Enantiomeric sulfoximine

Asymmetric induction by sulfoxide is a very attractive feature. Enantiomerically pure cyclic a-sulfonimidoyl carbanions have been prepared (98S919) through base-catalyzed cyclization of the corresponding tosyloxyalkylsulfoximine 87 to 88 followed by deprotonation with BuLi. The alkylation with Mel or BuBr affords the diastereomerically pure sulfoximine 89, showing that the attack of the electrophile at the anionic C-atom occurs, preferentially, from the side of the sulfoximine O-atom independently from the substituent at Ca-carbon. The reaction of cuprates 90 with cyclic a,p-unsaturated ketones 91 was studied but very low asymmetric induction was observed in 92. 

Recently, enantiomerically pure vinylic sulfoximines have been shown to undergo effective and highly stereocontrolled conjugate addition of hydrocarbon groups using organocopper reagents108. 

Two types of sulfoximinocarboxylates (analogous to sulfinylcarboxylates 16), namely 5 -aryl-5 -methoxycarbonylmethyl-A(-methyl sulfoximine 36 and -methyl-5 -phenyl-A(-ethoxycarbonyl sulfoximine 37, were subjected to hydrolysis in the presence of PLE in a phosphate buffer. As a result of a kinetic resolution, both the enantiomerically enriched recovered substrates and the products of hydrolysis and subsequent decarboxylation 38 and 39, respectively, were obtained with moderate to good ees (Equations 20 and 21). Interestingly, in each case the enantiomers of the substrates, having opposite spatial arrangement of the analogous substituents, were preferentially hydrolysed. This was explained in terms of the Jones PLE active site model. ... 

The Harmata group has also developed a route to enantiomerically pure 2,1-benzothiazines. The process involves the /V-arylation of sulfoximines using the Buchwald-Hartwig reaction conditions, <02MI3 99JOM(576)125> a reaction first reported by Bolm... 

The Harmata group s initial report concerned a one-pot, one-operation procedure <99AG(E)2419> for the synthesis of enantiomerically pure 2,1-benzothiazines via the Buchwald-Hartwig reaction reported by Bolm <98TL5731 OOJOC169> for sulfoximine N-arylation. For example, treatment of ortho-bromobenzaldehyde 78 with enantiomerically pure N-H sulfoximine 77a in the presence of a palladium catalyst and base afforded the benzothiazine 79 in 78% yield (Scheme 22). Both C-N bond formation and condensation occurred during the reaction, a phenomenon that appears general for aldehydes like 78. 

Reggelin et al. reported the application of methylated, enantiomerically pure acyclic and cyclic 2-alkenyl sulfoximines 203 for the synthesis of highly substituted aza(poly)cyclic ring systems 204 under complete stereocontrol <06JA4023 06S2224>. 

Endocyclic allylic sulfoximines 5 were synthesized from cydoalkanones and lithi-ated enantiomerically pure (S)-S-methyl-S-phenylsulfoximine, by addition and subsequent elimination and isomerization of the intermediate vinylic sulfoximines. 

Synthesis of the polymer-bound allyl sulfoximine 60 was accomplished by the addition-elimination-isomerization route starting from the enantiomerically pure polymer-bound N-methyl-S-phenylsulfoximine 59, which was prepared as previously described from Merrifield resin and sulfoximine 12 with a loading of 84% (Scheme 1.3.23) [42]. The successive treatment of resin 59 with n-BuLi in THF and with isovaleraldehyde furnished the corresponding polymer-bound lithium alcoholate, which upon reaction with ClC02Me and DBU afforded the corresponding polymer-bound vinylic sulfoximine (not shown in Scheme 1.3.23), the isomerization of which with DBU in MeCN afforded sulfoximine 60. 

The reaction proceeds stereospecifically, giving sulfoximines from the corresponding enantiomerically enriched sulfoxides without racemization. The NH-sulfoxi-mines can then be obtained after Boc cleavage with trifluoroacetic acid. Bolm et al. applied this reaction in the synthesis of sulfoximines having a benchrotene skeleton (Scheme 3.55) [171]. 

P-Hydroxy sulfoximines are thermally labile and revert to their starting carbonyl compound and sulfoximine on mild thermolysis. This property has been exploited effectively as a method for the resolution of racemic chiral cyclic ketones.65 For example, the addition of the lithium salt of (+)-(S)-2b (99% ee) under kinetically controlled conditions (-78 °C) to racemic menthone gave three of the four possible diastereomeric adducts. The major two adducts resulted from attack on the menthone from the equatorial direction. These diastereomeric adducts could be readily separated by column chromatography. Thermolysis of the individual two major diastereomeric carbinols at 140 °C gave d- and /-menthone, respectively, in high enantiomeric purities (90-93% ee). This methodology has been successfully applied to the resolution of other 2-substituted cyclohexanones as well as other chiral ketones that have served as advanced synthetic intermediates for the synthesis of natural products.66-69... 

