Enones catalytic asymmetric epoxidation

D. Catalytic, asymmetric epoxidation of enones promoted by Ln-BINOL derivative complexes... 

D. Catalytic, Asymmetric Epoxidation of Enones Promoted by Ln-BINOL Derivative Complexes... 

Catalytic, asymmetric epoxidations are one of the most important asymmetric processes. In 1980 Katsuki and Sharpless reported a stoichiometric asymmetric epoxidation of allylic alcohols, a method that was later improved to become a catalytic process.9 Moreover, catalytic asymmetric epoxidations of unfunctionalized olefins using salen-manganese complexes have been reported independently by several groups.10-12 In striking contrast to these successful achievements, an efficient catalytic asymmetric epoxidation of enones with broad generality has not been developed.13-22... 

The catalytic asymmetric epoxidation of a,/5-unsaturated ketones with hydroperoxides such as tert-butyl hydroperoxide (TBHP) and cumene hydroperoxide (CMHP) can be carried out at ambient temperature by using alkali-metal free Ln-BINOL complexes (eq. (22)) [184]. The oligomeric structure of the catalyst is assumed to play a key role that is, the Ln alkoxide moiety acts as a Brpnsted base, activating a hydroperoxide molecule, while another Ln metal ion acts as a Lewis acid, both activating and controlling the orientation of the enone. 

The same kind of associative event lies at the heart of the catalytic asymmetric epoxidation of enones using the interesting binaphthyl derived spiro ammonium salt 33, which serves as a phase transfer catalyst as well as chiral auxiliary. Using sodium hypochlorite in a biphasic system, this catalyst mediates the high-yielding epoxidation of a variety of electron-deficient trisubstituted and trara-disubstituted olefins with excellent enantioselectivity, as represented by the conversion of enone 34 to the corresponding epoxy ketone 35 <04JA6844>. 

Scheme 13.35 Catalytic asymmetric epoxidation of enones using La-BINOL complexand Yb-3-hydroxymethyl BINOL complex.

From the point of view of synthesis, optically active a -epoxy carbonyl compounds of higher oxidation state, such as esters or amides, are much more useful as chiral building blocks, whereas catalytic asymmetric epoxidation of a -unsaturated esters and amides is difficult owing to lower reactivity than enones [112, 113] The problem was addressed by exploiting the unique reactivity of a -unsaturated N-acylimidazoles and N-acylpyrroles in asymmetric epoxidation with lanthanide... 

Nemoto T, Ohshima T, Shibasaki M. Enantioselective total syntheses of novel PKC activator (+)-decursin and its derivatives using catalytic asymmetric epoxidation of an enone. Tetrahedron Lett. 2000 41(49) 9569 9574. 

An overview of the results obtained for the asymmetric epoxidation of (ii)-enones 91 with the different catalytic systems is given in Table 16. 

Asymmetric epoxidation of a,jS-unsaturated ketones represents an efficient method for the preparation of optically active a,jS-epoxy ketonesJ Recently, a new and very efficient catalytic system for enantioselective epoxidation of ( )-a,jS-enones to the corresponding trans-epoxy ketones has been developed based on a BlNOL-zinc complexJ Very high yields and excellent diastereo- and enantioselectivities are achieved at room temperature using cumene hydroperoxide (CMHP) as the terminal oxidant and performing the reaction in diethyl ether. A combination of enantio-merically pure BINOL and diethylzinc readily affords the active catalyst in situ (Figure 6.13). ... 

Phase-transfer catalysis has been widely been used for asymmetric epoxidation of enones [100]. This catalytic reaction was pioneered by Wynberg et al., who used mainly the chiral and pseudo-enantiomeric quaternary ammonium salts 66 and 67, derived from the cinchona alkaloids quinine and quinidine, respectively [101-105],... 

The first part of this chapter describes recent advances in the use of novel, chiral, alkali metal free-lanthanoid-BINOL derivative complexes for a variety of efficient, catalytic, asymmetric reactions. For example, using a catalytic amount of chiral Ln-BINOL derivative complexes, asymmetric Michael reactions and asymmetric epoxidations of enones proceed in a highly enantioselective manner. 

