Sulfinyl anions

A modification of the addition of (+ )-(/ )-4-methyl-l-(methylsulfinyl)benzenc to benzaldehyde was recently reported9. The sulfinyl anion is made with lithium diisopropylamide, transmeta-lated with zinc(II) chloride and then reacted with benzaldehyde. 

The first report on the carboxylation of an a-sulfinyl anion showed that the lithium salt of (S)-(methylsulfmylmethyl)benzene treated with carbon dioxide afforded (/ ,SS)-2-(mcthyl-sulfinyDphenylacetic acid, which was isolated in 30% yield after crystallization of the crude product64. 

Optically active substituted alkylidene cyclohexanes were prepared from sulfinyl esters (obtained by carboxylation of sulfinyl anions) by thermolytic elimination of the sulfinyl group65. 

More recently the stereoselectivity of the addition of sulfinyl anions to carbonyl groups was improved by introducing a sulfide group in the a-position30,31. The sulfoxide ( + )-(S)-(4-methylphcnylsulfinyl)(4-methylphenylthio)metliane was added to benzaldehyde to give the adduct 1 as a mixture of three diastereomers [(S5,15,27 )/(SS,17 ,2/J)/(S5,15,25) 55 30 15] which could be transformed into the corresponding a-methoxyaldehydc 4 in 67% yield with 70 % ee. The same reaction, when applied to phenylacetaldehyde, led to a product in 43 % yield with lower ee (46%). 

Formation of a-Sulfinyl Anions with Lithium Diisopropylamide and Subsequent Addition to a,/ -Unsaturatcd Ketones General Procedure1 ... 

To a solution of lithium diisopropylamide. prepared from 5.04 mL (35.6 mmol) of diisopropylamine, 22.3 mL (35.6 mmol) of a 1.6 M solution of butyllithium in hexane and 34 mL of THF at —78 C is added dropwise a solution of 5.44 g (32.4 mmol) of ( + )-l-[(R)-ethylsulfinyl]-4-methylbcnzene sulfoxide in 37 mL of THF. A suspension of lithium bromoacetate, prepared from 6.75 mL (48.6 mmol) of bromoacetic acid and 5.15 g (64.84 mmol) of lithium hydride in 50 mL of THF, is added at the same temperature to the yellow solution of the sulfinyl anion. The mixture is stirred for 5 min at — 78 °C, sat. aq NH4C1 is added, and then 10 M hydrochloric acid is added dropwise until the solution reaches pH 2. The mixture is extracted with ethyl acetate, the extracts are concentrated, chromatography of the residue gives the product yield 4.24 g (58%) mp 53-55rC (hexane/diethyl ether). 

In sulfoxides and sulfones an adjacent CH group is also deprotonated by strong bases. If one considers the sulfinyl (—SO—) or sulfonyl (—SOj—) groups to be functional groups, then these carbanions are d -synthons. It will be shown later (p. 48f. and 65f.), that these anions may either serve as nonfunctional, d -, d - or d -synthons. 

The reaction is believed to proceed via a six-membered cyclic transition state, analogously to the carbonyl addition of enolates, but the energy differences between boat- and chair-like arrangements are lower for x-sulfinyl carbanions69. Tor tert-butyl sulfoxides only anti- and, vn-products are obtained, arising from the approach onto the same diastereotopic face of the anion, but with different relative topicity. The exchange of lithium by zinc causes an increase of the anft-produci, but attempts to titanate the anion failed (see Table 3)69. 

The anions of 2-(arylsulfinylmethyl)oxazoles can be added to aldehydes to give 2-(l-aryl-sulfinyl-2-hydroxyalkyl)oxazoles which have been transformed into /1-hydroxy acids. With lithium bases, the enantioseleetivity could be increased to 50%. The use of a more chelating counter ion, such as magnesium, lowered the optical yields44. 

From studies on the addition of racemic allylic sulfoxide anions of 3-substituted l-(phenyl-sulfinyl)-2-propenes to racemic 4-tcrr-butoxy-2-cyclopentenone, it was found that (El-allylic sulfoxides give. vyw-products, and (Z)-allylic sulfoxides give anti-productsx. 

The anions of (/ )-a-sulfinyl ketimines undergo 1,4-addition to cyclic a./Tunsaturated esters and then cyclization to give predominately c/.v-fused annulation products243. These studies have been extended to include acyclic a,/l-unsaturated esters 24b,c. 

The addition of enolate anions to (E)- and (Z)-3,3,3-trifluoro-l-[(4-methylphenyl)sulfinyl]-1 -propene has been investigated (E)- and (Z)-a,/(-unsaturated sulfoxides undergo addition in the opposite stereochemical sense3,4. In general, yields and product diastereoselection are high. When the -position of the double bond of the enolate is substituted then all four diastereomer-ic products result. 

