Bis sulfoxides

Scheme 1.8 Test reaction with C2-symmetric bis(sulfoxides) and monosulfoxide ligands.

Scheme 2.34 Rh-catalysed 1,4-additions of arylboronic acids to cyclic enones with bis(sulfoxides) ligand.

Scheme 5.5 Fe-catalysed Diels-Alder reaction with bis(sulfoxides) ligands.

Treatment of bis(methylthio) derivative 170 with z-chloroperbenzoic acid (MCPBA) gives the bis(sulfoxide) 171 (Equation 13) <2001TL8697, 2005JOC6204>. 

Addition of 1,5-dithiacyclooctane to zeolite CaY in the presence of molecular oxygen results in spontaneous oxidation to mono- and bis-sulfoxides through formation of the corresponding radical cation characterized by ESR and diffuse reflectance of UV-Vis spectroscopy.51... 

A type I one-electron photo-oxidation of methionine-methionine-containing peptides by triplet carboxybenzophenone in air-saturated aqueous solution has been reported the S+ radical cation that is formed then reacts with the other Met-S to form an S-S three-electron complex which reacts with superoxide radical anion before hydrolysis to Met(=0)-Met(=0) bis-sulfoxide. Alternatively, cyclization of the A-terminal NH2 on to the S can occur to give a three-electron S-N complex which can react with superoxide radical anion to give a cyclic sulfonium intermediate. 

Three of four possible stereoisomers are formed. Ratio of R-cis-.S-ds R-trans is given. Bis-sulfoxide is the (desired) major product. 

Dithietanes, dimers of thioketones, are best stabilized by electron withdrawing groups on the ring. They are oxidized to bis-sulfoxide derivatives quite readily, and in at least one case the intermediate dioxide was isolated (Scheme 29) (80AG(E)203). 

It was also found that the Padua reagent was useful for the oxidation of three isomeric bis(methylsulfmyl)benzenes with r-BuOOH, yielding the corresponding almost enantiopure bis-sulfoxides [64]. As mentioned above, the enantioselectivity of the first oxidation was enhanced (Horeau principle), because a minor amount of meso-disulfoxide was formed and separated from the chiral disulfoxide. It was reported that the Orsay reagent with cumyl hydroperoxide oxidized an /V-protected 2-.S -methylindole with moderate enantioselectivity, whereas the Padua protocol afforded the desired sulfoxide with 80% ee [65],... 

With Chiral Sulfoxide/metal Complexes Certain chiral hydroxysulfoxide and bis-sulfoxide are found useful as chiral ligands for the enantioselective Diels-Alder addition of acryloyl... 

Chiral bis-sulfoxides with a C2 symmetry axis can be readily prepared from the known (W)-methyl p-tolyl sulfoxide and commercially available methyl (S)-p-toluenesulfinate. Such chiral ligands are very attractive because of their easy synthesis and their ready availability in both enantiomers from inexpensive starting materials. Their complexes with Fel3 are shown to be good chiral catalysts for asymmetric Diels-Alder reactions [48] (Eq. 8A.26). 

A new C2-symmetric bis-sulfoxide/A-oxide (35 R,R-) promotes allylation of N- benzoylhydrazones with allyltrichlorosilane in up to 76% ee.94... 

Reactivity and selectivity increased as the size of the ring containing the bis-sulfoxide moiety become smaller. Thus, racemic dienophile 78 [80] (Scheme 42) reacts with cyclopentadiene under BF3 catalysis in 10 min at -78 °C, yielding a >25 1 mixture of adducts. In the absence of a catalyst, this dienophile is not able to react with 1-methoxybutadiene at room temperature, whereas this acyclic diene was completely transformed into a > 25 1 mixture of adducts by reaction with compound ( )-79 in 24 h [80]. Both dienophiles are able to react with furan under catalytic conditions. The authors conclude that dienophile 79 is in general more reactive and selective than is 78. 

Racemic diesters 82 (Scheme 42), containing the bis-sulfoxide moiety incorporated into a five-membered ring, have also been used as dialkoxycarbonyl ketene equivalents [82]. They react with cyclopentadiene in 7-12 h at room temperature, affording mixtures of two adducts. The relative configuration of 82 was not unequivocally determined, but it was speculatively assigned on the basis of the conformational preferences of the precursor monosulfoxide and the presumably favored steric course of its MCPBA oxidation. We must point out the unexpectedly similar reactivity of dienophiles 80 and 82, which is very difficult to explain given the increase in the dienophilic reactivity that two ester groups usually induce in ethylenic systems. 

