Sulfone-Stabilized Carbanions

Cory and Renneboog53 have devised an efficient bicycloannulation for the synthesis of tricyclo[3.2.1.02,7]octane-6-one (66) as shown in equation 63. The method involves three steps (1) the enolate undergoes an initial conjugate addition to phenyl vinyl sulfone, (2) the resulting sulfone-stabilized carbanion undergoes an intramolecular Michael addition to the enone, and (3) the resulting enolate displaces phenylsulfinyl moiety from the tricyclooctanone. The amount of HMPA (3 mol equivalents) is critical for effective cyclization of the enolate. 

Clearly, the oxygen atoms are important—the best anion-stabilizer is the sulfone, followed by the sulfoxide and then the sulfide. You could compare deprotonation of a sulfone with deprotonation of a ketone to give an enolate Chapter 21). Enolates have a planar carbon atom and the anion is mainly on the oxygen atom. Sulfone-stabilized carbanions have two oxygen atoms and the anionic centre is probably planar, with the negative charge in a p orbital midway between them. Carbanions next to sulfones are planar, while anions next to sulfoxides and sulfides are believed to be pyramidal (sp3 hybridized). 

Sulfone stabilized carbanions attached at C-2 substantially accelerate the Claisen rearrangement (Scheme 22) these species may be generated from either regioisomeric precursors [142]. These processes take place with high levels of internal asymmetric induction [ 143], and the scope of the process is broad and it has been extensively studied. This acceleration was also noted for the related sulfinyl carbanions, albeit with low yields and in the case of sulfilimines no internal asymmetric induction was observed [144]. 

This cyclization reaction is not restricted to sulfone-stabilized carbanions. Indeed, phosphorus ylides, ester- and ketone-enolates participate also in the 5-endo-dig carbometallation reaction [17a]. The synthesis of fused bicyclo as well as spirobicyclo derivatives can be accomplished via the intramolecular carbometallation reactions of various stabilized carbanions with alkoxyacetylenes [17a]. Moreover, some asymmetric... 

The few examples indicate that sulfone-stabilized carbanions should react normally with electrophilic animating reagents (Eqs. 145158 and 146465) with the caveat that free a-amino sulfones are unstable.158,465 The (3,y-unsaturated sulfone 74 is animated at the y-position (Eq. 147),250 presumably by an ene reaction. The preparation of a-tosyl azides from nitronates was shown above in Eq. 144. The scope of this reaction does not seem to have been determined. Reaction of the anions of nitrobenzyl aryl sulfones with l-oxa-2-azaspiro[2.5]octane (13a) gives nitrobenzaldehydes by cleavage of the initially formed amination products.466 Similarly, reaction of the lithium salt of benzyl phenyl sulfone with phenyl azide gives benzilydeneaniline and phenyl sulfinate.467 No reports on animations of sulfoxide-stabilized carbanions were found. 

Sulfur-containing groups at an a-position stabilize carbanions. All these species, i.e., the a-sulfonyl 6281-102, a-sulfmyl 6346-80, a-sulfenyl 645,103,104 and a-sulfonio carbanions 65105-1 ancj those derived from sulfonates 66 and sulfonamides 6795 may retain their... 

The utility of the creation of a y-lactone enolate through 1,4-addition of a carbanion and its interception by an electrophile has also been demonstrated in other classes of natural products, e.g., in the enantioselective synthesis of 10-oxa-l 1-methyl PGE2 analogues22. This synthesis starts with 1,4-addition of the sulfone-stabilized anion from 27 to ( + )-(S )-4-methyl-2-buteno-lide which has been prepared in three steps from (—)-(S)-l,2-epoxypropane. The intermediate enolate 28 is reacted with the acetylenic iodide to give the trisubstituted diastereomeric mixture of lactones 29, which is eventually converted into the pure compound 30, both reactions occurring with high diastereoselectivity. 

From oxidative cleavage of 1,2-diols and 1,2-amino alcohols Dibutyltin oxide, 95 By reaction of alkyl halides with sulfur-stabilized carbanions Methylthiomethyl p-tolyl sulfone, 192 From reduction of carboxylic acids Vilsmeier reagent, 341 From terminal alkenes by addition reactions... 

Sulfur in its higher oxidation states (e.g., sulfone, —S02—) is especially effective in stabilizing adjacent carbanion centers. However, from a synthetic standpoint there are disadvantages to the sulfone grouping in that the better stabilized carbanions also are the least reactive, and subsequent removal of the sulfone grouping can be difficult. A good balance between carbanion stability, carbanion reactivity, and ease of C-S bond cleavage is present in the... 

Olefin synthesis. Condensation of aldehyde tosylhydrazones with stabilized carbanions affords alkenes by an addition-fragmentation process. The overall sequence is formulated in equation (I). Functional groups such as sulfides, sulfones, thioacetals, hemithioacetals, and nitriles can serve as Y, the anion stabilizing group in 2 and the leaving group in 3. When Y = SO2R, the anions 1 and 2 are conveniently prepared by treatment of a mixture of the tosylhydrazone and sulfone with LDA in... 

The reaction of the stabilized carbanion derived from a-phenylselanylmethyl phenyl sulfone with an acylsilane allowed the synthesis of E/Z mixtures of... 

The importance of sulfones (R SO ) lies in the stabilization that they provide to adjacent carbanions. The carbanions are produced by treatment of the sulfone with a strong base such as butyl-lithium or lithium diethylamide. The sulfone a-carbanions may be alkylated and a variety of products may be formed. Once the sulfone has fulfilled its role in a synthetic sequence, it may be removed either by elimination as sulfur dioxide or by reductive cleavage using sodium amalgam. 

There are many examples of BF3-OEt2 promoted openings of (1) by carbanions, including sulfone-stabilized anions, vinylic anions, allylic anions, and phosphonate-stabilized anions. For example, the lithium anion of trans-1,2-Bis(tributylstannyl)ethylene opens (5)-(l) in the presence of BF3-OEt2 in THF at —78°C, affording fra/w-l-(tributylstannyl)-5-tosyl-4-hydroxypent-l-ene in 50% yield the latter is converted into oxirane (3) in 76% yield on treatment with powdered Sodium Hydroxide in monoglyme. ... 

Some sulfur-centered functions and a nitro group which are primarily required for stabilizing the anion, are also capable of serving as the leaving group. Thus, sulfonimidoyl-stabilized carbanions, 25, transfer methylene as well as alkylidenes to Michael acceptors (equation 87)" °. Phenyl sulfones (X = S02Ph in equation 85)" and nitromethane... 

There has been much synthetic interest in sulfiir-stabilized carbanions. Hiese anions include sulfides, 1,3-dithianes, sulfoxides, sulfones and sulfoximides. Since the structural results in this area have been recently compiled and discussed in excellent detail by Boche, it will suffice to present only the list of compounds in Table 5 whose structures have been reported. Most of these anions have varied and unique... 

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