Ketones asymmetric olefin epoxidation

Chiral Ketone and Iminium Catalysts for Olefin Epoxidation Table 3 Asymmetric epoxidation with ketone 26... 

Dimethyl (2/ ,3 )-tartrate provides the central C4 building block. Homer olefination is used to attach the C2 building block at one end. Asymmetric Sharpless epoxidation converts the resulting olefin to the Cg epoxide. The Cn chain, produced from the Cg and C3 building blocks, is attached at the other end. The missing Ci atom is provided by CH2N2 an Arndt-Eistert reaction leads, via the Cxg diazo ketone, to the Cjg hydroxycarboxylic acid. Cycliza-tion of the seco-isomer gives enf-100 Scheme 52). 

Although ketone 62 is an effective epoxidation catalyst for a variety of trans- and trisubstituted olefins, epoxidation of cis- and terminal olefins using this ketone led to rather poor enantioselectivity." " To improve the performance of asymmetric epoxidation of other types of olefins, a new class of chiral oxazolidinone ketone catalysts was explored (Scheme 35.17)." ° High enantioselectivity was obtained for asymmetric epoxidation of cis- and terminal olefins with ketones 65" and 66, respectively. 

The past thirty years have witnessed great advances in the selective synthesis of epoxides, and numerous regio-, chemo-, enantio-, and diastereoselective methods have been developed. Discovered in 1980, the Katsuki-Sharpless catalytic asymmetric epoxidation of allylic alcohols, in which a catalyst for the first time demonstrated both high selectivity and substrate promiscuity, was the first practical entry into the world of chiral 2,3-epoxy alcohols [10, 11]. Asymmetric catalysis of the epoxidation of unfunctionalized olefins through the use of Jacobsen s chiral [(sale-i i) Mi iln] [12] or Shi s chiral ketones [13] as oxidants is also well established. Catalytic asymmetric epoxidations have been comprehensively reviewed [14, 15]. 

The oxidation of enol ethers and their derivatives is a useful method for the synthesis of a-hydroxy-ketones or their derivatives, which are versatile building blocks for organic synthesis. Since enol ethers and esters are types of olefin, some asymmetric epoxidation and dihydroxylation reactions have been applied to their oxidation. 

In studies of the asymmetric epoxidation of olefins, chiral peroxycarboxylic acid induced epoxidation seldom gives enantiomeric excess over 20%.1 Presumably, this is due to the fact that the controlling stereocenters in peroxycarboxylic acids are too remote from the reaction site. An enantiomeric excess of over 90% has been reported for the poly-(Y)-alanine-catalyzcd epoxidation of chalcone.2 The most successful nonmetallic reagents for asymmetric epoxidation have been the chiral TV-sulfonyloxaziridincs3 until asymmetric epoxidation reactions mediated by chiral ketones were reported. Today, the... 

Subsequently, high chemoselectivity and enantioselectivity have been observed in the asymmetric epoxidation of a variety of conjugated enynes using fructose-derived chiral ketone as the catalyst and Oxone as the oxidant. Reported enantioselectivities range from 89% to 97%, and epoxidation occurs chemoselectively at the olefins. In contrast to certain isolated trisubstituted olefins, high enantioselectivity for trisubstituted enynes is noticeable. This may indicate that the alkyne group is beneficial for these substrates due to both electronic and steric effects. 

Following their success with chiral ketone-mediated asymmetric epoxidation of unfunctionalized olefins, Zhu et al.113 further extended this chemistry to prochiral enol silyl ethers or prochiral enol esters. As the resultant compounds can easily be converted to the corresponding a-hydroxyl ketones, this method may also be regarded as a kind of a-hydroxylation method for carbonyl substrates. Thus, as shown in Scheme 4-58, the asymmetric epoxidation of enol silyl... 

Abstract Organo-catalyzed asymmetric epoxidation has received much attention in the past 30 years and significant progress has been made for various types of olefins. This review will cover the advancement made in the field of chiral ketone and chiral iminium salt-catalyzed epoxidations. 

Asymmetric epoxidation of olefins is an effective approach for the synthesis of enan-tiomerically enriched epoxides. A variety of efficient methods have been developed [1, 2], including Sharpless epoxidation of allylic alcohols [3, 4], metal-catalyzed epoxidation of unfunctionalized olefins [5-10], and nucleophilic epoxidation of electron-deficient olefins [11-14], Dioxiranes and oxazirdinium salts have been proven to be effective oxidation reagents [15-21], Chiral dioxiranes [22-28] and oxaziridinium salts [19] generated in situ with Oxone from ketones and iminium salts, respectively, have been extensively investigated in numerous laboratories and have been shown to be useful toward the asymmetric epoxidation of alkenes. In these epoxidation reactions, only a catalytic amount of ketone or iminium salt is required since they are regenerated upon epoxidation of alkenes (Scheme 1). 

