Allyl alcohols achiral, Sharpless epoxidation

The emergence of the powerful Sharpless asymmetric epoxida-tion (SAE) reaction in the 1980s has stimulated major advances in both academic and industrial organic synthesis.14 Through the action of an enantiomerically pure titanium/tartrate complex, a myriad of achiral and chiral allylic alcohols can be epoxidized with exceptional stereoselectivities (see Chapter 19 for a more detailed discussion). Interest in the SAE as a tool for industrial organic synthesis grew substantially after Sharpless et al. discovered that the asymmetric epoxidation process can be conducted with catalytic amounts of the enantiomerically pure titanium/tartrate complex simply by adding molecular sieves to the epoxidation reaction mix-... 

In a continuation of his studies on asymmetric P-lactam synthesis, Evans [42] utilized a,P-epoxyaldehydes 49a and 49b, prepared in two steps from achiral allylic alcohols via Sharpless asymmetric epoxidation and Swern oxidation, as chiral glyoxal synthons for the ketene-imine cycloaddition. Diastereosel-ection was excellent, ranging from 90 10 to 97 3 with overall yield of 50 up to 84% (for Schiff base formation and cycloaddition) after recrystallization or chromatographic purification of the major diastereomer. The sense of asymmetric induction correlated with that obtained in the analogous glyceraldehyde reaction, as established by periodic acid cleavage to aldehydes 51. 

Fig. 3.35. Enantioselective Sharpless epoxidation of achiral primary allylic alcohols.

Fig. 3.37. Mechanistic details of Sharpless epoxidations, part II preferred transition state of enantioselective epoxidations of achiral primary allylic alcohols in the presence of l-(+)-DET (top) or d-(-)-DET (bottom).

Fig. 3.29. Enantioselective Sharpless epoxidation of achiral primary allyl alcohols. If the substrates are drawn as shown, the direction of the attack of the complexes derived for l-( + ) and d-(-)-DET can be remembered with the following mnemonic L, from lower face ...

The 2001 Nobel Prize in Chemistry was awarded to three organic chemists who have developed methods for catalytic asymmetric syntheses. An asymmetric (or enantioselective) synthesis is one that converts an achiral starting material into mostly one enantiomer of a chiral product. K. Barry Sharpless (The Scripps Research Institute) developed an asymmetric epoxidation of allylic alcohols that gives excellent chemical yields and greater than 90% enantiomeric excess. 

Sharpless asymmetric epoxidation ° is an enantioselective epoxidation of an allylic alcohol with ferf-butyl hydroperoxide (f-BuOOH), titanium tetraisopropoxide [Ti(0-fPr)4] and (-b)- or (—)-diethyl tartrate [(-b)- or (—)-DET] to produce optically active epoxide from achiral allylic alcohol. The reaction is diastereoselective for a-substituted allylic alcohols. Formation of chiral epoxides is an important step in the synthesis of natural products because epoxides can be easily converted into diols and ethers. 

Epoxides are key chiral synthetic intermediates and their enantioselective preparation by oxidation of achiral alkenes is a key reaction in many synthetic strategies. Sharpless asymmetric epoxidation is suitable for most allylic alcohols [26, 27], but few general procedures exist for unfunctionalized olefins. Jacobsen s manganese salen-mediated epoxidation is suitable for and gives good selectivities with Z-olefins (85 to 90% ee) [28]. The enzyme chloroperoxidase... 

Imido and 0x0 compounds are intermediates in many of the transfers of oxygen atoms and nitrene units to olefins to form epoxides and aziridines, and they are intermediates in many of the insertions of oxygen atoms and nitrene units into the C-H bonds of hydrocarbons to form alcohols and amine derivatives. The enantioselective epoxidation of allylic alcohols (Scheme 13.22) " is the most widely used epoxida-tion process, and the discovery and development of this process was one of the sets of chemistry that led K. Barry Sharpless to receive the Nobel Prize in Chemistry in 2001. The mechanism of this process is not well established, despite the long time since its discovery and development. Nevertheless, most people accept that transfer of the oxygen atom occurs from a titanium-peroxo complex - rather than from an 0x0 complex. Jacobsen s and Katsuki s - manganese-salen catalysts for the enantioselective epoxidations of unfunctionalized olefins, which were based on Kochi s achiral chromium- and manganese-salen complexes, are a second set of... 

Chemistry-based kinetic resolution methods, which make use of the preferential reaction of one enantiomer with a chiral reagent (e.g. hydroboration of racemic alkenes with diisopinocampheylborane) or an achiral reagent in the presence of an appropriate chiral catalyst (e.g. Sharpless epoxidation of racemic allylic alcohols with t-BuOOH in the presence of (2R,3R)- or (25,35)-diisopropyl tartrate and Ti(Oi-Pr)4) have not been exploited so far for the isolation of e.p. labeled substances. In contrast, biochemical methods have been widely used, particularly for the resolution of racemic a-[ " C]amino acids and various [ C]carboxylic acids. Such methods, including ... 

Initial attempts to convert the 2,3-tra J-2,6-tran5-tetrahydropyran aldehyde 2.197a to the epoxide 2.198 through asymmetric allylation and subsequent epoxidation were made (Scheme 2.41). Towards this end, aldehyde 2.198 was transformed to the homoaUyl alcohol 2.201 via Brown asymmetric allylation [95], was in turn exposed to a variety of epoxidation conditions, including Sharpless asymmetric epoxidation [146] as well as achiral reagents such as VO(acac)2/t-BuOOH [147, 148] and m-CPBA. Unfortunately, aU attempts were not effective for the installation of the epoxide. Instead, the former two reactions yielded three side products which were the results of the oxidation of the 1,3-dithiane moiety under oxidation reaction conditions. The latter resulted in the epoxide, but the poor diastereoselectivity (dr = 1 1) as well as significant loss of the PMB group were observed. 

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