Enones asymmetric epoxidations

The asymmetric epoxidation of enones with polyleucine as catalyst is called the Julia-Colonna epoxidation [27]. Although the reaction was originally performed in a triphasic solvent system [27], phase-transfer catalysis [28] or nonaqueous conditions [29] were found to increase the reaction rates considerably. The reaction can be applied to dienones, thus affording vinylepoxides with high regio- and enantio-selectivity (Scheme 9.7a) [29]. 

Enders and coworkers <96AG(E)1725> have developed an interesting general one-pot method for the asymmetric epoxidation of enones with oxygen in the presence of diethylzinc and (l ,/ )-N-methylpseudoephedrine (30), which provides a, P - epoxyketones in very high yield and high enantiomeric excess (e.g., 33 —> 34). The actual reactive species is believed to be the chirally modified alkoxy(ethylperoxy)zinc 31, which attacks the si face of the s-cis conformation of the (E) enones (cf. 32). 

The epoxidation of enones with poly-D-leucine is complementary to other strategies. Enders et u/.[8] introduced a new method for the asymmetric epoxidation of a-enones using diethylzinc, oxygen and (1R, lR)-or (IS1, 2S)-N-methylpseudoephedrine as chiral auxiliary. 

B. Lygo, P. G. Wainwright Phase-Transfer Catalyzed Asymmetric Epoxidation of Enones using N-Anthracenylmethyl-Substituted Cinchona Alkaloids , Tetrahedron 1999, 55,6289-6300. 

To date the most useful and wide ranging reaction catalysed by polyamino acids is the asymmetric epoxidation of enones [22]. 

An a-substituted system (Entry 28) has also been epoxidised in good yield and with moderate stereoselectivity. Although the absolute stereochemistry of the resulting epoxide has yet to be determined, this is the first example of such an enone undergoing asymmetric epoxidation using polyamino acid catalysis. 

Compared to metal-catalyzed asymmetric epoxidation reactions, asymmetric versions of this reaction without the need of a catalyst (apart from a base) are rarely known. In 2000 Adam and coworkers reported a method for the asymmetric Weitz-Scheffer epoxidation of substituted enones 91 by the secondary, optically active hydroperoxide (5 )-(l-phenyl)ethyl hydroperoxide (equation 27, Table 10). ... 

SCHEME 47. Phase-transfer catalyzed asymmetric epoxidation of enones... 

In 1996, Enders and coworkers reported the asymmetric epoxidation of ( )-enones 91 in the presence of stoichiometric amounts of diethylzinc and (lR,2R)-A-methylpseudo-ephedrine (120) under an oxygen atmosphere to give fraw -epoxides 92 with excellent yields (94-99%), almost complete diastereoselectivity (>98% de) and with very good enantioselectivities (61-92%) (Scheme 54) . For the same reaction Pu and coworkers utilized achiral polybinaphthyl 121 as ligand (in excess) instead of the chiral aminoalcohol. For each substrate, only one diastereomer was formed, but in most cases yields were lower than observed with the Enders system. Enders catalyst shows high asymmetric induction for alkyl-substituted enones (ee 82-92%), but for substrates bearing only aromatic substituents only modest enantioselectivity was obtained (R = R = Ph ... 

SCHEME 55. Proposed reaction mechanism for the zinc-mediated asymmetric epoxidation of a, 6-enones... 

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). ... 

Maruoka and coworkers designed a new and highly efficient chiral N-spiro-type quaternary ammonium salt (S)-70 with dual functions for the asymmetric epoxidation of various enone substrates (Scheme 5.44) [45]. The exceedingly high asymmetric induction is ascribable to the molecular recognition ability of the catalyst toward enone substrates by virtue of the appropriately aligned hydroxy functionality, as well as the chiral molecular cavity. Indeed, the observed enantioselectivity depends heavily... 

J. Skidmore, and J. A. Smith, beta-Peptides as catalysts poly-beta-leudne as a catalyst for the Julia-Colonna asymmetric epoxidation of enones, Chem. Commun. 2001, (22), 2330-2331. 

As discussed in Section 10.1, asymmetric epoxidation of C=C double bonds usually requires electrophilic oxygen donors such as dioxiranes or oxaziridinium ions. The oxidants typically used for enone epoxidation are, on the other hand, nucleophilic in nature. A prominent example is the well-known Weitz-Scheffer epoxidation using alkaline hydrogen peroxide or hydroperoxides in the presence of base. Asymmetric epoxidation of enones and enoates has been achieved both with metal-containing catalysts and with metal-free systems [52-55]. In the (metal-based) approaches of Enders [56, 57], Jackson [58, 59], and Shibasaki [60, 61] enantiomeric excesses > 90% have been achieved for a variety of substrate classes. In this field, however, the same is also true for metal-free catalysts. Chiral dioxiranes will be discussed in Section 10.2.1, peptide catalysts in Section 10.2.2, and phase-transfer catalysts in Section 10.2.3. 

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],... 

In the metal-free epoxidation of enones and enoates, practically useful yields and enantioselectivity have been achieved by using catalysts based on chiral electrophilic ketones, peptides, and chiral phase-transfer agents. (E)-configured acyclic enones are comparatively easy substrates that can be converted to enantiomeri-cally highly enriched epoxides by all three methods. Currently, chiral ketones/ dioxiranes constitute the only catalyst system that enables asymmetric and metal-free epoxidation of (E)-enoates. There seems to be no metal-free method for efficient asymmetric epoxidation of achiral (Z)-enones. Exocyclic (E)-enones have been epoxidized with excellent ee using either phase-transfer catalysis or polyamino acids. In contrast, generation of enantiopure epoxides from normal endocyclic... 

In addition, solid-phase bound short-chain peptides have been recently found by the Ber-kessel group to act as highly efficient catalysts in asymmetric epoxidation reactions [17]. In the early 1980s, Julia and Colonna reported that chalcone 11 can be epoxidized asymmetrically by akaline hydrogen peroxide in the presence of poly-amino acids as catalysts [18, 19], The work by Berkessel et al. revealed that in fact as little as five I-Leu residues are sufficient for the epoxidation of the enone 11 with 96-98% ee (Scheme 8). 

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

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. 

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... 

This type of chiral lanthanum catalyst was found to be applicable for epoxidation of a range of enone substrates. Thus 35 was converted to 36 with 86% ee and in 93% yield, and 37 was transformed to 38 with 85% ee in 85% yield (Table 2, entries 1,4, and 6). The enantioselectivity of the asymmetric epoxidations could be substantially improved by the use of (/ )-3-hydroxymethyl-BINOL (32) instead of 17 (Table 2, entries 2, 3, 5, and 7). Namely, 34, 36, and 38 were obtained in excellent yields with 91, 94, and 83% ee, respectively. 

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