Active methylene compounds may be sulfinylated by reaction of their enolate anions with sulfinate ester7-1 This reaction has been investigated much in recent years and the compounds resulting from it have been of considerable use in asymmetric synthesis (see the chapter by Posner). Examples of the sulfinylation are given in the following paragraphs. 

Schneider and Simon82 prepared / -ketosulfoxides 47a and 47b by sulfinylation of the dianions of the methyl acetoacetates 48a and 48b with sulfinate ester 19 followed by decarboxylation of the intermediate products (Scheme 2). Apparently this avoids racemiz-ation experienced by others in the direct synthesis of these compounds9. /J-Ketosulfoxides are also available from the reaction of the anion derived from methyl p-tolyl sulfoxide with esters (see Section II.E). They can also be obtained, in some cases, through the hydrolysis of a-sulfinylhydrazones whose synthesis is described below. Mention has already been made of the synthesis of 2-p-tolylsulfinylcycloalkanones such as 32. 

Meyers and coworkers141 measured the pKa values of a number of arylthio-, arylsulfinyl-and arylsulfonyl-phenols. From their few results relating to the effects of 4 - R on 4-OH, Hogeveen138 inferred that relative influence of substituents was about the same in the three series, contrasting with what he had found in his various series of acrylic acids. He attributed this to the compensation of the polarizability effect (see above) by the influence of a(pd) conjugation in the anions of the sulfinyl and sulfonyl series. Meyers and coworkers141 were more interested in the effect of moving the OH from the 4- to the 2-position (see Section III.D). 

Papageorgiou and Benezra204 treated chiral r-butyl (-)-(S)- and ( + )-(R)-2-(p-tolylsulfinyl)propionate with an aldehyde, then pyrolyzed the mixture and obtained chiral a-(hydroxyalkyl)acrylate in 75% e.e. Similarly, condensation of the anion of ( + )-(R)-3-(p-tolylsulfinyl)propionic acid 159 with aldehydes was found to give the diastereomeric [i-sulfinyl-y-lactones, (+)-(Sc4,Rc5,Ps)-160a and ( + )-( c4,Sc5,l s)-160b in an approximate ratio of 60 40205. 

This review is concerned with the formation of cation radicals and anion radicals from sulfoxides and sulfones. First the clear-cut evidence for this formation is summarized (ESR spectroscopy, pulse radiolysis in particular) followed by a discussion of the mechanisms of reactions with chemical oxidants and reductants in which such intermediates are proposed. In this section, the reactions of a-sulfonyl and oc-sulfinyl carbanions in which the electron transfer process has been proposed are also dealt with. The last section describes photochemical reactions involving anion and cation radicals of sulfoxides and sulfones. The electrochemistry of this class of compounds is covered in the chapter written by Simonet1 and is not discussed here some electrochemical data will however be used during the discussion of mechanisms (some reduction potential values are given in Table 1). 

A highly stereoselective synthesis of the (3-substituted P-amino sulfone 271 involves the addition of a sulfonyl anion, derived from A-PMB sultam 268 upon treatment with NaHMDS, to chiral A-sulfinyl imine (5)-269 <06OL789>. Removal of the A-sulfinyl followed by basic workup affords amine 271. The stereochemical outcome of the adduct 270 was established via proton NMR analysis of the Mosher s amide derived from 271. 

Sulfinyl aziridines (162) were found to undergo a clean metallation by ethyl Grignard with loss of the sulfoxide moiety to give the aziridinyl anions 163, which in turn can be alkylated in the presence of copper(I) iodide to give new elaborated products (164) with the heterocyclic nucleus intact <00TL6495>. 

Recently, sulfinyl and sulfonyl peroxy radical intermediates 6a and 6b have been prepared by the reactions of aryl sulfinyl or sulfonyl chloride with superoxide anion radical, respectively. These peroxy intermediates show strong oxidizing abilities in various oxidations. This chapter will describe the properties and applications of a variety of sulfur and phosphorus peroxy compounds in oxidation reactions. For a more complete picture, readers should consult the original papers cited in the areas that most interest them. 

The anion crystallizes as a dimer with bonding occurring via a Li20, four-membered ring. Two further coordination sites on each Li4 arc occupied by the TMF.DA N-atoms. This result is fully consistent with the four-center chelate structure which was proposed before for a-lithio sulfoxides 39- 40 and believed to be responsible for the planar configuration of the anionic carbon atom, This chelation discriminates between the two diastereotopic faces and for this reason a-sulfinyl carbanions react with electrophiles in a highly stereoselective manner (see the following section). 

The quenching of [lithio(methylsulfinyl)methyl]benzene with iodomethane produced [l-(methyl-sulfinyl)ethyl]benzene in a 15 1 diastereomer ratio (with predominant inversion) independent of the origin of methyllithium used to generate the anion. However, the stereochemistry of the methylation of [lithio(methylsulfinyl)methyl]benzene is dependent on the nature of the methylating agent52 (Table 1). 

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