Reversible sulfoxidation reaction

When dissolved in nonpolar solvents such as benzene or diethyl ether, the colourless (2a) forms an equally colourless solution. However, in more polar solvents [e.g. acetone, acetonitrile), the deep-red colour of the resonance-stabilized carbanion of (3a) appears (1 = 475... 490 nm), and its intensity increases with increasing solvent polarity. The carbon-carbon bond in (2a) can be broken merely by changing from a less polar to a more polar solvent. Cation and anion solvation provides the driving force for this heterolysis reaction, whereas solvent displacement is required for the reverse coordination reaction. The Gibbs energy for the heterolysis of (2a) correlates well with the reciprocal solvent relative permittivity in accordance with the Born electrostatic equation [285], except for EPD solvents such as dimethyl sulfoxide, which give larger values than would be expected for a purely electrostatic solvation [284]. 

The metabolism of sulfides (thioethers) is rather straightforward. Besides the S-deal-kylation reactions discussed earlier, these compounds can also be oxygenated by monooxygenases to sulfoxides (reaction 2-A) and then to sulfones (reaction 2-C). Here, it is known with confidence that reaction 2-A is indeed reversible, as documented by many examples of reduction of sulfoxides (reaction... 

Clearly, for symmetry reasons, the reverse process should also be considered. In fact, early versions of our reaction prediction and synthesis design system EROS [21] contained the reaction schemes of Figures 3-13, 3-15, and 3-16 and the reverse of the scheme shown in Figure 3-16. These four reaction schemes and their combined application include the majority of reactions observed in organic chemistry. Figure 3-17 shows a consecutive application of the reaction schemes of Figures 3-16 and 3-13 to model the oxidation of thioethers to sulfoxides. 

Since sulfoxides and sulfones are versatile synthetic intermediates, and since in both the thiolene oxide and dioxides the reverse dethionylation114 ( — SO), and cheletropic extrusion of sulfur dioxide296, respectively, readily take place thermally, these cycloadditions are expected to find a useful place in organic synthesis. It should be kept in mind, however, that the retrograde SO-diene reaction and interconversion of the thiolene oxides compete effectively against SO extrusion on heating, and that diene isomerization accompanies the forward reaction (SO + diene). 

A method for the stereospecific synthesis of thiolane oxides involves the pyrolysis of derivatives of 5-t-butylsulfinylpentene (310), and is based on the thermal decomposition of dialkyl sulfoxides to alkenes and alkanesulfenic acids299 (equation 113). This reversible reaction proceeds by a concerted syn-intramolecular mechanism246,300 and thus facilitates the desired stereospecific synthesis301. The stereoelectronic requirements preclude the formation of the other possible isomer or the six-membered ring thiane oxide (equation 114). Bicyclic thiolane oxides can be prepared similarly from a cyclic alkene301. 

Since its discovery two decades ago, the reversible interconversion of allylic sulfenates to sulfoxides has become one of the best known [2,3]-sigmatropic rearrangements. Certainly this is not only because of the considerable mechanistic and stereochemical interest involved, but also because of its remarkable synthetic utility as a key reaction in the stereospecific total synthesis of a variety of natural products such as steroids, prostaglandins, leukotrienes, etc. 

In addition to the synthetic applications related to the stereoselective or stereospecific syntheses of various systems, especially natural products, described in the previous subsection, a number of general synthetic uses of the reversible [2,3]-sigmatropic rearrangement of allylic sulfoxides are presented below. Several investigators110-113 have employed the allylic sulfenate-to-sulfoxide equilibrium in combination with the syn elimination of the latter as a method for the synthesis of conjugated dienes. For example, Reich and coworkers110,111 have reported a detailed study on the conversion of allylic alcohols to 1,3-dienes by sequential sulfenate sulfoxide rearrangement and syn elimination of the sulfoxide. This method of mild and efficient 1,4-dehydration of allylic alcohols has also been shown to proceed with overall cis stereochemistry in cyclic systems, as illustrated by equation 25. The reaction of trans-46 proceeds almost instantaneously at room temperature, while that of the cis-alcohol is much slower. This method has been subsequently applied for the synthesis of several natural products, such as the stereoselective transformation of the allylic alcohol 48 into the sex pheromone of the Red Bollworm Moth (49)112 and the conversion of isocodeine (50) into 6-demethoxythebaine (51)113. 

Early investigations have indicated that sulfinyl radicals apparently do not add, at least in the usual way, to olefmic double bonds24. However, some recent results by lino and Matsuda25 obtained by studying the thermal decomposition of benzhydryl p-tolyl and benzhydryl methyl sulfoxides in the presence of cis-/2-deuteriostyrene lead one to believe that sulfinyl radicals add reversibly to CH2 =CHPh. The molar ratio of trans to cis /3-deuteriostyrene that they observed at nearly 50% conversion was explained by addition-elimination reaction of sulfinyl radicals. 

As a continuation to the studies by Darwish and Braverman on the [2,3]-sigmatropic rearrangement of allylic sulfinates to sulfones, and in view of its remarkable facility and stereospecificity (see Chapter 13), Braverman and Stabinsky investigated the predictable analogous rearrangement of allylic sulfenates to sulfoxides, namely the reverse rearrangement of that attempted by Cope and coworkers . These authors initiated their studies by the preparation of the claimed allyl trichloromethanesulfenate using the method of Sosnovsky . This method involves the reaction between trichloro-methanesulfenyl chloride and allyl alcohol in ether at 0 °C, in the presence of pyridine (equation 6). 

The C—S bond in the sulfonyl radical RS02 is weak and therefore the reaction of the alkyl radical with the sulfonyl radical is reversible. The decay of the sulfonyl radical is an endothermic reaction. This peculiarity explains the existence of the optimal temperature for sulfoxidation. The increase in temperature lowers the steady-state concentration of sulfonyl radicals and, therefore, increases the chain termination by the reaction of the alkyl radical with dioxygen. 

One of the most interesting reactions in sulfur chemistry is the reversible [2,3]sigmatropic rearrangement of allyl sulfoxides to the corresponding sulfenate esters, which are achiral at sulfur. However, in the case of suitably substituted allyl sulfoxides a new chiral center may be generated at the a-carbon in this process, as shown in eq. [137]. 

As a matter of fact, cosolvents such as primary alcohols, polyols, di-methylformamide and dimethyl sulfoxide are now almost routinely used to perturb the overall reactions and elementary equilibria or rate processes of the highly organized systems carrying out DNA, RNA, and protein synthesis. However, in spite of the fact that such systems respond well and in a reversible way to these perturbations, cosolvent effects remain relatively poor probes of reaction mechanisms (Hamel, 1972 Voigt et al., 1974 Ballesta and Vasquez, 1973 Crepin et ai, 1975 Nakanishi et al., 1974 Brody and Leautey, 1973). The most common result reported upon addition of increasing amounts of cosolvents is a bell-shaped curve equilibria and rate processes are first stimulated and... 

Sulfoxide Reduction Sulfoxide reduction is a two-electron-transfer reversible reaction resulting in thioethers. Organic sulfoxides are used mainly as agrochemicals, and their reduction (abiotic and microbially mediated) has been found in anaerobic soils, sediments, and groundwater (Larson and Weber 1994). 

This enzyme [EC 1.8.4.5], also known as methionine S-oxide reductase, catalyzes the reaction of L-methionine with oxidized thioredoxin to produce L-methionine S-oxide and reduced thioredoxin. Dithiothreitol can substitute for reduced thioredoxin in the reverse reaction. In addition, other methyl sulfoxides can replace methionine sulfoxide in the reverse reaction. 

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