Asymmetric epoxidation defined

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]. 

Preparation. A number of methods have been reported for both the racemic and asymmetric preparations of l-amino-2,3-dihydro-lH-inden-2-ol (1), most commonly starting from inexpensive and readily available indene. These methods have been described in detail in recent reviews. The valuable properties of 1 as both a component of a medicinally active compound and as a chirality control element, derive primarily from its rigid and well-defined stereochemical structure. As a result, the compound is most desirable in enantiomerically pure form. One of the most efficient asymmetric syntheses of 1, which may be employed for the synthesis of either enantiomer of the target molecule, involves an asymmetric epoxidation (89% yield, 88% ee) of indene to give epoxide 2 using the well-established Jacobsen catalyst. This is followed by a Ritter reaction using oleum in acetonitrile resulting in conversion to the oxazoline (3) which is subsequently hydrolysed to the amino alcohol. Fractional crystallization with a homochiral diacid permits purification to >99% ee (eq 1). ... 

Summing up, a short review about the methods of enantioselective epoxidation with peroxidic reagents has been given. In the forefront of the discussion there was the titanium/tartrate-catalyzed asymmetric epoxidation discovered by Katsuki and Sharpless, which is characterized by simplicity, reliability, and high enantio-selectivity, but also by well-defined limits. Moreover, I have tried to include some results obtained in this field by our group adding them to the knowledge of asymmetric epoxidation. 

Miller and coworkers reported that well-defined peptide-based catalysts are able to induce asymmetric epoxidation of cyclic alkenes bearing amide or carbamate moieties close to the alkene (Scheme 5.11). The catalyst is based on transient generation of peptide-based peracids in a catalytic mode with turnover [40]. For the functional evaluation of catalyst 27, different analogs were prepared. First, the... 

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. 

One of the most potent frameworks for the synthesis of two contiguous stereochemically defined asymmetric centers is the chiral epoxy functionality. Prepared in molar-scale quantity from dimethyl L-tartrate (la), bromohydrin 860 is a shelf-storable solid that undergoes selective reduction at the a-hydroxy ester function with borane-dimethylsulfide complex in the presence of catalytic sodium borohydride to provide a 4 1 mixture of methyl (2S,3S)-2-bromo-3,4-dihydroxybutanoate (861) and methyl (2i, 3i )-3-bromo-2,4-dihydroxybutanoate (862). Without purification this mixture is treated with ert-butyldimethylsilylchloride and then exposed to sodium methoxide, which results in conversion to the single epoxide methyl (2i, 3iS)-4-( err-butyldimethylsilyloxy)-2,3-epoxybutanoate (863) in 95% yield and with 99% optical purity (Scheme 188). 

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