One of the most interesting points that can be deduced from the studies carried out on the bis-sulfoxides is the much lower reactivity of acyclic dienophiles than that of cyclic examples (compare the results obtained from 80 and 75 or those from 82 and 83). The influence of the conformation around the C-S bond (with higher restrictions in cyclic sulfoxides), on the dienophilic character of the double bond in vinyl sulfoxides, emerge as the most likely causes of the observed differences in reactivity (see later). 

It will often be necessary to avoid sulfone formation, and this can be achieved by carrying out the reaction below 50 °C, and using only stoichiometric amounts of hydrogen peroxide.373 For example, 1,4-dithiane can be selectively converted to the mono- and bis-sulfoxide by proper control over the hydrogen peroxide addition rate.374 Azeotropic removal of water by the addition of suitable solvents can also increase selectivity.375 However, if sulfones are required, then elevated temperatures should be used.376... 

In a recent pubhcation the nitrile (EWG = CN) variant [ 126] of this chemistry was performed in water by applying N,N-diethylaminopropylated sihca gel as heterogeneous catalyst [ 128]. Another variant of this reaction sequence, leading to chiral sulfinylated enones, has been developed by Llera [ 129] employing the enantiomerically pure geminal bis(sulfoxide) 208 (Scheme 54). This bis(sulfoxide) was prepared from (-)-p-toluenesulfinic acid menthyl ester [100], as described by Kunieda [130]. Later this procedure was improved to increase the yield from 35 to 91% [13,131]. Treatment of 208 with enolizable aldehydes or ketones, in the presence of piperidine as a base and thiophile, initiated a reaction cascade involving a condensation step (to 210), a proton shift to allylic sulfoxide 211, and a [2,3]-0-shift followed by a piperidine-mediated desulfuration delivering the alcohols 212 as isomeric mixtures. Oxidation of the latter compounds (one of the R = H) led to enantiomerically pure E-y-oxo vinyl sulfoxides 213. 

Scheme 54 Geminal bis(sulfoxide) 208 as chiral methylene-active compound...

Preparative Methods the title reagent can be prepared from commercially available (1,2-benzenedithiol and 1,3-dichloroacetone. After condensation of these reagents in the presence of DMAP, the resulting l,5-benzodithepan-3-one is enantioselectively oxidized to the (/f)-monosulfoxide by modified Sharpless oxidation [cumene hydroperoxide, Ti(0-t-Pr)4] in the presence of (-F)-diethyl tartrate as a chiral ligand. - Subsequent dry ozonation" of the (/f)-monosulfoxide affords (lf ,5f )-bis-sulfoxide 1, having >98% optical purity. Alternative use of (—)-diethyl tartrate in the modified Shaipless oxidation makes possible convenient access to enantiomeric (15,5S)-1. ... 

Purification purification is performed by column chromatography. Since unpurified (l/f,5/f)-bis-sulfoxide 1 is only slightly soluble in the eluent, the following procedure is convenient. The crude material is dissolved in EtOAc and mixed with silica gel (ca. 5 g silica gel per 1 g of crude reagent). After solvent evaporation, the silica gel residue containing 1 is added to the top of the column and eluted with hexane-EtOAc (2 1). 

Introduction. (1/f, 5/ )-2/f-l,5-Benzodithiepin-3(4E0-one 1,5-dioxide (C2-symmetric bis-sulfoxide 1) has been used as a chiral auxiliary for asymmetric desymmetrization of cyclic meso-... 

Acetal Formation Involving C2-Synunetric bis-Sulfoxide and mcio-1,2-DioIs (Step 1). Acetalization of mejo-1,2-diols with this reagent should be conducted with TMSOTf and 2,6-lutidine in dichloromethane below 4 °CP Higher temperatures and prolonged reaction times cause undesirable racemization and decomposition of the reagent. When the reactivity of meso-1,2-diols with the chiral auxiliary is low, acetalization using the mono-TMS ether of mcjo-diols and TMSOTf is recommended. ... 

Diastereoselective Acetal Fission Followed by Benzylation (Step 2). Upon treatment with KHMDS and 18-crown-6 in THF at —78 °C, the acetal from the (/f,/ )-bis-sulfoxide is rapidly converted into the alkoxide having the (lS,2f ) configuration. The counter cation of the base is very important for high selectivity. Diastereoselectivity was seen to increase in the order LiHMDS (8% de) 96% de). 

Oxidation of the 3 -0-benzodithiol-2-yl derivative of thymidine 262 with w-chloroperbenzoic acid (MOPBA) gave the monosulfoxide 263, bis-sulfoxide 264, or bis-sulfonyl derivative 265 (Scheme 31) <2004JME5265>. 

---