Chiral sulfoxides processes

A chiral sulfoxide can be used as a leaving group for the asymmetric induction via addition-elimination process. 6-Lactam enolates are converted into the corresponding nitroalkenes substituted with lactams (Eq. 4.101).127... 

OpticaUy active iV-tosylsulfoximides produced in the copper-catalyzed reaction of chiral sulfoxides with tosyl azide may be hydrolyzed with strong acid (H2SO4) to optically active free sulfoximides. However, this procedure often fails and/or results in decomposition. It is interesting to note in this connection that a simple one-step method for the preparation of optically active unsubstituted sulfoximides has been reported recently by Johnson and co-workers (180). It involves the reaction between optically active sulfoxides and 0-mesi-tylsulfonylhydroxylamine and results in sulfoximides 60 of high optical purity. As expected, this imidation process occurs with retention of configuration at sulfur. 

Biooxidation of chiral sulfides was initially investigated in the 1960s, especially through the pioneering work of Henbest et al. [101]. Since then, many developments have been reported and are summarized in reviews [102,103], It would be helpful to reveal some structural or mechanistic details of enzymes involved in theoxidation processes. Biotransformations are also of great current interest for the preparation of chiral sulfoxides, which are useful as synthetic intermediates and chiral auxiliaries. Because extensive review of these transformations is beyond the scope of this chapter, only highlights are discussed in comparison with the abiotic enantioselective oxidations described earlier. Biooxidations by microorganisms and by isolated enzymes are discussed in Sections 6C.12.1. and 6C.12.2. 

Asymmetric Pummerer rearrangement is a very attractive reaction as previously described. In particular, the reactions induced by SKA work well, and may be synthetically exploited in many cases. The results described here demonstrate that the stereoselective a-deprotonation of the sulfoxide is a prerequisite process for asymmetric induction in the Pummerer reaction. Since many kinds of synthetic and enzymatic preparative methods of optically pure sulfoxides have been developed, the present Pummerer-type reaction will be applicable to many other chiral sulfoxides with one a-substituent, chiral vinylsulfoxides and chiral co-carbamoylsulfox-ides, thus leading to enantioselective syntheses of many new bioactive compounds in the near future. 

Induction in the chirality transfer from C-l to C-3 overrides that of the chirality transfer from the sulfur atom to C-3. Therefore, the chirality at the heteroatom only has an impact on systems lacking a stereogenic center at C-l. The two diastereomeric transition states for the rearrangement of such chiral sulfoxides are designated as exo and endo"1. These lead to the different enantiomers of the allylic alcohol. Their energy difference, which depends mainly on the substitution of the double bond, determines the enantioselectivity of the process. 

There are several efficient methods available for the synthesis of homochiral sulfoxides [3], such as asymmetric oxidation, optical resolution (chemical or bio-catalytic) and nucleophilic substitution on chiral sulfinates (the Andersen synthesis). The asymmetric oxidation process, in particular, has received much attention recently. The first practical example of asymmetric oxidation based on a modified Sharpless epoxidation reagent was first reported by Kagan [4] and Modena [5] independently. With further improvement on the oxidant and the chiral ligand, chiral sulfoxides of >95% ee can be routinely prepared by these asymmetric oxidation methods. Nonetheless, of these methods, the Andersen synthesis [6] is still one of the most widely used and reliable synthetic route to homochiral sulfoxides. Clean inversion takes place at the stereogenic sulfur center of the sulfinate in the Andersen synthesis. Therefore, the key advantage of the Andersen approach is that the absolute configuration of the resulting sulfoxide is well defined provided the absolute stereochemistry of the sulfinate is known. 

From their QSERR they find solute lipophilicity and steric properties as being responsible for analyte retention (k ) while enantioseparation (a) varied mainly with electronic and steric properties. The main difference between the analytes is that the enantioseparation of the esters is correlated with steric parameters that scale linearly with log a while the sulfoxides scale nonlinearly (parabolic), but this may be due to a computational artifact. The 3D-QSERR derived from field analysis revealed that while superpositioning of field maps for both analytes are not exactly the same, a similar balance of physicochemical forces involved in the chiral recognition process are at play for both sets of analyes. This type of atomistic molecular modeling, then, is a powerful adjunct to the type of modeling described earlier in this chapter and will, no doubt, be used more frequently in future studies. 

Another approach involves the stereoselective creation of the sulfinyl moiety by oxidative processes. One possibility is the use of a sulfide (4) bound to a chiral auxiliary R, with a structure or a functional group (usually a hydroxy) able to control the course of the transformation of sulfide (4) into sulfoxide (2). A second approach is the enantioselective oxidation of an achiral sulfide. In this case, the chiral auxiliary is connected to the oxidant, and the process is stoichiometric with respect to the chiral auxiliary. The most efficient production of chiral sulfoxides results where the chiral auxiliary is part of m oxidation catalyst, when, in principle, a large amount of enantiopure sulfoxide (2) is produced from a small amount of the chiral auxiliary. 

Sulfide Oxidation (Merck). A process for a chiral sulfoxide intermediate was developed using Kagan s Ti/tartrate and applied on a multikilogram scale for... 

A non-caibohydrate process has beat developed from the chiral sulfoxide 32 to produce the fluorinated dideoxynojirimycin derivative 33. ... 

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. 

The enzymatic oxygenation process is of particular value as there is a significant difference in the formation rates of sulfoxides and sulfones. The initial conversion of sulfide to the optically active sulfoxide by an MO is usually very fast compared to the subsequent oxidation step to sulfone, upon which chirality is lost (Scheme 9.26). In many cases, over-oxidation to sulfone is not observed at all when employing MOs. 

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