Reactions with sulfonyl-stabilized carbanions

The Julia olefination involves the addition of a sulfonyl-stabilized carbanion to a carbonyl compound, followed by elimination to form an alkene.277 In the initial versions of the reaction, the elimination was done under reductive conditions. More recently, a modified version that avoids this step was developed. The former version is sometimes referred to as the Julia-Lythgoe olefination, whereas the latter is called the Julia-Kocienski olefination. In the reductive variant, the adduct is usually acylated and then treated with a reducing agent, such as sodium amalgam or samarium diiodide.278... 

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... 

The stabilized carbanion a to a sulfonyl group has been used mainly for carbon-carbon bond-forming purposes by reactions with electrophiles [109, 110, 386]. Their importance is based on the efficiency of their preparation, of their use particularly for alkylation procedures and on the elaboration of reliable methods for sulfonyl group elimination. One example is shown here, with a synthesis of fl//-trans-squalene [396] close to the Biellman synthesis (see Section 4.2.1.4). 

When chloromethyl phenyl sulfone (130 Ar = phenyl) was subjected to the Darzens-type reaction with an aldehyde, a thermodynamically stable trans isomer (133) was produced exclusively (equation 32). This is in sharp contrast with the corresponding reaction of chloromethyl phenyl sulfoxide. Tavares proposed that the initial nucleophilic attack of the a-sulfonyl carbanion upon a carbonyl compound is rapidly reversible due to its stability, and that the product-determining step is the ring closure. Thermodynamic equilibrium between the two diastereomers of (132) allows predominant formation of the thermodynamically stable isomer (133) from the preferred transition state. ... 

Similar condensations can be accomplished with other types of stabilized carbanions, e.g. sulfonyl anions, as illustrated by equation (81). The resulting sulfonyl lactone (228) eliminates sulfinic acid on treatment with p-TsOH to furnish the a,3-unsaturated system (229).Spirolactonization is the result of the Reformatsky reaction of ester (231) with cyclic ketones. In equation (82), this reaction is applied to the synthesis of the lysergic acid precursor (232), which is formed stereoselectively from (230). ... 

In its original form,94 the Julia reaction consisted of the formation of a carbon-carbon double bond through the coupling of a sulfonyl-stabilized anion and a carbonyl compound to generate a P-hydroxy sulfone, followed by a reductive elimination to afford the alkene (Eq. 47). A subsequent study of its scope and stereochemistry led to improved reaction conditions, which are now widely used.206 Alternative methods to synthesize the P-hydroxy sulfone intermediates, such as the addition of sulfonyl carbanions to esters with subsequent reduction of the ketone to the P-hydroxy sulfone, are also known (Eq. 121).207... 

In l-hthio vinyl sulfides (sec. 8.6) the sulfur atom stabilized the carbanion, allowing either alkylation or condensation reactions. The sulfonyl moiety can also stabilize a vinyllithium derivative. Vinyl sulfone (321), for example, was converted to the 1-lithio derivative with methyllithium.332 xhis organometallic reacted in the usual manner with alkyl halides (methyl iodide) to give the coupling product, 322. 

A variety of functionalized alkenes has been directly obtained with E selectivity from the Homer-Wittig reaction of aldehydes (or ketones) with phosphine oxide-stabilized carbanions bearing in the a position certain functional groups such as aryl [197], vinyl [198-200], cyano [201], sulfonyl [202], isoxazole [203], amino [204], or alkylthio [205]. The functional group provides stabilization for the negative charge of the p-oxido phosphine oxide intermediate and lowers the activation energy for the elimination step to form an alkene (Scheme 42). 

In the Horner-Emmons reaction (Scheme 3), the sulfonylphosphonate carbanion 5 is formed in the presence of NaH and then reacts with an aldehyde to produce the intermediate 6 that undergoes in situ elimination to yield the vinyl sulfones and phosphonate anion. The sulfonyl group can stabilize the anion in the sulfonylphosphonate 5. The vinyl sulfones that are produced by this method using aldehydes as starting materials are exclusively the E (trans) isomers. The E-isomers of the vinyl sulfones are shown in the NMR spectra based on the coupling constants of the vinylic protons. Although strongly basic conditions are used in the Horner-Emmons reaction and a-amino aldehydes are easily racemized, the amino acid vinyl sulfones prepared by this method still show substantial optical activity. However, the enantiomeric purity of these compounds has not been determined. 5 ... 

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-... 

Reactions that proceed by the Elcb mechanism are limited to reactants having substituent groups that can effectively stabilize the intermediate carbanion. This mechanism is not observed with simple alkyl halides or sulfonates. It is more likely to be involved when the leaving group is j8 to a carbonyl, nitro, cyano, sulfonyl, or other carbanion-stabilizing group. 

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