Epoxidation asymmetric methods

Alternatively, epoxides can be formed with concomitant formation of a C-C bond. Reactions between aldehydes and various carbon nucleophiles are an efficient route to epoxides, although the cis. trans selectivity can be problematic (see Section 9.1.4). Kinetic resolution (see Section 9.1.5.2) or dihydroxylation with sequential ring-closure to epoxides (see Section 9.1.1.3) can be employed when asymmetric epoxidation methods are unsatisfactory. 

Asymmetric epoxidation, dihydroxylation, aminohydroxylation, and aziridination reactions have been reviewed.62 The use of the Sharpless asymmetric epoxidation method for the desymmetrization of mesa compounds has been reviewed.63 The conformational flexibility of nine-membered ring allylic alcohols results in transepoxide stereochemistry from syn epoxidation using VO(acac)2-hydroperoxide systems in which the hydroxyl group still controls the facial stereoselectivity.64 The stereoselectivity of side-chain epoxidation of a series of 22-hydroxy-A23-sterols with C(19) side-chains incorporating allylic alcohols has been investigated, using m-CPBA or /-BuOOH in the presence of VO(acac)2 or Mo(CO)6-65 The erythro-threo distributions of the products were determined and the effect of substituents on the three positions of the double bond (gem to the OH or cis or trans at the remote carbon) partially rationalized by molecular modelling. 

Asymmetric oxidations have followed the usual development pathway where face selectivity was observed through the use of chiral auxiliaries and templates. The breakthrough came with the Sharpless asymmetric epoxidation method, which, although stoichiometric, allowed for a wide range of substrates and the stereochemistry of the product to be controlled in a predictable manner.4... 

Tu Y, Wang ZX, Shi Y (1996) An efficient asymmetric epoxidation method for irans-olefins mediated by a fructose-derived ketone. J Am Chem Soc 118 9806... 

One of the most important advances in the past decade has been the development of asymmetric epoxidation methods for unfunctionalized alkenes using dioxiranes generated from chiral ketone precursors (Scheme 23) <1995TL5831, 1997JOC8964>. 

Tu, Y., Wang, Z.-X., Shi, Y. An Efficient Asymmetric Epoxidation Method fortrans-Olefins Mediated by a Fructose-Derived Ketone. J. Am. Chem. Soc. 1996,118, 9806-9807. 

Asymmetric oxidations have followed the usual development pathway in which face selectivity was observed through the use of chiral auxiliaries and templates. The breakthrough came with the Sharpless asymmetric epoxidation method, which, although stoichiometric, allowed for a wide range of substrates and the stereochemistry of the product to be controlled in a predictable manner [1]. The need for a catalytic reaction was very apparent, but this was developed and now the Sharpless epoxidation is a viable process al scale, although subject to the usual economic problems of a cost-effective route to the substrate (see later) [2]. The Sharpless epoxidation has now been joined by other methods and a wide range of products are now available. The pow er of these oxidations is augmented by the synthetic utility of the resultant epoxides or diols that can be used for further transformations, especially those that use a substitution reaction (see Chapter 7) [1]. 

The Sharpless asymmetric epoxidation method has been used with great success for the synthesis of 2,6-dideoxyhexoses and an enormous range of alditols. Unfortunately, it is not possible to do full justice to this work in this review however, it is worth noting that after the Ti -mediated asymmetric epoxidation the products can be reduced in a highly stereoselective fashion using sodium bis(methoxyetho7Qr)aluminium hydride (Red-al). ... 

Examples of Pharmaceutical Product Synthesis In this section, a couple of examples concerning the application of the Mn(salen) asymmetric epoxidation method are described, focusing on cis substituted alkenes as intermediate substrates that are selectively oxidized by this catalytic system. Other examples of application of Mn(salen) on different classes of alkenes for the synthesis of drugs are reported in a recent review paper. ... 

Synthesis of Indinavir An example of the application of the Jacobsen asymmetric epoxidation method is the large... 

Despite the tremendous success of hydroxyl-directed asymmetric epoxidation of allylic alcohols and homoallylic alcohols, the development of efficient asymmetric epoxidation methods for unfunctionalized olefins is still of great importance. In the mid-1980s, Kochi and co-workers studied achiral epoxidation of unfunctionalized olefins using achiral Cr(III)-salen and Mn(lll)-salen comlexes as catalysts, and they proposed that a high valent metal oxo (such as 0=Cr(V)-salen and 0=Mn(V)-salen species) as the reactive intermediate was responsible for the epoxidation of olefins. Such a reactive intermediate was formed in a catalytic cycle by oxidation of the catalyst (such as Cr(III)-salen or Mn(lll)-salen complex) with the stoichiometric oxidant (such as PhlO or NaOCl). ... 

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