Sulfones, vinyl deprotonation

A review on the reactivity of sugar-derived acyclic sulfones has appeared, and describes conjugate additions, desulfonations, vinyl deprotonation, allylic transposition and dipolar cycloaddition reactions ... 

Deprotonation of the vinylic proton is a serious side-reaction in the conjugate addition of organometallic reagents to y-siloxy-a, /J-unsaturated sulfones (89)63b. The use of the... 

There are a number of procedures for coupling of terminal alkynes with halides and sulfonates, a reaction that is known as the Sonogashira reaction.161 A combination of Pd(PPh3)4 and Cu(I) effects coupling of terminal alkynes with vinyl or aryl halides.162 The reaction can be carried out directly with the alkyne, using amines for deprotonation. The alkyne is presumably converted to the copper acetylide, and the halide reacts with Pd(0) by oxidative addition. Transfer of the acetylide group to Pd results in reductive elimination and formation of the observed product. 

Metalated vinyl ethers are configurational stable up to —20°C in tetrahydrofuran. H-NMR measurements of 1-ethoxy-1-lithioethene TMEDA did not show any coalescence of the signals for the vinyl protons until the onset of decomposition. Thus, there is no evidence of inversion in this case . Similar configurational stability is displayed by a-lithiated thioethers in tetrahydrofuran no inversion occurs up to 0°C. On the contrary, deprotonated vinyl sulfoxides and sulfones are configurationally less stable . ... 

The Pandey group has developed a silver fluoride-promoted desily lation of tertiary bis(silyl)amines as an interesting alternative method to access azomethine ylides (Scheme 2.10).18 Notably, this method allows the generation of nonstabilized azomethine ylides under essentially neutral conditions. The starting materials are prepared by a three-step process, sometimes coupled into a single operation. For example, Boc-protected pyrrolidine 36 can be sequentially deprotonated and silylated twice in a one-pot reaction (Scheme 2.10). Removal of the Boc group and alkylation of the free amine leads to bis(silyl)amine 37. When this compound is treated with 2 equiv of silver fluoride in the presence of phenyl vinyl sulfone, rapid formation of products 39 as single stereoisomers results. 

Electrophilic additions to vinyl sulfoxides and sulfones allow for further functionalization of these compounds at the a-position. Deprotonation of the a-hydrogen, under appropriate conditions, gives rise to a-vinyl anions which can be trapped by electrophiles. This protocol has been employed in the synthesis of a diverse range of compounds, such as 34 and 37, 40 and 43, and 46 (see Schemes 9, 10, and 11, respectively). Both enantiomers of optically pure propargylic alcohols (115) were conveniently prepared by the reaction of the a-vinyl anion of 2-(trimethylsilyl) vinyl... 

Phenyl vinyl sulfide possesses a number of synthetically useful attributes. It participates as an electron-rich alkene in 1 +2,2 2+2,3 3+2,4 and 4+25 cycloaddition reactions. Deprotonation of phenyl vinyl sulfide with strong base affords an a-metallated sulfide that reacts with electrophiles.6 The metallation-electrophile sequence and the cycloaddition reactions afford products amenable to further synthetic manipulation via the sulfide functionality. Furthermore, phenyl vinyl sulfide is a convenient precursor to the synthetically useful phenyl vinyl sulfoxide and phenyl vinyl sulfone.7... 

An interesting variation upon these approaches was published by Ley and coworkers. In studies directed toward the synthesis of milbemycin 3i, a vinyl sulfone (43 was deprotonated to form the diene... 

Thioethers (sulfides)319 can be converted to their a-carbanion derivative (296, M = Li, Na, K) by treatment with strong bases such as -butyllithium, sodium amide (NaNH2) or potassium amide (KNH2). The hydrogen atom a-to the sulfur atom of sulfides is a weaker acid than that a-to a carbonyl, nitrile or nitro group and stronger bases are required for deprotonation. Sulfides are stronger acids, than the allylic, vinyl, and aromatic hydrocarbons discussed above, however. The various oxides of sulfur can also be converted to a-carbanions. The most important derivatives are the a-carbanions derived from sulfoxides (297). sulfones (298), and... 

Q -monoamon is more reactive and more basic 12.5). When fully substituted at a the deprotonation of phenylsulfonyl methyl sulfones at a also initiates the Ramberg-Backlund rearrangement with loss of phenylsulfinate ion. When no a -CH is available for deprotonation, treatment with base serves to eliminate triflinate, as in eq 6, and is also used to create cyclic vinyl sulfones when the a-dialkylation is done with a,ffii-dihalides. ... 

The most prominent use of ketenes is for [2 + 2] cycloaddition with imine for the construction of /3-lactam skeleton. When the Y group in Scheme 1 is vinyl or aryl group, the deprotonation of the activated a-proton is highly facilitated. In this context, the carbonylation of some allylic derivatives, for example, allyl bromide, allyl acetate, allyl phenyl ether, allyl methyl carbonate, allyl phenyl sulfone, and allyl phosphate, documented to form TT-allylpalladium intermediates is examined. It is interesting to note that only phosphate undergoes the cycloaddition to produce /3-lactam. The characteristic dependency of the stereochemistry on the reaction conditions, being contrary to the results in the usual base-induced cycloaddition is also intriguing. Scheme 2 presents the... 

The intense fragment ions arising from amino acid (e.g., prominent fragment ions at m/z 80, 107, and 124, corresponding to sulfur frioxide (SOg"), vinyl-sulfonic acid, and taurine, respectively, are yielded from deprotonated A-acyl taurine). 

A ring closure similar to that yielding a,]3-epoxysulfones (Eq. 13.16) is expected in the phase transfer reaction of phenyl vinyl sulfone with a-chloropropionitrile. Under basic conditions, the nitrile is deprotonated and then adds in the Michael sense to the a,j3-unsaturated sulfone. Protonation of the intermediate a-sulfonylcarbanion yields the simple Michael adduct, (Eq. 13.17), whereas intramolecular nucleophilic substitution would lead to sulfonylcyclopropanes (Eq. 13.18). The former process is favored over the latter to such an extent that less than a 10% yield of cyclopropanes are isolated in this reaction [27]. 

As depicted in Scheme 3.19, Giese et al. had to face such a problem during the course of the total synthesis of Sopharen Ai, [75]. Deprotonation of 99 led rapidly, by competitive elimination, to vinyl sulfone 100, and no coupling between 98 and 99 was observed (reaction 3.19). Reversing the sequence (reaction 3.20) solved the problem and the expected adduct 103 was obtained in 35% yield. 

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