Sulfoxides chiral, preparation

In contrast to asymmetric oxidation of unsymmetrical sulfides with chiral peracids, microbial oxidation usually gives much better results. Thus, optically active phenyl benzyl sulfoxide was prepared by oxidation of the parent sulfide via fermentation with Aspergillus niger, NRRL 337, with 18% optical purity (42). Similarly, asymmetric... 

Diastereoselective reduction of chiral -keto sulfoxides (11,291-292). Chiral p-keto sulfoxides 1, prepared by reaction of p-(tolylsulfinyl)methyllithium with esters, are reduced by DIBAH in THF diastereoselectively to (R,S)-2. In the presence of ZnCl2, the opposite diastereoselectivity obtains. The paper includes a new method for conversion of these p-hydroxy sulfoxides into chiral epoxides.1... 

Similarly, enantiopure 3-substitutcd-/V-rnc thy I benzyl /3-sultams have been converted into A -methylbenzyl-a-amino acid thioesters via sulfenylation and Pummerer rearrangement with high or complete retention of configuration. Chiral sulfoxides were prepared by sulfenylation followed by oxidation of trans-isomers as two separable A and B stereoisomers. Treatment with TFAA gave chiral cr-amino acid thioesters in high yields with a de > 90%. Slight epimerization of the cr-chiral center of the cr-phenyl thioesters has been observed under the reaction conditions whereas no epimerization was observed in the case of -/-butyl thioesters (Scheme 28) <1998JOC8355>. 

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. 

In more recent years, the nucleophilic and electrophilic epoxidations of a-hydroxy dienyl sulfoxides as versatile routes to highly functionalized sulfinyl and sulfonyl tetrahydrofurans have been studied in depth.Fernandez de la Pradilla s group has reported that a-hydroxy dienols bearing chiral sulfoxides (267), prepared from the reaction of chiral dienyl sulfoxide lithium compounds with freshly distilled aldehydes, were subjected to epoxidation using m-CPBA as oxidant, leading to monoepoxides 269 as main products in low to moderate yields and low stereochemical selectivities subsequently, monoepoxides 269 were treated with catalytic CSA to afford 96-99% yields of predominantly 2,5-cis mixtures of sulfonyl dihydrofurans 270 (Scheme 4.86). These highly functionalized sulfonyl tetrahydrofurans were also obtained in a... 

Enantiopure sulfinimines are ammonia imine synthons useful in the asymmetric synthesis of amines and -amino acid derivatives. Sulfinimines unavailable via the Andersen synthesis (R = H) are prepared hy asymmetric oxidation of the sulfenimines, ArS-N=C(R)PhX, with (+)-( ) or (-)-(1) at -20 to 20 °C in CCI4 (eq 8). Crystallization improves the ee to >95%. The sulfoxide chiral recognition model correctly predicts the configuration of the product. 

Asymmetric synthesis has emerged as a major preparative method, widely used in organic chemistry and in the total synthesis of natural products, and which is also of interest for industrial chemistry. The importance of enantiomerically pure compounds is connected with the applications in pharmaceutical industries, since very often the biological activity is strongly linked to the absolute configuration. In this article the historical developments of asymmetric synthesis will be briefly presented, as well as the main methods to prepare enantiomerically enriched compounds. Then recent asymmetric synthesis of two classes of compounds will be discussed i) Sulfoxides, chiral at sulfur ii) Ferrocenes with planar chirality. The last part of the article will be devoted to asymmetric catalysis with transition-metal complexes. The cases of asymmetric oxidation of sulfides to sulfoxides and nonlinear effects in asymmetric catalysis will be mainly considered. 

CHMO.. has been used in the diastereoselective oxidation of different p-hydroxy sulfides to the corresponding chiral p-hydroxy sulfoxides. Chiral p-hydroxy sulfoxides represent interesting compounds used as chiral auxiliaries in asymmetric synthesis, asymmetric ligands, or as building blocks for the synthesis of cyclic sulfides, benzoxathiepines, allylic alcohols, or leukotrienes [27]. The sulfoxidation of these substrates is a kinetic resolution, in which both the sulfide and the sulfoxide can be obtained in chiral form. Oxidation of the cyclohexyl derivative (Table 6.1, entry 2) by a semipurified preparation of in the presence of the enzymatic... 

Louren90 CL, Batista JM, Furlan M, He Y, Nafie LA, Santana CS, Cass QB. Albendazole sulfoxide enantiomers preparative chiral separation and absolute stereochemistry. J. Ckroma-togr., A 2012 1230 61 5. 

Chiral chemical reagents can react with prochiral centers in achiral substances to give partially or completely enantiomerically pure product. An example of such processes is the preparation of enantiomerically enriched sulfoxides from achiral sulfides with the use of chiral oxidant. The reagent must preferential react with one of the two prochiral faces of the sulfide, that is, the enantiotopic electron pairs. 

