Sulfone reaction with aldehydes

In the condensation reaction between chloro- and bromo-methyl aryl sulfones and carbonyl compounds, a-sulfonyloxiranes were obtained. In this condensation reaction, bases such as potassium t-butoxides372, NaH373 and aqueous concentrated hydroxide with benzyltriethylammonium chloride under two-phase condensation were used374. In the reaction with aldehydes only the trans-epoxide isomers resulted, whereas lith-iofluoromethyl phenyl sulfone 289375 and 291376 were found to add to aldehydes affording /J-hydroxysulfones 290 and 292, respectively. 

Addition of sulfinate ions to the carbonyl group of aldehydes to form c-hydroxy sulfones (Bredereck et al., 1954, Bredereck and Bader, 1954) is also known, as is the participation of sulfinic acids as the acid component in Mannich-type condensation reactions with aldehydes (129) (Rawson and Engberts, 1970 Engberts and Strating, 1964, 1965). 

This topological rule readily explained the reaction product 211 (>90% stereoselectivity) of open-chain nitroolefins 209 with open-chain enamines 210. Seebach and Golinski have further pointed out that several condensation reactions can also be rationalized by using this approach (a) cyclopropane formation from olefin and carbene, (b) Wittig reaction with aldehydes yielding cis olefins, (c) trans-dialkyl oxirane from alkylidene triphenylarsane and aldehydes, (d) ketenes and cyclopentadiene 2+2-addition, le) (E)-silyl-nitronate and aldehydes, (f) syn and anti-Li and B-enolates of ketones, esters, amides and aldehydes, (g) Z-allylboranes and aldehydes, (h) E-alkyl-borane or E-allylchromium derivatives and aldehydes, (i) enamine from cyclohexanone and cinnamic aldehyde, (j) E-enamines and E-nitroolefins and finally, (k) enamines from cycloalkanones and styryl sulfone. 

Hydroxymethyl-substituted tetrahydrofurans have been prepared with high diastere-oselectivity by reaction of the carbanion derived from 3,4-epoxybutyl phenyl sulfone (g) with aldehydes in the presence of a mixture of lithium and potassium /-buloxidcs (Scheme 8).48 Initial formation of aldol-type adducts is a non-diastereoselective but reversible process thus, subsequent formation of one main diastereoisomer is controlled by the relative rates of cyclization. The configuration of the carbon stereocentre at the oxirane ring is inverted in the course of the 5 2 process, and two new centres are created diastereoselectively (up to 87 13 0 0). 

Coupling of the mannosyl pyridyl sulfone 37 with aldehydes 36a and 36b in the presence of Smij was remarkably efficient leading to only one diastereomer 38a and 38b in each case, as shown in Figure 23 That indeed no epimerization of the aldehyde had occurred under the reaction conditions was confirmed by comparing the coupling product with that obtained from the same C-glycosyl donor and the aldehyde earlier prepared by Jung and Choe (Fig. 17). ... 

Vinyl sulfones. The anion of 1 (n-BuLi) undergoes a Peterson reaction with aldehydes or ketones to afford vinyl sulfones directly in 50-85% yield. Use of dimethoxy-ethane as solvent is essential for satisfactory results. The reaction is not stereoselective. 

Table 19 Examples of the reaction of n- pentyl BTFP sulfone 250 with aldehydes (THF) ...

Paquette and coworkers [127], in a synthesis of the complex polyol antibiotic amfidinolu-3, made masterly use of the Julia-Kodenski olefination reaction. Two examples taken from that work are presented below. Reaction of sulfone 285 with aldehyde 284 (Scheme 92) carried out with KHMDS in THF (at - 78 °C to rt) gave the building block 286 with 90% yield but with relatively poor selectivity, EjZ 1>I. Free-radical isomerization of the mixture (benzene, AIBN, reflux) increased the isomer ratio, /2 6/1. 

Table 30 Reaction of halomethyl PT sulfones (PTSO2CH2X) with aldehydes induced by LHMDS (2 mol equivalents) in the presence of HMPA (2 mol equivalents)...

The reaction of y-(tributyltin)-/ ,y-imsaturated BT sulfone 332 with aldehydes has also been examined (Scheme 113). Selected results are presented in Table 33. 

Table 33 Reaction of f ,y-unsaturated sulfone 332 with aldehydes, according to...

