Epoxidations ketone-mediated

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... 

Mechanistic studies103 revealed that chiral ketone-mediated asymmetric epoxidation of hydroxyl alkenes is highly pH dependent. Lower enantioselectivity is obtained at lower pH values at high pH, epoxidation mediated by chiral ketone out-competes the racemic epoxidation, leading to higher enantioselectivity. (For another mechanistic study on ketone-mediated epoxidation of C=C bonds, see Miaskiewicz and Smith.104)... 

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... 

Sello et al. have reviewed recent developments in oxirane preparation including metal- and ketone-mediated methods, the synthesis of epoxides from carbonyls, and enzymatic reactions <2006CSY457>. 

In the realm of epoxidations without the use of transition metals, dioxirane-mediated processes are among the most versatile. While the use of stoichiometric amounts of even the simplest dioxiranes can still be experimentally cumbersome, novel catalytic systems eontinue to emerge. For example, the PEG-immobilized trifluoroacetophenone 17 is a convenient dioxirane precursor that is highly active, soluble in both water and organic solvents, and easily recoverable and reusable. In the presence of Oxone, this ketone mediates the efficient epoxidation of sensitive substrates, such as the BOC-protected aminostyrene 18 04TL6357>. 

Proceeding via a similar reaction mechanism to the ketone-mediated epoxidation reactions, iminium salts offer an alternative source of catalysts for asymmetric organocatalytic epoxidations. The first example of the appHcation of iminium salts to asymmetric epoxidations used dihydroisoquinolinium-based catalyst 20 (Figure 19.9), affording a 33% ee for the epoxidation of ( )-stilbene [81]. 

Discovering highly enantioselective ketone catalysts for asymmetric epoxidation has proven to be a challenging process. As shown in Scheme 3.62, quite a few processes are competing with the catalytic cycle of the ketone mediated epoxidation, including racemization of chiral control elements, excessive hydration of the carbonyl, facile... 

Until this work, the reactions between the benzyl sulfonium ylide and ketones to give trisubstituted epoxides had not previously been used in asymmetric sulfur ylide-mediated epoxidation. It was found that good selectivities were obtained with cyclic ketones (Entry 6), but lower diastereo- and enantioselectivities resulted with acyclic ketones (Entries 7 and 8), which still remain challenging substrates for sulfur ylide-mediated epoxidation. In addition they showed that aryl-vinyl epoxides could also be synthesized with the aid of a,P-unsaturated sulfonium salts lOa-b (Scheme 1.4). 

Epoxy Esters, Amides, Acids, Ketones, and Sulfbnes 1.2.3.1 Sulfur Ylide-mediated Epoxidation... 

The electron-rich thiophene ring system can be elaborated into complex, fused thiophenes by acid-mediated intramolecular annelation reactions. For example, treatment of alcohol 96 with trimethylsilyl triflate promoted a Friedel-Crafts acylation and subsequent dehydration giving benzo[b]thiophene 97, a potential analgesic <00JMC765>. Treatment of ketone 98 with p-toluenesulfonic acid resulted in the formation of fused benzo[b]thiophene 99 <00T8153>. Another variant involved the cyclization of epoxide 100 to fused benzo[f>]thiophene 101 mediated by boron trifluoride-etherate . 

A closer examination by ex situ analysis using NMR or gas chromatography illustrates that intrazeolite reaction mixtures can get complex. For example photooxygenation of 1-pentene leads to three major carbonyl products plus a mixture of saturated aldehydes (valeraldehyde, propionaldehyde, butyraldehyde, acetaldehyde)38 (Fig. 33). Ethyl vinyl ketone and 2-pentenal arise from addition of the hydroperoxy radical to the two different ends of the allylic radical (Fig. 33). The ketone, /i-3-penten-2-one, is formed by intrazeolite isomerization of 1-pentene followed by CT mediated photooxygenation of the 2-pentene isomer. Dioxetane cleavage, epoxide rearrangement, or presumably even Floch cleavage130,131 of the allylic hydroperoxides can lead to the mixture of saturated aldehydes. 

Chiral Ketone from Carbohydrate. Tu et al.100 reported a dioxir-ane-mediated asymmetric epoxidation based on the ketones derived from the low cost material D-fructose (Scheme 4-47). 

All the reactions were carried out at 0°C, with the substrate (1 equivalent), ketone (3 equivalents), Oxone (5 equivalents), and NaHCC>3 in CH3CN aqueous EDTA for 2 hours. High enantioselectivity can generally be obtained for trans- and trisubstituted olefins. The favored spiro and planar transition states have been proposed for ketone 130-mediated rrans-stilbene epoxidation (Scheme 4-48). 

An alternative to the synthesis of epoxides is the reaction of sulfur ylide with aldehydes and ketones.107 This is a carbon-carbon bond formation reaction and may offer a method complementary to the oxidative processes described thus far. The formation of sulfur ylide involves a chiral sulfide and a carbene or carbenoid, and the general reaction procedure for epoxidation of aldehydes may involve the application of a sulfide, an aldehyde, or a carbene precursor as well as a copper salt. This reaction may also be considered as a thiol acetal-mediated carbene addition to carbonyl groups in the aldehyde. 

In the first of these techniques the lanthanoid complex (33) (5-8 mol%) is used as the organometallic activator in cumene hydroperoxide or tert-butyl hydrogen peroxide-mediated oxidation of chalcone (epoxide yield 99 % 99 % ee) or the ketone (34) (Scheme 20)[1001. 

B. Lygo, P. G. Wainwright, Asymmetric Phase-Transfer Mediated Epoxidation of a,p-Unsaturated Ketones using Catalysts Derived from Cinchona Alkaloids , Tetrahedron Lett. 1998,39,1599-1602. 

The vinyl silane 247 was unmasked to the ketone 250 by epoxidation, subsequent ring opening of the epoxide with HF in pyridine and concurrent cleavage of the THP and TBS protecting group (Scheme 39). The Stork-Jung annulation was completed through the treatment of the diketone 250 with sodium methoxide to mediate the intramolecular aldol con-... 

Strukul and coworkers have carried out the catalytic epoxidation of a,/3-unsaturated ketones with H2O2 mediated by a series of platinum diphosphine based complexes, that confirm the ability of the Pt(II) center to increase the nucleophilicity of hydrogen peroxide . Interestingly, this transformation may be accomplished in enantioselective fashion when chiral diphosphines such as those in 53 are used (ee up to 63%). 

In recent years, dioxiranes have become workhorses for a variety of selective transformations in organic synthesis, from epoxidation of alkenes to the conversion of alcohols into fee corresponding ketones <99CJC308>. Dioxirane-mediated epoxidation continues to be the method of choice for complex substrates wife acid-sensitive functionality. Thus, fee dimethyl-dioxirane (DMD)-mediated epoxidation of the silylated stilbene lactam 159 has been reported as a key step in fee synthesis of protoberberines <99JOC877>. 

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