Sulfoxide, alkyl

Cyclodextrins, toroidal molecules composed of 6, 7 and 8 D-glucose units, are now commercially available at reasonable cost. They form inclusion compounds with a variety of molecules and often differentially include sulfoxide enantiomers29,30. This property has been used to partially resolve some benzyl alkyl, phenyl alkyl and p-tolyl alkyl sulfoxides. The enantiomeric purities after one inclusion process ranged from 1.1 % for t-butyl p-tolyl sulfoxide to 14.5% for benzyl r-butyl sulfoxide. Repeating the process on methyl p-tolyl sulfoxide (10) increased its enantiomeric purity from 8.1% to 11.4% four recrystallizations raised the value to 71.5%. The use of cyclodextrins in asymmetric oxidations is discussed in Section II.C.l and in the resolution of sulfmate esters in Section II.B.l. 

III. REACTIONS OF ELECTROPHILES WITH a-SULFINYL CARBANIONS A. Carbanions from Alkyl Sulfoxides... 

A major problem with the sulfoxide synthesis using menthyl sulfmates is its failure to produce optically pure dialkyl sulfoxides. The prerequisite menthyl alkanesulfinates are oils which have resisted separation into the individual epimers. The menthyl phenyl methanesulfmates are an exception the R epimer is crystalline . One solution to this problem, at least for preparing methyl alkyl sulfoxides, was achieved using cholesteryl methanesulfmates (27) . Both epimers were crystalline and could be separated by fractional crystallization, although in poor yield. Treatment of the epimers with n-propyl, n-butyl, isobutyl, p-tolyl and benzyl magnesium halides yielded the respective methyl alkyl sulfoxides (28) in greater than 95% e.e. and in 32 to 53% yields. 

Scheme 3.34 2,2 -Bipyridine alkyl sulfoxide ligands for addition of ZnEt2 to benzaldehyde.

In 2008, Rykowski et al. reported the synthesis of optically active 2,2 -bipyridine alkyl sulfoxides by asymmetric oxidation of their corresponding readily accessible 2,2 -bipyridine alkyl sulfides. These sulfoxides were further evaluated as ligands for the enantioselective addition of ZnEt2 to benzaldehyde, providing only low enantioselectivities of up to 14% ee (Scheme 3.34). 

Alkyl-substituted silicon peroxides, 78 444 Alkyl sulfates, 23 537 use in cosmetics, 7 849 Alkylsulfones, O-alkylation and, 9 280 Alkyl sulfoxide, micellization of, 24 132t Alkyl tertiary alkyl ethers, 70 575 Alkylthexylboranes, 73 639 Alkyl-thiols, 77 57 4-Alkylthiosemicarbazides, 73 575 Alkyl-tin catalysts, 20 40 Alkyltitanium halides, 25 108—109 Alkyltitaniums, 25 106 higher, 25 116... 

The thermal racemization of optically active aryl allyl sulfoxides ArS(0)CHjCH=CH2 is orders of magnitude faster, and has a much lower activation energy, than that of aryl alkyl sulfoxides ArS(0)R (Bickart et ai, 1968). The reason is that the presence of the allyl group permits the sulfoxide to equilibrate with the isomeric, achiral sulfenate ester by a concerted, cyclic process (89) for whichis only about 20 kcal moM.The rates of racemiz-... 

Nevertheless, correlations have been found in four j3-hydroxyesters (107), eight aminoesters (108), primary a-deuterioalcohols (109), and secondary carbinols (110). Even in a closely related series, exceptions have been found (110) in search of a predictable pattern. A study of nonequivalence in methyl alkyl sulfoxides with CLSR 54c (48) revealed a diminution of nonequivalence on increasing alkyl bulk with an inversion of sense between n-propyl and isopropyl. Changes in nonequivalence sense in several cases with different CSA-solute ratios were also observed. Presently, these CLSR configurational correlations remain totally empirical. 

An alternative route to enantiomeric methyl alkyl sulfoxides (95) is based on the reaction of aliphatic Grignard reagents with the dia-... 

Methyl alkyl sulfoxides that do not contain other strongly perturbing groups have negative Cotton effects centered at the strong absorption band near 200 nm and have the (i > configuration. 

It must be stressed, however, that the methyl alkyl sulfoxide rule is not valid for alkyl benzyl and alkyl allyl sulfoxides (222-224), where the electronic, steric, and solvent effects exert influences on the chiroptical phenomena in a way that is difficult to rationalize. This rule was found to be satisfactory and was used for the assignment of absolute configurations of steroidal (200,201,225), penicillin (226), and amino acid (227-230) sulfoxides. 

It has recently been shown that alkyl sulfoxides are good solvents for transition metal halides, and many adducts can be isolated 42, 84, 167, 227, 231). Nickel perchlorate takes up six dimethyl sulfoxide ligands, but the chloride apparently only three. It has been shown from the reflectance spectrum and from the high magnetic moment 42) that this compound should be formulated as [Ni(DMSO)6][NiCl4], in which the anion is tetrahedral. Infrared spectra 43, 127) show that the dimethyl sulfoxide coordination is through oxygen. Similar compounds are found with tetrahydro-thiophenoxide 84) ... 

Table 9.5 W03-catalyzed kinetic resolution of aryl alkyl sulfoxides (3) in the presence of (DHQD)2-PYR at 25 °C...

Deoxygenation of sulfoxides.1 This reaction can be carried out with cyanuric fluoride in dioxanc (3-9 hours, 65 80% yield). Cyanuric chloride (3, 72 4, 522 5, 687 6, 149) can be used in the case of aryl sulfoxides, but alkyl sulfoxides undergo Chlorination with this reagent. 

Alkyl sulfoxides undergo thermal (3-elimination to yield alkenes. This strategy for the preparation of alkenes has also been applied to solid-phase synthesis, but only substrates with a high tendency to undergo elimination (e.g., y-oxo sulfoxides) could be thermally released from the support (Entry 5, Table 3.43). Unactivated sulfoxides could not be cleaved, not even under forcing conditions (199°C [767]). 

Recently, Egami and Katsuki developed an effective Fe(salan)-catalyzed oxidation of sulfides with H202 in water (Table 3.12) [168]. The reaction can be carried out using low catalyst loadings (1 mol%) in air and at room temperature (20 °C). High yields and enantioselectivities (81-96% ee) were achieved not only for alkyl aryl sulfoxides but also for alkyl alkyl sulfoxides. 

Lower members of the series of salts formed between organic sulfoxides and perchloric acid are unstable and explosive when dry. That from dibenzyl sulfoxide explodes at 125°C [1], Dimethyl sulfoxide explodes on contact with 70% perchloric acid solution [2] one drop of acid added to 10 ml of sulfoxide at 20° C caused a violent explosion [3], and dibutyl sulfoxide behaves similarly [4]. A fatal explosion resulted from mistakenly connecting a DMSO reservoir to an autopipette previously used with perchloric acid [5], (The editor has met a procedure for methylthiolation of aromatics where DMSO was added to excess 70% perchloric acid he did not feel justified in trying to scale it up.) Explosions reported seem usually to result from addition to excess sulfoxide. Aryl sulfoxides condense uneventfully with phenols in 70% perchloric acid, but application of these conditions to the alkyl sulfoxide (without addition of the essential phosphoryl chloride) led to a violent explosion [4]. Subsequent investigation showed that mixtures of phenol and perchloric acid are thermally unstable (ester formation ) and may decompose violently, the temperature range depending on composition. DSC measurements showed that sulfoxides alone... 

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