The first catalytic asymmetric cyclopropanation using an ylide as catalyst was reported by Aggarwal et al. in 1997 [95, 96]. Phenyl diazomethane was added slowly to a mixture containing sulfide 12, an enone and Rh2(OAc)4 (1 mol%). A sulfur ylide was generated in situ from the sulfide and phenyl diazomethane in the presence of the transition-metal catalyst (see Scheme 10.20), as in the epoxidations discussed earlier (see Section 10.2.1.3). 

The conjugate addition of lithium peroxides on enones is a non-classical route to epoxidation. The original lithium enolate rearranges immediately in situU3. Note that a catalytic asymmetric version of this reaction was also developed (Scheme 41)184. 

In the presence of the sodium-containing heterobimetallic catalyst (R)-LSB (10 mol%), the reaction of enone 52 with TBHP (2 equiv) was found to give the desired epoxide with 83% ee and in 92% yield [56]. Unfortunately LSB as well as other bimetallic catalysts were not useful for many other enones. Interestingly, in marked contrast to LSB an alkali metal free lanthanoid BINOL complex, which was prepared from Ln(0- -Pr)3 and (R)-BINOL or a derivative thereof (1 or 1.25 molar equiv) in the presence of MS 4A (Scheme 17), was found to be applicable to a range of enone substrates. Regarding enones with an aryl-substitu-ent in the a-keto position, the most effective catalytic system was revealed when using a lanthanum-(.R/)-3-hydroxymethyl-BINOL complex La-51 (l-5mol%) and cumene hydroperoxide (CMHP) as oxidant. The asymmetric epoxidation proceeded with excellent enantioselectivities (ees between 85 and 94%) and yields up to 95%. 

In the asymmetric epoxidation of tra/zs-chalcone mediated by compounds Ib-d, the structure of the catalyst was found to be crucial to achieve a satisfactory level of asymmetric induction and the catalytic activity increased in the presence of the free OH group (Scheme 7.1). The epoxidation did not proceed using hydrogen peroxide or urea hydrogen peroxide as the oxidants and in the presence of an acid cocatalyst. Acceptable conversions were observed only in non polar media like hexane. Improvements in the asymmetric epoxidation of disubstituted tra/zs-enones have been achieved when using commercially available catalyst le working at 4°C (Scheme 7.3). ... 

List and coworkers reported an oxa-Michael reaction with aliphatic acyclic enones 94 using hydrogen peroxide as oxygen source [111]. Treatment of enones with catalytic amounts of cinchona alkaloid derived primary amine 33 (as its salt), followed by excess hydrogen peroxide furnished the intermediate peroxy-hemiketals with high yields and stereoselectivities. Subsequent reduction of these compounds led to the corresponding p-hydroxyketones 124 without loss of enantioselectivity (Scheme 33.36). The same research group developed the asymmetric epoxidation of enones with excellent results [112],... 

Iminium catalysis has been quite successful for asymmetric epoxidation of a,P-unsaturated carbonyl compounds, particularly, enals. Enones have remained difficult substrates. Recently, List and coworkers reported an enantioselective epoxidation of cyclic enones with either cinchona-based primary amine 38 or a counter-anion catalytic systan 149 combining a chiral vicinal diamine and a chiral phosphoric acid [69], High enantioseleclivities could be achieved in a number of cyclic enones (Scheme 5.40). 

Berkessel A, Koch B, Toniolo C, Rainaldi M, Broxterman QB, Kaptein B (2006) Asymmetric enone epoxidation by short solid-phase bound peptides further evidence for catalyst helicity and catalytic activity of individual peptide strands. Biopolymers 84 90-96... 

This kind of heterobimetallic complexes are excellent catalysts for a wide range of reactions, including epoxidation of enones, hydrophosphonylation of imines and aldehydes, and a range of asymmetric C-C bond formation reactions, involving Michael addition reaction, Diels-Alder reaction, aldol and nitroaldol reaction, etc. The alkaU metal has a profoimd effect on the catalytic property of these compounds. 

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