Sulfones, deprotonation

An attractive flexibility in using anomeric phenyl sulfones is that a stereodivergent synthesis of C-glycosides is available by alkylation before the reductive desulfonylation event. Thus, a one-pot four-step sequence of sulfone deprotonation-electrophile quenching-reductive lithiation-methanol quenching on sulfone 14 provides stereoselectively P-C-glycosides 19 as shown with aldehyde 16 (Fig. 

A complicated example involves the following deoxyglucosylsulfone. Even with variable a/ji ratios of the sulfone, deprotonation and deuteration yields the same product ratio (a//f 1 4). Most importantly for preparative purposes, this mixture of epimers yields only the S-(equato-rial)-deuterated isomer 9 on reductive desulfonation57. 

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. 

Section 15 13 Thiols are compounds of the type RSH They are more acidic than alco hols and are readily deprotonated by reaction with aqueous base Thiols can be oxidized to sulfemc acids (RSOH) sulfimc acids (RSO2H) and sulfonic acids (RSO3H) The redox relationship between thiols and disul tides IS important m certain biochemical processes... 

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... 

Introduction of the phenylthio group onto the 5-carbon atom of alcohols can have valuable synthetic applications. 5-Phenylthio alcohols can be oxidized to the corresponding 5-sulfoxides and sulfones (with their versatile reactivities) or they can be deprotonated by strong base converting the 5-carbon atom to a nucleophilic species. Conversion of 5-phenylthio alcohols to the corresponding 5-carbonyl compounds can be achieved via halogenation followed by subsequent hydrolysis. In this way an inversion of the reactivity of the 5-carbon atom may be accomplished and it can react as an electron acceptor. 

Thioethers (sulfides) can be prepared by treatment of alkyl halides with salts of thiols (thiolate ions). The R group may be alkyl or aryl and organolithium bases can be used to deprotonate the thiol. As in 10-37, RX cannot be a tertiary halide, and sulfuric and sulfonic esters can be used instead of halides. As in the Williamson... 

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. 

In sulfonation on the other hand, a tritium isotope effect is observed.287 Sulfonation is a reversible reaction and the fact that it is less exothermic is compatible with a slow, rate-determining dissociation of the intermediate. The transition state for the slow second step has a less covalent carbon-hydrogen bond than the ground state and hence the reaction is faster for deprotonation than for detritonation. 

The reaction of PhS02 with 2-(2 -phenylsulfonyl)-2, 3 -butadienylmalonate 233 affords the five-membered cyclic alkenyl sulfone 235 via a 1,4-addition, intramolecular deprotonation and a SN2 -substitution process [124, 125]. 

The aqueous cores of reverse micelles are of particular interest because of their analogy with the water pockets in bioaggregates and the active sites of enzymes. Moreover, enzymes solubilized in reverse micelles can exhibit an enhanced catalytic efficiency. Figure B4.3.1 shows a reverse micelle of bis(2-ethylhexyl)sulfosuccinate (AOT) in heptane with three naphthalenic fluorescent probes whose excited-state pK values are much lower than the ground-state pK (see Table 4.4) 2-naphthol (NOH), sodium 2-naphthol sulfonate (NSOH), potassium 2-naphthol-6,8-disulfonate (NSOH). The spectra and the rate constants for deprotonation and back-recombination (determined by time-resolved experiments) provide information on the location of the probes and the corresponding ability of their microenvironment to accept a proton , (i) NDSOH is located around the center of the water pool, and at water contents w = [H20]/[A0T] >... 

In further studies on thiabenzenes, Mislow and co-workers (170) demonstrated that deprotonation of optically active 2-chloro-lO-(2,5-xylyl)-10 thioxanthenium perchlorate 132, resolved via the (+> camphor-10-sulfonate salt, affords optically active 2-chloro-10-(2,5-xylyOthiaanthracene 133, which subsequently rearranges to the corresponding 9-substituted thioxanthene. 

Thermodynamic equilibrium constant for amine deprotonation Thermodynamic equilibrium constant for thiol sulfonate protonation... 

A further eight steps were required to convert the cyclopentanone 52 into the sulfone 59 that was deprotonated and treated with an allylic bromide (60) to afford the alkylated sulfone 61 (Scheme 7). The sulfone moiety and the benzyl ether protecting group were reductively removed in a one-pot procedure to afford a mono-protected diol (62). 

The sulfone moiety was reductively removed and the TBS ether was cleaved chemoselectively in the presence of a TPS ether to afford a primary alcohol (Scheme 13). The alcohol was transformed into the corresponding bromide that served as alkylating agent for the deprotonated ethyl 2-(di-ethylphosphono)propionate. Bromination and phosphonate alkylation were performed in a one-pot procedure [33]. The TPS protecting group was removed and the alcohol was then oxidized to afford the aldehyde 68 [42]. An intramolecular HWE reaction under Masamune-Roush conditions provided a macrocycle as a mixture of double bond isomers [43]. The ElZ isomers were separated after the reduction of the a, -unsaturated ester to the allylic alcohol 84. Deprotection of the tertiary alcohol and protection of the prima-... 

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 . ... 

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