Carbanions allylic sulfonyl

Allylic sulfonyl carbanions react with electrophiles such as alkyl halides and aldehydes at the a-position. Although relatively strong bases like Bu"Li and LDA are usually used for deprotonation of allylic sulfur compounds, including sulfones, a catalytic two-phase system that consists of a concentrated aqueous NaOH solution and a quaternary ammonium salt can be used to generate allylic sulfonyl carbanions. 1,1-Dilithiated allyl phenyl sulfone (equation 20) reacts with excess benzaldehyde to afford the 1,3-( )-diadduct, while l,ort/io-dilithiated allyl phenyl sulfone gives the l,ort/io-diadduct predominantly. Other examples of sulfur-substituted allylic anions are summarized in Table 1. 

Pathway A shows the most common reaction where the nucleophilic substitution reaction occurs at the electron-deficient carbon atom due to the strong electron-attracting character of the sulfonyl group. Nucleophilic displacements at the allylic position (SN2 reaction) are shown in pathway B. Pathway C is the formation of a-sulfonyl carbanion by nucleophilic attack on the carbon atom p to the sulfone moiety. There are relatively few reports on substitution reactions where nucleophiles attack the sulfone functionality and displace a carbanion as illustrated in pathway D3. 

Nucleophilic addition to a, -unsaturated sulfones has long been known. For example, treatment of divinyl sulfone with sodium hydroxide has been known to afford bis( -hydroxyethyl) sulfone "", while the reaction of a- and -naphthyl allyl sulfones and allyl benzyl sulfone " with alkali hydroxide or alkoxide gave -hydroxy or alkoxy derivatives. In the latter reaction, the allyl group underwent prototropy to the 1-propenyl group, which in a subsequent step underwent nucleophilic attack . Amines, alcohols and sulfides are known to add readily to a, -unsaturated sulfones, and these addition reactions have been studied widely. In this section, the addition of carbon nucleophiles to a, ji-unsaturated sulfones and the reactions of the resulting a-sulfonyl carbanions will be examined. 

Nucleophilic attack on a rt-allyl ligand of a metal complex occurs in general at one of the terminal carbons to afford allylated products. The attack, however, may be directed to the central carbon atom of the 7i-allyl group to produce cyclopropyl derivatives by appropriate choice of nucleophile, metal ligand and reaction conditions (equation 33). A variety of nucleophiles (pA"a > 20) including ester and ketone enolates and a-sulfonyl carbanions react with... 

In contrast, few examples of conjugate additions of nonallylic a-sulfinyl (or a-sulfonyl) carbanions have been reported (for allylic oc-sulfinyl carbanion additions, see Section 1.2.2.5.1). Notable is the dia-stereoselective addition of alkyl f-butyl sulfoxides (245) to a,(3-unsaturated esters (equation 20)187 which is complementary to the diastereoselective addition of enolates to 3-substituted-a,f3-unsaturated sulfoxides (equation 20). 

Acceleration of Claisen rearrangements.2 The Claisen rearrangement of an allyl vinyl ether is markedly accelerated by a stabilized a-sulfonyl carbanion at the 2-position. Thus 1 and 2 rearrange to the y,d-unsaturated ketone 3 in the presence of potassium hydride and 18-crown-6 at moderate temperatures. Rates can be further enhanced by addition of HMPT. Substitution of methyl groups on either the allyl or vinyl units does not affect the regioselectivity but can accelerate the rate of rearrangement. 

The preparation of 3,7-dimethyl-2-fra/ij-4-rranj-6-franj-octatrienoic acid (Scheme 62) is a good example of the introduction of a sulfonyl group from sodium sulfinate, of the coupling reaction of a sulfonyl carbanion and allylic bromide and finally of the elimination of the sulfonyl group in basic medium giving the aW-trans compound. The same method was used for vitamin A synthesis (Scheme 63). 

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),... 

Simple sulfonyl carbanions which do not contain additional carbanion-stabilising groups, e.g. carbonyl groups or heteroatoms, can be readily alkylated in high yield by modern techniques with the use of alkyllithiums and lithium amide bases. A number of allylic halides have been successfully used. In allylic halides, the halogen directly attached to the double-bonded carbon is relatively inert towards nucleophilic attack (Scheme 41). In this way, sulfones (96) can be transformed via desulfonation into vinyl halides (97) or into ketones (98) by hydrolysis (Scheme 41). In contrast to ordinary alkyl sulfones, triflones (99) can be alkylated under mildly basic conditions (potassium carbonate in boiling acetonitrile) (Scheme 42). The ease of carbanion formation from triflones (99) arises from the additional electron-withdrawing (-1) effect of the trifluoromethyl moiety. 

