Chiral sulfite

In 1952 Herzig and Ehrenstein (141) obtained chiral sulfites for the first time. They found that a mixture of the cyclic diastereomeric sulfites 95, separated by chromatography, is obtained on treatment of 3-(3-5,19-trihydroxyetiocholanate 96 with thionyl chloride in the... 

Pritchard and co-workers (147) reported the preparation of an acyclic chiral sulfite, 98, which is formed as a mixture of diastereo-mers in the reaction between racemic methyl chlorosulfite and (+)-diphenacyl malate. The pure diastereomers of 98 were isolated by fractional crystallization. 

A very interesting method for the synthesis of chiral sulfites with the sulfur atom as the only chiral center was reported by Reid and... 

Asymmetric synthesis of sulfoxides from chiral sulfite 1 (ref. 28)... 

Rebi re, F. Samud, O. Ricard, L and Kagan, H. B. (1991) A general route to enantiomerically pure sulfoxides from a chiral sulfite, /. Org, Chem. 56,5991-5999. 

The Mikolajczyk group36 has developed use of natural alkaloids as chiral catalysts in conversion of symmetrical dialkyl sulfites into alkyl t-butylsulfinate esters in 40-70% enantiomeric purity (equation 6). 

Although the Sharpless asymmetric epoxidation is an elegant method to introduce a specific defined chirality in epoxy alcohols and thus, in functionalized aziridines (see Sect. 2.1), it is restricted to the use of allylic alcohols as the starting materials. To overcome this limitation, cyclic sulfites and sulfates derived from enantiopure vfc-diols can be used as synthetic equivalents of epoxides (Scheme 5) [12,13]. 

C-chiral racemic y-hydroxy sulfides were also resolved using PEL under kinetic resolution conditions. The products were transformed into optically active 3-(alkanesulfonyloxy)thiolane salts (Scheme 1). Similarly, 1,2-cyclic sulfite glycerol derivatives cis and trans) were resolved into enantiomers via a Pseudomonas cepacia-catalysed acylation with vinyl butyrate. The E values depended on the solvent used and varied from 2 to 26. ... 

Mikolajczyk and coworkers have summarized other methods which lead to the desired sulfmate esters These are asymmetric oxidation of sulfenamides, kinetic resolution of racemic sulfmates in transesterification with chiral alcohols, kinetic resolution of racemic sulfinates upon treatment with chiral Grignard reagents, optical resolution via cyclodextrin complexes, and esterification of sulfinyl chlorides with chiral alcohols in the presence of optically active amines. None of these methods is very satisfactory since the esters produced are of low enantiomeric purity. However, the reaction of dialkyl sulfites (33) with t-butylmagnesium chloride in the presence of quinine gave the corresponding methyl, ethyl, n-propyl, isopropyl and n-butyl 2,2-dimethylpropane-l-yl sulfinates (34) of 43 to 73% enantiomeric purity in 50 to 84% yield. This made available sulfinate esters for the synthesis of t-butyl sulfoxides (35). 

O-Alkylation of 4-hydroxy-3-morpholino-l,2,5-thiadiazole 132 has been achieved with the chiral cyclic chloro-methyl sulfite 133 which subsequently suffers ring opening on treatment with simple alcohols <2001RCB436> or alkylamines <2002RJ0213> to afford the timolol analogues 134 with very little racemization (Scheme 20). This indicated an almost exclusive attack of the oxy anion on the exocyclic carbon atom and is a significant improvement on the previous oxirane method, which suffers from racemization. An alternative biocatalytic asymmetric synthesis of (A)- and (R)-timolol has also appeared <2004S1625>. 

NMR spectral differentiation of enantiomers as solutes in chiral solvents has been achieved with sulfoxides, sulfinates, thiosulfinates, sulfinamides, and sulfites (86,108,242). The usefulness and high sensitivity of this method is confirmed by its successful application... 

Xlld does not involve the chiral center, so if the reaction takes place by this pathway, the migration of the alkyl group from sulfur to palladium (with the concomitant or subsequent loss of sulfur dioxide) must take place with inversion of configuration at carbon. Inversion of configuration at carbon has been observed in the reverse-type reaction, the sulfur dioxide insertion into a carbon-iron sigma bond (49). Nucleophilic displacement at carbon in compounds of type Xld is unusually difficult, so the reaction via the sulfite intermediate Xlld would appear to be more likely. Conversion of the tosylate of l-phenyl-2,2,2-trifluoroethanol to the corresponding chloride, a reaction which takes place in the presence of tetra- (n-butyl) ajnmonium chloride with inversion of configuration at carbon, requires 100°C for 24 hrs in dimethylsulfoxide. 