It may rather be that in the case of third row substituents like R4P the relative acidity of cyclopropyl and isopropyl hydrogens is not as indicative of the carbanion configuration as in the case with the second row substituents C(0)R, CN and possibly NO2. As far as cyclopropyl sulfones are concerned one would therefore predict that the corresponding a-sulfonyl cyclopropyl anions may have a pyramidal configuration. The deprotonation of cyclopropyl phosphonates, followed by reaction with aldehydes, was recently published by Hirao and coworkers ... 

Alkyl phenyl sulfones (piCj,27) are nearly as acidic as esters hence they are readily deprotonated by n-BuLi, LDA in THF, or EtMgBr in THF to give a-metalated sulfones. Their reaction with aldehydes gives a mixture of diastereomeric P-phenylsul-fone alkoxide adducts. Reductive elimination of the benzenesulfinate moiety from the adduct to produce the alkene is usually slow. To minimize side reactions, the hydroxyl group is first converted to an acetate, benzoate, mesylate, or /7-toluenesul-fonate and then treated with an excess of sodium amalgam [Na(Hg), prepared by adding small pieces of sodium to mercury] in methanol to furnish the trans-dlk n P... 

Sulfoxides (1) may be oxidised to sulfones by treatment with hydrogen peroxide (in acetic acid) or peroxycarboxylic acids (see Chapter 10, p. 195). Sulfoxides can also be reduced to sulfides by powerful reducing agents, e.g. lithium aluminium hydride. The reduction can also be achieved by reaction with dichloroborane (13) in THF at 0°C without affecting other functional groups like C02R, COCI, CN or N02, and even side reactions with aldehyde and ketone groups are relatively slow (Scheme 8). 

Sulfonyl carbanions undergo aldol-type reactions with aldehydes and ketones to give p-hydroxy sulfones which can be converted into alkenes (the Julia reaction) (see Chapter 10, p. 197). With allyl methyl sulfones (75) and a,p-unsaturated carbonyl compounds (63),... 

Only the additions of aldehydes to these substrates that contain a phenyl group as the activating substituent have been reported so far. Phenyl vinyl sulfone reacts with aldehydes at ambient pressure and temperature, but reaction times of a couple of days to weeks are common, especially with less reactive aldehydes (Scheme 1.39). In view of the poor reactivity, the reaction conditions were further optimized. Among the various catalysts screened, DABCO proved to be the best DBU was too basic and led to polymerization. Heating (130 °C, sealed tube) could speed up the reaction but yields were lower by 10-20%. ... 

Reactions with Aldehydes. The sulfonyl-stabilized phosphorane reagent has been used for Wittig alkenation of aldehydes. For example, condensation with isonicotinaldehyde gave the a,p-unsaturated sulfone as a single fisomer in 76% yield (eq 3). It is noteworthy that analogous reaction with (methylsulfonylmethy-lene)triphenylphosphorane produced the corresponding methyl-sulfonyl alkene as a 1 1 mixture of the E/Zisomers. ... 

One of main routes to achieve new characteristics of polysulfones is polymer modification. There are two ways to functionalize PSFs. The first way is post-polymerization modification, in which the polymer is functionalized after polymerization. PSF can be chemically modified by both electrophilic and nucleophilic reactions to yield new polymers with specific properties. Electrophilic reactions (for example sulfonation, chloromethylation followed by aminolysis) take place in the electron-rich bisphenol A part of PSFs [4-9], whereas nucleophilic reactions (in example lithiation with Li-organic compounds followed by reaction with aldehydes, ketones or carboxylic acid esters) can be performed in the electron-deficient diarylsulfone [10-17]. 

Spirotryprostatin A 142 and B 143 are two powerfully bioactive indole alkaloids. Both compounds inhibit the cell cycle in the G2/M phase, and 143 shows cytotoxic activity on the growth of human leukemia cell lines. Meyers and Carreira reported a total synthesis of 143. The Kocienski modified Julia olefmation was used in the formation of trisubstituted olefin without scrambling at Ci8. The alkene 146 was prepared in 78% yield by reacting sulfone 145 with aldehyde 144. The final product 143 was obtained by four-step reaction from the intermediate 146. 

A similar strategy has been investigated by Barco et al. in their approach to the synthesis of piperidin-4-one derivatives 461 (Scheme 69). Starting from Merrifield-SH resin, Barco et al. prepared 4-benzylsulfonyl-l-triphenyl-phosphoranylidene-2-butanone 457 via addition of butanone/AcOH, oxidation of the sulfide to sulfone and selective bromination of the terminal methyl group. After reaction with aldehydes 458 to a. S-unsaturated ketones 459 a cyclization-elimination process occurs via addition of N-nucleophiles like benzylamine 460. 

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