Sulfoxides, vinyl optically active

An optically active sulfoxide may often be transformed into another optically active sulfoxide without racemization. This is often accomplished by formation of a new bond to the a-carbon atom, e.g. to the methyl carbon of methyl p-tolyl sulfoxide. To accomplish this, an a-metallated carbanion is first formed at low temperature after which this species may be treated with a large variety of electrophiles to give a structurally modified sulfoxide. Alternatively, nucleophilic reagents may be added to a homochiral vinylic sulfoxide. Structurally more complex compounds formed in these ways may be further modified in subsequent steps. Such transformations are the basis of many asymmetric syntheses and are discussed in the chapter by Posner and in earlier reviews7-11. 

Optically active vinyl sulfoxides 6 were also produced from the reaction of 1 (R=H) with(-)-(S)-menthyl sulfinate, via the intermediate formation with in-... 

Alkenyl sulfoxides (42 and 43) were first prepared in optically active form by Mulvaney and Ottaviani , described in an article overlooked by most workers in the field, and a year later by Stirling and coworkers through the reaction of the appropriate vinyl Grignard reagent with sulfinate ester 19. Both groups studied the addition of nucleophiles to the carbon-carbon double bond . More recently, Posner and coworkers reported a similar synthesis of ( )-l-alkenyl sulfoxides, e.g. 44 and In the synthesis of 45,... 

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. 

The reaction of bromine with the optically active (i )-a-methyl-vinyl p-total sulfoxide 322 also yields a mixture of diastereomeric sulfoxides 323 their ratio, estimated by the NMR method, was 71.5 28.5. 

Michael-Additions The most important application of this type of reaction is the carbon-carbon bond formation p to a carbonyl function by the addition of carbanion. The asymmetric version of the Michael-addition has been known since 1973. An optically active vinyl sulfoxide served as chiral auxiliary198). 

Since early investigations about the asymmetric addition of diethyl sodiomalonate to optically active vinylic sulfoxides,100-101 Posner and his coworkers102-117 have developed a highly useful methodology based on the conjugate addition of carbon nucleophiles to homochiral a-arylsulfinyl-a,(J-unsaturated carbonyl compounds. While acyclic derivatives still lead only to moderate results,103 the strength of this method is for cyclic systems. For example, the 2-sulfinyl-2-cycloalkenones (94) and (95), the 2-sulfinyl-2-alkenolides (96) and (97), as well as their respective enantiomers are excellent substrates. All these compounds are quite readily accessible in enantiomeric purities of >98% and are configurationally stable, at least for several months at 0 C. 

Optically active vinyl sulfoxide was prepared by a combination of resolution and elimination reaction. Firstly, inclusion complexation of rac-2-chloroethyl m-tolyl- sulfoxide (118) and 14b in benzene gave, after two recrystallizations from benzene, a 1 1 complex of 14b and (+)-118 of 100% ee in 72% yield. Secondly, treatment of the complex with 10% NaOH gave optically pure (+)-m-tolyl vinyl sulfoxide (119) by HC1 elimination as colorless oil. Rapid polymerization of the (+)-119 proceeded by treatment with BuLi or BuMgBr at -78 °C to give optically active polymer (120). Oxidation of 120 with H2O2 gave optically active polysulfone (121).48... 

The reaction of optically active (l-diethoxyphosphoryl)vinyl p-tolyl sulfoxide (20) with sulfur ylides has provided the corresponding cyclopropanes (21) in high yields (g) (Scheme 10).52,53 With fully deuterated dimethyl(oxo)sulfonium methylide, (CD3)2 S(0)CD2, the cyclopropanation reaction occurred in a highly diastereoselective... 

The structurally related optically active a-acyl vinyl p-tolyl sulfoxide 269 underwent asymmetric cyclopropanation. Michael addition of the carbanion of bromomalonate to 269 and the subsequent intramolecular alkylation yielded the corresponding optically active a-acyl-cyclopropane 271, with a high degree of diastereoselectivity (Scheme 70).142 It was proposed that the stereochemical outcome of the reaction can be rationalized by transition state 270, in which there is chelation of the oxygen atom of the carbonyl and sulfinyl groups to the metal cation. 

Tandem Michael addition and Homer olefination occur when a-phosphorylvinyl sulfoxides react with salicylaldehyde leading to a 3-sulfinyl-277-l-benzopyran. Any optical activity associated with the vinyl sulfoxide is retained in the product <06JOC8818>. 

Asymmetric synthesis of a chroman. Solladie and Moine have effected an en-antiospecific synthesis of the chroman-2-carboxaldehyde 7, a key intermediate in the synthesis of a-tocopherol, from (R)-( +)-l. The phosphonate 2, derived from 1, undergoes a Wittig-Horner reaction with the dimethyl ketal of pyruvaldehyde to afford the optically active vinyl sulfoxide 3. Condensation of the aldehyde 4 with the lithio derivative of 3 affords, after silyl deprotection, the allylic alcohol 5 as the only diastereoisomer. This... 

Scheme 267). A lower selectivity is observed using optically active enol ethers in place of the vinyl sulfoxide. 

The Wittig reaction of an optically active sulfinylphospho-nium ylide was reported to yield only the ( )-vinylic sulfoxides (eq 10). ... 

