Sulfoxides electrophilic additions

Electrophilic substitution of thianthrene takes place at C-2. No examples of even minor amounts of 1-mono-substituted product have been reported. Disubstitution gives 2,7- (usually) or 2,8-products. In a few cases, 2,6-derivatives have been claimed. The presence of a sulfoxide or sulfone unit greatly reduces the susceptibility of either ring to electrophilic substitution. Carbon-centered electrophilic addition to sulfur to produce 5-R-thianthrenium salts has been described rarely most examples of the formation of such salts have involved the thianthrene radical ion(l-t-). Treatment of thianthrene with alkyl/aryllithiums produces the 1-lithio-species, and these organometallic derivatives allow the introduction of substituents at this position. 

There has been extensive research into electrophilic additions to 3-substituted-l,4-dihydropyridines, such as N-methyl-3-cyano-l,4-dihydropyridine 138, which readily undergoes addition across the more reactive enamine-like 5,6-alkene to give 2,3,5-trisubstituted-l,2,3,4-tetrahydropyridines (Scheme 38) <1998JOC2728, 2000CEJ1763, 2003TL8449>. In an unusual example, the reaction with sulfinyl chlorides and triethylamine results in the formation of the 1,4-dihydropyridine sulfoxide 139, where in the absence of an additional nucleophile, the iminium intermediate is deprotonated to yield the monosubstituted 1,4-dihydropyridine product 139. 

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... 

Selenoxide elimination is now widely used for the synthesis of a,p-unsaturated carbonyl compounds, allyl alcohols and terminal alkenes since it proceeds under milder conditions than those required for sulfoxide or any of the other eliminations discussed in this chapter. The selenoxides are usually generated by oxidation of the parent selenide using hydrogen peroxide, sodium periodide, a peroxy acid or ozone, and are not usually isolated, the selenoxide fragmenting in situ. The other product of the elimination, the selenenic acid, needs to be removed from the reaction mixture as efficiently as possible. It can disproportionate with any remaining selenoxide to form the conesponding selenide and seleninic acid, or undergo electrophilic addition to the alkene to form a -hydroxy selenide, as shown in... 

Allylic halogenation of aldehyde enol acetates, e.g. 23, derived from norbornadiene provided an elegant and efficient construction of the tricyclic structure 24 found in many sesquiterpenes such as cyclosativene, cyclocopacamphene, longicyclene, a-santalene and its derivatives. This rearrangement in fact arises from an electrophilic addition to a multiple bond with participation of the homoallylic bond. The tricyclic skeleton was also obtained successfully by treatment of 5-methylenenorborn-2-ene with A-bromosuccinimide in aqueous dimethyl sulfoxide which gave 5-bromo-2-hydroxymethyltricyclo[2.2.1.0 ]heptane (25) in high yield. 

The first report of asymmetric induction in the electrophilic addition to a,P-unsaturated sulfoxides was made by Abbott and Stirling [12,41] who found that treatment of nonracemic (5)-(-i-)-p-tolyl vinyl sulfoxide (26b) with bromine in acetic acid gave the dibromide (30) with ee (a-induction) of 32% and 92% overall chemical yield (Scheme 5.10). (+)-a,P-Methylvinyl p-tolyl sulfoxide gave a higher... 

When enantiomerically pure allyl p-tolyl sulfoxide is deprotonated and then treated with electrophilic 2-cyclopentenone, a conjugate addition occurs forming a new carbon-carbon bond with very high control of absolute stereochemistry (equation 25)65. See also Reference 48. Similarly, using more substituted enantiomerically pure allylic sulfoxides leads to virtually complete diastereocontrol, as exemplified by equations 26 and 27 the double bond geometry in the initial allylic sulfoxide governs the stereochemistry at the newly allylic carbon atom (compare equations 26 vs. 27)66. Haynes and associates67 rationalize this stereochemical result in terms of frontier molecular orbital considerations... 

In contrast to a, -ethylenic ketones or even a, -ethylenic sulfones, a, ) -ethylenic sulfoxides generally are not sufficiently electrophilic to undergo successful nucleophilic j8-addition . a-Carbonyl-a, j8-ethylenic sulfoxides, however, are potent, doubly activated alkenes which undergo rapid and complete -addition of various types of nucleophiles even at — 78 °C. A brief account summarizing this area is available . The stereochemical outcome of such asymmetric conjugate additions to enantiomerically pure 2-sulfmyl 2-cycloalkenones and 2-sulfinyl-2-alkenolides has been rationalized in terms of a metal-chelated intermediate in which a metal ion locks the -carbonyl sulfoxide into a rigid conformation (36 cf. 33). In this fixed conformation, one diastereoface of the cyclic n... 

Due to the high rate of reaction observed by Meissner and coworkers it is unlikely that the reaction of OH with DMSO is a direct abstraction of a hydrogen atom. Gilbert and colleagues proposed a sequence of four reactions (equations 20-23) to explain the formation of both CH3 and CH3S02 radicals in the reaction of OH radicals with aqueous DMSO. The reaction mechanism started with addition of OH radical to the sulfur atom [they revised the rate constant of Meissner and coworkers to 7 X 10 M s according to a revision in the hexacyanoferrate(II) standard]. The S atom in sulfoxides is known to be at the center of a pyramidal structure with the free electron pair pointing toward one of the corners which provides an easy access for the electrophilic OH radical. 

The activation of DMSO toward the addition step can be accomplished by other electrophiles. All of these reagents are believed to form a sulfoxonium species by electrophilic attack at the sulfoxide oxygen. The addition of the alcohol and the departure of the sulfoxide oxygen as part of a leaving group generates an intermediate comparable to C in the carbodiimide mechanism. 

The addition reactions of nucleophilic and electrophilic reagents to optically active a, /3-unsaturated sulfoxides have also been found to proceed in an asymmetric way. Addition of piperidine to chiral (i )-cis-propenyl p-tolyl sulfoxide 309 affords a 87 13 mixture of diastereomeric sulfoxides 310 (318). The configuration at the 3-carbon atom of the predominant diastereomer (i yS )-310 was determined by means of chemical correlation starting from optically... 

The addition of electrophilic reagents to chiral a,/3-unsaturated sulfoxides is also accompanied by asymmetric induction. Stirling and Abbott (318,322) found that the addition of bromine to the optically active (.R)-vinyl-p-tolyl sulfoxide 319 yields a mixture of diastereo-meric a,/3-dibromosulfoxides 320. Oxidation of this mixture gives the optically active sulfone 321, with a center of chirality at the a-carbon atom only. The optical purity (32%) of this sulfone was estimated by comparing its specific rotation with that obtained as a result of oxidation of diastereomerically pure sulfoxide (/ )-320. The assignment of configuration at the a-carbon atom was based on the analysis of the polarizabilities of substituents. 

This procedure was extended to a method for asymmetric synthesis of optically active epoxides starting from optically active sulfoxides. As the oxiranyUithium 131 reacts with the acidic hydrogen of the n-butyl aryl sulfoxide, the introduction of electrophiles to the reaction mixture was problematic. Therefore, the reaction was performed by addition of 1 equivalent of f-C4H9Li at — 100°C to 130 and the sulfoxide-lithium exchange reaction was found to be extremely rapid (within a few seconds at this temperature). Moreover, as f-butyl aryl sulfoxide 138 has now no more acidic hydrogen, the addition of several electrophiles leads to functionalized epoxides 139 (equation 48). ... 

TABLE 6. Synthesis of tetrasubstituted olefins (151) by the reaction of 1-chlorovinyl p-tolyl sulfoxide (147) with ArMgBr followed by addition of electrophiles... 

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