Reductive elimination of (3-hydroxy sulfoximines with aluminum amalgam in acetic acid gives alkenes in good yields.70In one study, the resolved carbinol adducts of the ketone 93 and (+)-(S)-2b were individually treated with aluminum amalgam in acetic acid to give natural (-)-(3-panasinsene and its antipode in high enantiomeric purity.71... 

Resolved P-hydroxy sulfoximines derived from cyclic enones undergo dias-tereoselective Simmons-Smith cyclopropanation reactions to give, after thermolysis, cyclopropylketones in high enantiomeric purity (94-98%). Cyclopropanation occurs syn to the hydroxyl group of the P-hydroxy sulfoximine. This method is less diastereoselective for acyclic enones.73... 

Osmylation of diastereomerically pure P-hydroxy sulfoximines, derived from 2a and cyclic enones, with a catalytic amount of osmium tetroxide (5 mol%) and trimethylamine V-oxide (1.5 equiv) gives diastereomerically pure triols which on thermolysis yield 2,3-dihydroxy cyclic ketones in high enantiomeric purity ( 100% ee). Osmylation occurs syn to the sulfoximine group.74... 

Treatment of enantiomerically pure cyclic sulfonimidates 6 and 7 with allyllithium or allylmagnesium bromide gives optically active allylic sulfoximines 8 and 9 (R = allyl) as described in Section II.A.13 The reactions of /V-phenyl-S-(methyl-phenyl)sulfoximidoyl chloride 109 with allyltrimethylsilane or allyltributylstan-... 

Enantiomerically pure (fs)-acyclic sulfoximines 203 react with n-BuCuLil in the presence of boron trifluoride to give almost exclusively y-substitution products... 

Further experiments, in which the stereochemical outcomes could be rationalized as arising from analogous coordinated intermediates to 226 and 227, were performed on the enantiomerically pure vinyl sulfoximines 228 and 231.12 Vinyl sulfoximine 228 underwent conjugate addition of R2CuLi in the expected stereochemical sense, presumably via a coordinated intermediate analogous to 226 (Table... 

The reaction of racemic A-phthalimido-S-p-tolyl-S-vinylsulfoximine with a deficiency (0.5 molar equiv) of enantiomerically pure (-)-ephedrine resulted in a kinetic resolution of the vinyl sulfoximine.113 When the reaction was conducted at -30 °C the unreacted vinyl sulfoximine could be recovered with an enantiomeric purity of 46%. (-)-Amphetamine and (+)-l-phenylethylamine were not effective for kinetic resolution. The analogous (Z)-propenyl sulfoximine also underwent kinetic resolution with (-)-ephedrine, but the extent of kinetic resolution was not determined. 

In 1979, Johnson reported the enantioselective reduction of ketones with stoichiometric amounts of optically active (1-hydroxy sulfoximine-borane complexes.131 Prochiral alkyl phenyl ketones (RCOPh) undergo enantioselective reduction with enantiomerically pure p-hydroxy sulfoximine borane complexes (301 and 302). These complexes are prepared by reaction of the corresponding P-hydroxy sulfoximine with borane at -78 °C. The structures 301 and 302 have been suggested for these complexes. In the case of the borane complex 301, the enantioselectivity increased as the steric bulk of the R substituent of the ketone (RCOPh) was decreased from IV to Me. The analogous reductions of methyl alkyl ketones (MeCOR) with these borane complexes were less enantioselective (3-27% ee).131... 

In 1993, Bolm reported that these reactions could be performed using catalytic quantities (10 mol%) of the chiral P-hydroxy sulfoximine.132 The enantiomeric purities of the product alcohols ranged from 52% (1-indanone) to 93% (PhCOCHjOSiRj). In many cases the enantiomeric purities were enhanced using sodium borohydride as reductant in the presence of chlorotrimethylsilane.133 These methods have been extended to the asymmetric reductions of imines.134 /V-SPh-substituted imines gave the highest enantioselectivities and these reductions proceeded in the same stereochemical sense as the reductions of ketones. 

Optically active P-hydroxy /V-methyl sulfoximines have been used as catalysts for the enantioselective transfer of an ethyl group from diethylzinc to aldehydes to give secondary alcohols in enantiomeric excesses of 61-88%.127,135 Related chiral ligands have been used with nickel acetylacetone to promote the enantioselective Michael addition of diethylzinc to chalcones.136... 

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