Vinylic sulfoxides have also been used in asymmetric Diels-Alder reaction.A very high dia-stereoselectivity was observed with optically active sulfmylacrylates. One example is given in Scheme 44. 

This 2,3-sigmatropic shift has been of substantial utility since Evans and Hoffmann realized that allyl alcohols can be obtained by intercepting the sulfenate with thiophilic agents. One possible way of preparing optically active allylic sulfoxides, which started to racemize even at 0 C was the isomerization of the corresponding vinylic sulfoxide followed by the sulfenate rearrangement in the presence of trimethyl phosphite (Scheme 51). ... 

The synthesis of the preceding vinyl amino sulfone offers a very good example of a stereospecific sulfide-directed epoxidation (Scheme 76).Oxidation of optically active sulfide alcohol (12 readily made from epoxycyclopentadiene and resolved) with MCPBA affords the corresponding sulfoxide, which is in equilibrium with the sulfenate ester. Treatment with pyridine hydrobromide and then phenyl disulfide and bromine gives the bromodiol (13), which is simply cyclized to the epoxide with aqueous sodium hydroxide solution (83% overall yield from the sulfoxide). Treatment of the P-epoxy sulfone with DBU followed by in situ silylation with f-butyldiphenylsilyl chloride affords an 86% yield of vinyl sulfone (14). Mesylation of the alcohol moiety followed by immediate treatment with dimethylamine produces the amino vinyl sulfone via a syn Sn2 substitution. ... 

Hoffmann has used an isomerization of readily available aryl vinyl sulfoxides, which can be obtained in optically active form, to study the possibility of generating optically active allyl alcohols by employing chirality transfer from sulfur to carbon. While this synthetic route (Scheme 18) to allylic alcohols generally works well and gives good yields, the optical yields which could be obtained are only satisfactory in some cases, e.g. (/ )-(Z)-sulfoxide (13) gave the (S)-(+)-octenol (14) with greater than 80% optical purity, whereas the (/ )-( 5-isomer (15) yielded only 29% of the (f )-(-)-enantiomer (16 Scheme 19). 

A useful extension of sulfoxide-sulfenate rearrangements exploits the greater stability of allylic vs. vinylic sulfoxides.For example, the Knoevenagel product (202) is deconjugated under the conditions of its formation. This sets the stage for a 2,3-rearrangement in the same pot (equation 66). Optically active condensation products give hydroxy esters (201) with 64-72% 50-80% ee were reported for... 

The anionic polymerization of optically active (+)-or (—)-m-tolyl vinyl sulfoxide ([a]o +486°, —486°) using BuLi or BuLi—(—)-Sp leads to an optically active polymer, 37 [[cx]d +274° to +311° (from (+)-monomer) [cx]d -272° to -310° (from (-)-monomer)]. Oxidation of 37 afforded polymer 38 with an achiral... 

Asymmetric induction in stcreospecific palladium-catalyzed [3 + 2] cycloadditions can also be achieved in conversions of trimethylcncmcthane precursors with homochiral vinyl sulfoxides (e.g., 8)33. After further conversions the products may be converted to optically active cy-clopentanones 10. 

Pummerer rearrangement of the optically active sulfoxide (64) to the 1,3-benzoxathiinone (65) occurs with moderate to good transfer of enantiomeric excess when the reaction is promoted by ethoxy vinyl esters <97TA303>. 

Nitroethene and vinyl sulfoxides have also been employed as ketene equivalents. Nitroethene is an excellent dienophile and oxidation of the initial nitro-adduct gives the corresponding ketone. However, the thermal instability of nitroethene limits its appUcation to cycloadditions with reactive dienes. An attractive feature of vinyl sulfoxides as ketene equivalents is that they can be obtained in optically active form because of the chirality of the sulfoxide group, thus allowing enan-tioselective Diels-Alder reactions. Cycloaddition of p-tolyl vinyl sulfoxide with cyclopentadiene requires heat and gives a mixture of all four (two exo and two... 

The first report on the use of enantiomerically pure sulfinyl dienophiles in Diels-Alder cycloadditions was by Maignan and Raphael [156], who utilized (+)-(R)-p-tolyl vinyl sulfoxide (26a) as an optically active dienophile (Scheme 5.58). A mixture of endo (177a) and (177b) and exo (178a) and (178b) diastereoisomers were formed as a result of poor selectivity. 

The first report of the use of optically active a,P-unsaturated sulfoxides as dipolarophiles was by Koizumi et al. in 1982 [196] and preceded the first report of their use as optically active dienophiles, despite the fact that the vast majority of subsequent work in this area has been in the use of dienophiles in asymmetric Diels-Alder reactions. The 1,3-dipolar cycloaddition between (i )-(+)-p-tolyl vinyl sulfoxide and acyclic nitrones such as (261) gave the major cycloadducts such as (262) (90% de) in 57% overall yield (Scheme 5.85). 

The first enantioselective synthesis of an aflatoxin building block was published in 1993 by Marino (57). He presented a synthesis of 32 in 80% enantiomeric excess and induced the stereospecificity via optically active vinyl sulfoxides (see Scheme 2.14). Catechol (40) was acylated, mono-iodinated and then coupled with chiral vinyl sulfoxide 85 under Stille conditions (- 86). Dichloroketene lactonization under reductive conditions followed by zinc-promoted dechlorination gave the major diastereomer 87. 

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