Sharpless and Masumune have applied the AE reaction on chiral allylic alcohols to prepare all 8 of the L-hexoses. ° AE reaction on allylic alcohol 52 provides the epoxy alcohol 53 in 92% yield and in >95% ee. Base catalyze Payne rearrangement followed by ring opening with phenyl thiolate provides diol 54. Protection of the diol is followed by oxidation of the sulfide to the sulfoxide via m-CPBA, Pummerer rearrangement to give the gm-acetoxy sulfide intermediate and finally reduction using Dibal to yield the desired aldehyde 56. Homer-Emmons olefination followed by reduction sets up the second substrate for the AE reaction. The AE reaction on optically active 57 is reagent... 

Racemic mixtures of sulfoxides have often been separated completely or partially into the enantiomers. Various resolution techniques have been used, but the most important method has been via diastereomeric salt formation. Recently, resolution via complex formation between sulfoxides and homochiral compounds has been demonstrated and will likely prove of increasing importance as a method of separating enantiomers. Preparative liquid chromatography on chiral columns may also prove increasingly important it already is very useful on an analytical scale for the determination of enantiomeric purity. 

Imamoto and Koto131 prepared some interesting chiral oxidants (104) by the reaction of iodosyl benzene with tartaric anhydride. Methyl p-tolyl sulfide (105) was oxidized by 104c to the sulfoxide in 80% yield with 40% e.e. Methyl p-tolyl, o-tolyl and o-anisyl sulfides (105-107) were oxidized by 104a to their sulfoxides with the enantiomeric purities shown. 

Hydroxy-L-prolin is converted into a 2-methoxypyrrolidine. This can be used as a valuable chiral building block to prepare optically active 2-substituted pyrrolidines (2-allyl, 2-cyano, 2-phosphono) with different nucleophiles and employing TiQ as Lewis acid (Eq. 21) [286]. Using these latent A -acylimmonium cations (Eq. 22) [287] (Table 9, No. 31), 2-(pyrimidin-l-yl)-2-amino acids [288], and 5-fluorouracil derivatives [289] have been prepared. For the synthesis of p-lactams a 4-acetoxyazetidinone, prepared by non-Kolbe electrolysis of the corresponding 4-carboxy derivative (Eq. 23) [290], proved to be a valuable intermediate. 0-Benzoylated a-hydroxyacetic acids are decarboxylated in methanol to mixed acylals [291]. By reaction of the intermediate cation, with the carboxylic acid used as precursor, esters are obtained in acetonitrile (Eq. 24) [292] and surprisingly also in methanol as solvent (Table 9, No. 32). Hydroxy compounds are formed by decarboxylation in water or in dimethyl sulfoxide (Table 9, Nos. 34, 35). 

Enzyme-mediated chiral sulfoxidation has been reviewed comprehensively in historical context [188-191]. The biotransformation can be mediated by cytochrome P-450 and flavin-dependent MOs, peroxidases, and haloperoxidases. Owing to limited stability and troublesome protein isolation, a majority of biotransformations were reported using whole-cells or crude preparations. In particular, fungi have been identified as valuable sources of such biocatalysts and the catalytic entities have not been fully identified in all cases. 

Within the biooxidation of disulfides, chiral thiosulfinates become available. Tert-Butyl tert-butanethiosulfinate represents a particularly valuable chiral auxiliary for the preparation of several chiral sulfoxides and sulfinimines, which can be subsequently transformed into branched amine compounds, P-aminoacids, and chiral aziridines. This product is accessible readily by mediated biooxidation of tert-butyl... 

Sulfoxides without amino or carboxyl groups have also been resolved. Compound 3 was separated into enantiomers via salt formation between the phosphonic acid group and quinine . Separation of these diastereomeric salts was achieved by fractional crystallization from acetone. Upon passage through an acidic ion exchange column, each salt was converted to the free acid 3. Finally, the tetra-ammonium salt of each enantiomer of 3 was methylated with methyl iodide to give sulfoxide 4. The levorotatory enantiomer was shown to be completely optically pure by the use of chiral shift reagents and by comparison with a sample prepared by stereospecific synthesis (see Section II.B.l). The dextrorotatory enantiomer was found to be 70% optically pure. 

With this encouraging result from the model system, a gram quantity of the racemic sulfoxide 40 was prepared by oxidation of benzoxathiin 16 with mCPBA and a small amount of chiral sulfoxide (A)-40 with 94% ee was isolated by subsequent chiral HPLC separation (Scheme 5.12). When chiral sulfoxide (S)-40 was treated with borane-dimethylsulfide, a clean reduction of the olefin and the sulfoxide was observed. More surprisingly, only the desired cis-diaryl dihydrobenzoxathiin 12 was observed in high yield and unchanged 94% ee. No trans-isomer or 16 was observed. With this proof of concept in hand, an efficient... 

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