Chiral amino alcohols and diamines. The chiral vtc-diols available by catalytic asymmetric dihydroxylation of alkenes (14, 237-239) can be converted via a derived cyclic sulfite into chiral 1,2-amino alcohols and diamines as shown in equation I. The same transformations are useful in conversion of 1-alkyl- or arylethane-1,2-diols into the corresponding amino alcohols and diamines. 

Chiral sulfinates, (CH3)3CS(0)0R. Alkyl f-butylsulfinates can be prepared by reaction of /-butylmagnesium chloride with dialkyl sulfites. If the reaction is carried out in the presence of an optically active amine, the products can be optically active. The highest enantioselectivity is observed with amino alcohols, in particular with (-)-quinine (1). 

Chiral cyclic sulfites in asymmetric synthesis of sulfoxides 91PS(58)89. 

Synthesis of chiral sulfoxides through 5-membered cyclic sulfites of ethyl lactate 91PS(56)89. 

This is the second important contribution of Kagan s group in the synthesis of chiral sulfoxides. The method was reported in 1989 for the synthesis of tert-butyl sulfoxides,90 and the full paper on the generalization of the method was published in 1991.86 The approach is based on the synthesis and use of an o.p. cyclic sulfite in the synthesis of various sulfoxides by two successive condensations of two organometallic reagents, RjM and R2M. Thus, the sulfoxides are produced in three separate steps the formation of cyclic sulfite, synthesis of sulfinate esters, and transformation of sulfinates to chiral sulfoxides. 

The chiral diol 5291 (Scheme 15), obtained from ethyl tartrate in one step (75%), was used to obtain the intermediate five-membered ring cyclic sulfite. The reaction... 

Table 11. Synthesis of Chiral Sulfinates 55 and 56 from Sulfite 53 (Scheme 16)...

However, this method suffers severely from the tedious experimental conditions leading to the sulfoxides from diol 52. Several crystallizations are required—the first to purify the tnms sulfite, a second to purify the hydroxy sulfinate, and, finally, a column chromatography to purify the sulfoxide. This may be the reason why there is no application of this method in the literature, apart from that by the same group in the sulfinylation of ferrocene,94 getting the o-lithium derivative to react with various electrophiles to afford chiral ferrocenes (Scheme 17,59 R = HOCMe2, Me, Ph2P). 

Other chiral sulfinyl transfer reagents include a cyclic sulfite (1) [16] and sulfinamides (2) and (3) [17,18],... 

Oppolzer s camphor sultam, a well known chiral auxiliary, has been applied to the asymmetric synthesis of chial fluorine-containing amino acids <07OL2513>. Photoinduced addition of perfluoroalkyl iodides 189 to /V-acyloylcamphorsultam 188 in the presence of an aqueous solution of sodium sulfite provides alkyl iodides 190 with moderate to good stereoselectivities. Azide displacement with the major diastereomer of 190 proceeds with inversion of configuration. Subsequent removal of the sultam auxiliary and hydrogenation of the azide afford the chiral fluorine-containing amino acid 192. 

The typical S-oxidation with BVMOs allows the formation of chiral sulfoxides from organic sulfides. This oxidation has received much interest in organic chemistry due to its use in the synthesis of enantiomerically enriched materials as chiral auxiliaries or directly as biologically active ingredients. This reaction has been studied extensively with CHMO from Adnetohacter showing high enantioselectivi-ties in the sulfoxidation of alkyl aryl sulfides, disulfides, dialkyl sulfides, and cychc and acyclic 1,3-dithioacetals [90]. CHMO also catalyzes the enantioselective oxida-hon of organic cyclic sulfites to sulfates [91]. 

Preparation of Chiral Sulfinates. Optically active sulfinates can be prepared by reaction of a symmetrical sulfite with t-Butylmagnesium Chloride in the presence of an optically active amino alcohol. The best enantioselectivity has been observed using quinine as the optically active amine (eq 2)3 An alternative approach to this new enantioselective asymmetric synthesis of alkyl t-butylsulfinates would be reaction of a racemic sulfinate with r-butylmagnesium chloride complexed by optically active alkaloids (eq 3). In this case, kinetic resolution of the racemic sulfinate leads to an optically active sulfinate and an optically active sulfoxide. 

Nonetheless, much excellent use has been made of this system. Receptor 5, for example, extracts p-nitrobenzoate quantitatively from water into chloroform (43), and the chirality of the receptor allows the possibility of chiral anion recognition (44). Guanidinium has also been incorporated into devices, such as a hydrogen sulfite selective electrode (45). Recently, Mendoza and co-workers (46) reported a chiral double helical array of polyguanidinium strands assembled around sulfate templating anions, the first anion centered helical structure. 

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