By far, the most widely used method is the alkylation of an a-sulfonyl carbanion followed by reductive removal of the sulfonyl group. Different electrophiles such as alkyl halides, sulfonates, sulfinates, acetates, oxiranes, and electron-deficient multiple bonds are employed for the formation of the new C-C bond. Palladium-catalyzed it-allylic alkylation with a-sulfonyl carbanions is also a commonly used method. After the C-C bond formation, the conditions for the final desulfonylation reaction with the appropriate reagent will depend on the structure of the sulfone intermediate. 

Synthesis of (+)-Chatancin. The alkylation of an a-sulfonyl carbanion derived from a y-alkoxy functionalized sulfone with an allylic bromide and subsequent reductive desulfonylation with Na/Hg constitutes a key step in the synthesis of the marine diterpene (+)-chatancin (Eq. 144).251... 

Synthesis of All-t/a/is-Geranylgeraniol. The type of alkylation described above for the synthesis of bacillariolide III is widely used in the synthesis of natural products due to the mild reaction conditions and high stereospecificity. The formation of the C-C bond takes place when activated a-sulfonyl car-banions derived from (3-ketosul tones, a-sulfonyl sulfones or, less often, allylic sulfones react with the H-allyl palladium complex. In the synthesis of all-trans-geranylgeraniol, the a-sulfonyl carbanion adds to the Ti-allylpalladium complex of 2-(prop-l-en-2-yl)oxirane. Final reductive desulfonylation affords the desired compound, as depicted in Eq. 147.254... 

The oxidative dimerization of the anion of methyl phenyl sulfone (from a Grignard reagent) in ethereal solution in the presence of cupric chloride in 5% yield has been reported47. Despite the reported48 poor stability of the a-sulfonyl C-centered radicals, Julia and coworkers49 provoked the dimerization (in 13 to 56% yields) of the lithiated carbanion of alkyl phenyl sulfones using cupric salts as oxidants. The best results are obtained with cupric triflates in THF-isobutyronitrile medium (56% yield for R = H). For allyl phenyl sulfones the coupling in the 3-3 mode is predominant. 

Nucleophilic Substitution of xi-Allyl Palladium Complexes. TT-Allyl palladium species are subject to a number of useful reactions that result in allylation of nucleophiles.114 The reaction can be applied to carbon-carbon bond formation using relatively stable carbanions, such as those derived from malonate esters and (3-sulfonyl esters.115 The TT-allyl complexes are usually generated in situ by reaction of an allylic acetate with a catalytic amount of fefrafcz s-(triphenylphosphine)palladium... 

In Entry 5, the carbanion-stabilizing ability of the sulfonyl group enables lithiation and is then reductively removed after alkylation. The reagent in Entry 6 is prepared by dilithiation of allyl hydrosulfide using n-bulyl lithium. After nucleophilic addition and S-alkylation, a masked aldehyde is present in the form of a vinyl thioether. Entry 7 uses the epoxidation of a vinyl silane to form a 7-hydroxy aldehyde masked as a cyclic acetal. Entries 8 and 9 use nucleophilic cuprate reagents to introduce alkyl groups containing aldehydes masked as acetals. 

Because of the ability of some leaving groups to stabilize an a-carbanion, the pH at which the substitution is performed can be critical. Electrophiles with such leaving groups (e.g. R-N02 [36, 37], R-S(=0)2R [38, 39], R-S(=O)R[40]) will usually undergo substitution only under neutral or acidic conditions, what limits the choice of suitable nucleophiles. Some nucleophilic displacements of nitro and sulfonyl groups, both under acidic and basic reaction conditions, are shown in Schemes 4.6 and 4.7. Allylic nitro groups can also be readily displaced by catalysis with palla-... 

Ab initio calculations and NMR spectroscopy have been used to probe the structure, aggregation, and reactions of sulfonyl-stabilized allylic norbomenyl and norbornyl carbanions. This has included characterization of the exo direction pyramidalized anionic carbon atoms. Lithiosulfones (10) and (11), which exist in THF at —108.5 °C as an approximately 1 1 mixture of monomeric and dimeric forms, have been found to equilibrate rapidly with the respective conjugate acids, (12) and (13), in both exo and endo forms at 100 °C. According to Li H - and H H -NOE experiments, the monomeric and dimeric species endo-(10) and endo- ll), having endo anions, seem to be preferred in THF solution. Ab initio calculations indicate that the C(2) atoms of endo-(10)(Li+) and endo-(ll)(Li+) are pyramidalized in the exo direction whereas the... 

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