Chiral sulfimides

Uemura and co-workers (91) demonstrated that copper catalysts effectively transfer nitrenoid groups to sulfides generating chiral sulfimides. A complex obtained from CuOTf and 55d catalyzes nitrenoid transfer to prochiral sulfides to afford products such as 139 in moderate to poor enantioselectivities (<71% ee, Eq. 78). Nitrenoid transfer occurs selectively to the sulfur atom of allylic sulfides generating allylic sulfenamide (140) in moderate selectivity, after [2,3] sigmatropic rearrangement of the initial sulfimide 141, Eq. 79. 

The replacement of the oxygen atom in sulfoxides by nitrogen leads to a new class of chiral sulfur compounds, namely, sulfimides, which recently have attracted considerable attention in connection with the stereochemistry of sulfoxide-sulfimide-sulfoximide conversion reactions and with the steric course of nucleophilic substitution at sulfur. The first examples of chiral sulfimides, 88 and 89, were prepared and resolved into enantiomers by Phillips (127,128) by means of the brucine and cinchonidine salts as early as 1927. In the same way, Kresze and Wustrow (129) were able to separate the enantiomers of other structurally related sulfimides. 

The best and most versatile method for the synthesis of chiral sulfimides takes advantage of the stereospecific reaction of chiral... 

An alternative stereospecific synthesis of chiral sulfimides reported by Nudelman (137) consists of the reaction of the diastereomeric menthyl p-toluenesulfinimidoates 90 with Gri ard reagents giving the optically active sulfimide 91. This reaction, like the Andersen synthesis of chiral sulfoxides, proceeds with inversion of configura-... 

Two methods are described for the preparation of chiral amino-sulfonium salts. The first is based on the alkylation of nitrogen in chiral sulfimides. In this way the optically active aminosulfonium salt 123 was obtained from sulfimide 124, as shown in eq. [63] (164). 

Uemura and co-workers discovered that prochiral sulfides react with [N-(p-toluenesulfonyl)imino]phenyliodinane 207 in the presence of bis(oxazoline) ligands to form the corresponding chiral sulfimides. ° For example, ( )-cinnamyl phenyl sulfide 220 reacted with 207 in the presence of copper(I) triflate and ent-6 to form the chiral sulfimide 221 in 80% yield (58% ee) as shown in Figure 9.63. 

Electrophilic nitrogen compounds, such as arenesulfonyloxyamines, can convert alkenes to aziridines without the intervention of free nitrenes (80CC560). The ylide Ph2S+-NH adds stereospecifically to E and Z conjugated alkenes, and chiral sulfimides can transfer chirality to the aziridines formed (80T73). These reactions are often named aziridinations . 

Other ligands giving >90% ee for the alkylation or amination of 19 have been reported but will not be described in detail. They include derivatives of 3 [36], ferrocene-based ligands [54-57], l.l -binaphthyl-based ligands [58-60], natural product-based ligands such as fenchone [61], cholesterol [62], or carbohydrates [63,64], chiral aryl chromium complexes [65,66], chiral sulfimides [67], newP,N-ligands [19,22,52,53,68-78], and others [79-82]. 

The synthesis of sulfoximides and sulfimides has attracted considerable attention in recent years due to the potential utility of these compounds as efficient auxiliaries and chiral ligands in asymmetric synthesis (reviews [86-88]). Transition metal-catalyzed nitrene transfer to sulfoxides and sulfides is an efficient and straightforward way to synthesize sulfoximides and sulfimides, respectively. Bach and coworkers reported the first iron-catalyzed imination of sulfur compounds with FeCl2 as catalyst and B0CN3 as nitrene source. Various sulfoxides and sulfides were... 

In addition to sulfimides, the nitrogen analogs of sulfinates and sulfinamides are chiral and have been obtained as optically active compounds. For instance, the synthesis of diastereomeric menthyl p-toluenesulfinimidoates 90 mentioned above was effected by Cram and his collaborators (18,137) on two ways. The first comprised the reaction of racemic A -tosyl-p-tolueneiminosulfinyl chloride 92 with menthol, followed by separation of the diastereomers of 90, whereas in the second method the reaction of the ester (->45 with chloramine T was utilized. 

Recent studies on chiral sulfoximides, espcially in the laboratories of Cram, Johnson, Andersen, and Stirling, have been centered on the stereospecific interconversions between chiral sulfoxides, sulfimides, and sulfoximides, as well as on the construction of new stereochemical cycles. For the sake of brevity, only some selected results from these extensive studies are presented here to illustrate various stereospecific syntheses of chiral sulfoximides. 

Oae (251,252) as well as Darwish and Datta (253) investigated the process of thermal racemization of chiral alkylarylsulfimides and diarylsulfimides. It was found to proceed at temperatures as low as 65 to 100°C with a rate constant of the order 1 to 10 X 10" sec" , which corresponds to an activation energy of about 23 to 30 kcal/mol. These data indicate that the thermal racemization of sulfimides is much faster than that of analogous sulfoxide systems. The racemization of sulfimides is a unimolecular reaction practically independent of the polarity of the solvent this property, coupled with the absence of decomposition products, supports the view that racemization of sulfimides occurs by pyramidal inversion. 

The oxidative conversion of the (-)-(5 )-A-tosyl methyl-p-tolyl-sulfimide 91 to the corresponding (-)-(/ )-sulfoximide 151 is of considerable interest because the absolute configurations of the substrate and product were established by the quasi-racemate method and by X-ray analysis (98), respectively. Therefore, the stereochemical result of this experiment indicates unequivocally that oxidation of chiral tricoordinate sulfur compounds proceeds with retention of configuration. 

The cis- and frans-sulfoxides (551) and (552) have been O-methylated with Meerwein s reagent. Reaction of the methoxy derivative with MeMgBr proceeds with inversion of configuration (Scheme 211) (74JA8026). The stereochemical course of the interconversions of sulfoxide, sulfimide and sulfoximide in the 2,3-dihydrobenzo[6]thiophene series has been investigated (73JA1916). The reaction cycle (Scheme 212) involves both nucleophilic and electrophilic substitution at chiral sulfur. Inversion of configuration takes place in the conversion of (553) to (554) in pyridine. 

Armstrong et al. reported the amination of various sulfides with iV-acyloxaziridines <2002CC904, 2003TL5335>. Treatment of various sulfides 87 with 88 in trifluoroethanol afforded sulfimides 89 and sulfoxides 90, with the former predominating (Table 4). Asymmetric sulfimidation with a chiral oxaziridine 92 gave low diastereoselectivities (Equation 2) <2003TL5335>. 

Keywords Sulfoxides, Sulfones, Sulfimides, Sulfoximines, Chiral metal complexes... 

In summary, we have presented a variety of metal-based catalysts which are able to mediate the asymmetric oxidations of sulfides to the corresponding sulfoxides and sulfimides. Although very different approaches relying on distinct metal complexes are known, there is still a demand for an appropriate system which would allow the transformation of any sulfide to occur with high enantioselec-tivity. Especially the rational design of chiral complexes able to selectively oxidize substrates, in particular, those compounds other than aryl methyl sulfides is still a major challenge. 

Scheme 18.67 Preparation and rearrangement of chiral allylic sulfimides.—...

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