In 1984, Curci and coworkers reported asymmetric epoxidation of olefins with ketones... 

A catalytic amount of ketone 26 was used to investigate the substrate scope of the asymmetric epoxidation. High enantioselectivities can be obtained for a wide variety of trans- and trisubstituted olefins (Table 3, entries 1 ) [54]. Simple trans-olefins, such as franx-7-tetradecene, can be epoxidized in high yield and enantiomeric excess, indicating that this asymmetric epoxidation is generally suitable for frani-olefms. 2,2-Disubstituted vinyl silanes are epoxidized in high ees (Table 3, entries 5, 6) and enantiomerically enriched 1,1-disubstituted epoxides can be... 

In addition to the enantioselective epoxidation of trans- and trisnbstitnted olefins, efforts have also been made for the asymmetric epoxidation of cis- and terminal olefins. Glncose-derived ketone 55 was reported to be a highly enantioselective catalyst for the epoxidation of varions cw-olefins and certain terminal olefins (Fig. 11, Table 4) [97-100]. The resnlts of epoxidation with ketone 55 indicate that a n... 

Previously, some fluorocyclohexanones were used in a catalytic amount with Oxone for asymmetric epoxidation reaction, but they gave a poor ee . It was found later that chiral ketones derived from fructose work well as asymmetric epoxidation catalysts and show high enantioselectivity in reactions of /rani-disubstituted and trisubsti-tuted olefins ". Cis and terminal olefins show low ee under these reaction conditions. Interestingly, the catalytic efficiency was enhanced dramatically upon raising the pH. Another asymmetric epoxidation was also reported using Oxone with keto bile acids. ... 

AN OXAZOLIDINONE KETONE CATALYST FOR THE ASYMMETRIC EPOXIDATION OF cis-OLEFINS... 

REGIO- AND STEREO-CONTROLLED OXIDATIONS AND REDUCTIONS Table 6.7 Asymmetric epoxidation of olefins by ketone 2. 

Chiral dioxirane that was also generated in situ from the corresponding ketone and Oxone was first used for catalytic asymmetric epoxidation by Curd et al., although enantioselectivity was low [7], Later, Yang et al. disclosed that this approach had a bright prospect if used with a combination of Oxone and chiral ketone 3 [8]. Ketone 3 is converted into the corresponding dioxirane in situ, which epoxidizes olefins (Scheme 6B.5). 

The catalytic asymmetric epoxidation of electron-deficient olefins, particularly a,P-unsaturated ketones, has been the subject of numerous investigations, and as a result a number of useful methodologies have been elaborated [44], Among these, the method utilizing chiral phase-transfer catalysis occupies a unique position in terms of its practical advantages. Moreover, it also allows the highly enantioselective epoxidation of trans-a,P-unsaturated ketones, particularly chalcone. 

It should be noted that the related imine-oxaziridine couple E-F finds application in asymmetric sulfoxidation, which is discussed in Section 10.3. Similarly, chiral oxoammonium ions G enable catalytic stereoselective oxidation of alcohols and thus, e.g., kinetic resolution of racemates. Processes of this type are discussed in Section 10.4. Whereas perhydrates, e.g. of fluorinated ketones, have several applications in oxidation catalysis [5], e.g. for the preparation of epoxides from olefins, it seems that no application of chiral perhydrates in asymmetric synthesis has yet been found. Metal-free oxidation catalysis - achiral or chiral - has, nevertheless, become a very potent method in organic synthesis, and the field is developing rapidly [6]. 

The idea of using chiral ketones as catalysts for asymmetric epoxidation of olefins was first addressed by Curci et al. in the middle of the 1980s [7]. In this initial ex-... 

Fluoro ketones based on the tropinone skeleton and other bicyclo[3.2.1]octan-3-ones were studied by Denmark et al. (eg. 23) [34, 35] and Armstrong et al. (eg. 24) [36, 37]. Ketone 24 proved particularly efficient for asymmetric epoxidation of unfunctionalized olefins (Table 10.3). 

In the course of their exploration of structure-activity relationships for ketone catalysts, Denmark et al. noted that oxoammonium salts such as 29-33 are very efficient catalysts of the epoxidation of olefins [34a]. Unfortunately, enantiomeric excesses achieved with this class of ketone catalyst have not yet exceeded 40% (30, epoxidation of tram-fl-rn eth yI styrene . With the fhiorinated oxoammonium catalyst 23 already mentioned, however, 58% ee was achieved in the asymmetric epoxidation of trans-stilbene [34b]. 

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