in two steps by a Mitsunobu-like thioether formation with diphenyl disulfide and tributylphosphine followed by oxidation with Oxone . The resulting sulfone 19 was desilylated and the liberated hydroxyl group converted to an aldehyde with Swem s procedure. Subunit 12 was completed by formation of the dithiane from aldehyde 20 under standard conditions. 

The reaction between a carbanion derived from alkyl 3,5-bis(trifluoromethyl)phenyl sulfones and aldehydes affords, with good yields and stereoselectivities, the corresponding 1,2-disubstituted alkene through the Julia-Kocienski olefination reaction. This one-pot protocol can be performed using the phosphazene base at —78 °C and has been successfully used in a high yielding and stereoselective synthesis of various stilbenes such as resveratrol [47] (Scheme 5.28). 

Phenyl- 17/-tetrazol-5-yl sulfones were introduced as another alternative to phenylsulfones these lead to alkenes in a one-pot procedure from aldehydes. Usually the highest selectivities are obtained when using KHMDS.For instance, alkene 3 was obtained in 100% yield and an 84 16 E Z ratio with NaHMDS, whereas the use of KHMDS led to the same product in 59% yield and a 99 1 E Zratio (eq 56). 

The /3-hydroxy imidazolyl sulfone derivatives were readily prepared from imidazolyl sulfones and aldehydes in the presence of NaHMDS (eq 36). ... 

Much more widely used carbene precursors are tosylhydrazones, which are readily prepared from aldehydes or ketones by reaction with 4-toluenesulfonyl hydrazide. Tosylhydrazones produce transient diazo compounds by base-catalyzed elimination of toluenesulfinate. The diazo compound is not normally isolated, and decomposes to the carbene on heating. The whole process is known as the Bamford-Stevens reaction. The leaving group is not the famihar tosylate (toluene-p-sulfonate, p.CH3-C, H4S03 , TsO ), but the less famihar toluene-p-sulfinate (Ts , P.CH3-C5H4S02 ) (Scheme 5.7). 

A soln. of salicylaldehyde and methylenebis (ethyl sulfone) in toluene treated with 1.1 times the equimolar amount of piperidine, and refluxed in a flask fitted with a Dean-Stark trap until water separation ceases 2-ethylsulfonyl-benzofuran. Y 59.5%. F. e. and prepn. of l,2-ethylene-l,l-disulfones from aldehydes s. M. L. Oftedahl, J. W. Baker, and M. W. Dietrich, J. Org. Ghem. 30, 296 (1965). 

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