Enones epoxidation

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. 

All peptide-catalyzed enone epoxidations described so far were performed using insoluble, statistically polymerized materials (neat or on solid supports). One can, on the other hand, envisage (i) generation of solubilized poly-amino acids by attachment to polyethylene glycols (PEG) and (ii) selective construction of amino acid oligomers by standard peptide synthesis-linked to a solid support, to a soluble PEG, or neat as a well-defined oligopeptide. Both approaches have been used. The former affords synthetically useful and soluble catalysts with the interesting feature that the materials can be kept in membrane reactors for continuously oper-... 

Scheme 8. Asymmetric enone epoxidation with solid-phase bound peptide catalysts.

Fig. 1. Proposal for the mechanism of asymmetric induction in peptide-catalyzed enone epoxidations. Note that the enone carbonyl oxygen atom forms two H-bonds to the N-terminal amino acid (n) and to the one at position (n-2) a hydroperoxide anion is delivered face-selectively by NH (n-1).

Fig. 12.10 Chiral phase-transfer catalysts for enone epoxidation.

Scheme 12.12 Phase-transfer-catalyzed asymmetric enone epoxidation.

Recently, Maruoka described the novel dual function catalyst 26 bearing hydroxyl groups which were incorporated to allow hydrogen bonding to the enolate intermediate. Indeed, 26 was found to catalyze enone epoxidation with 89-99% tt [67]. Interestingly - and unlike some other systems - alkyl substitution is tolerated (Scheme 12.14). 

Scheme 12.14 Enone epoxidation with dual function phase-transfer catalyst 26.

An important recent advance in the area is the demonstration that allyl chlorides readily form allylcopper species upon exposure to highly activated copper ( Rieke copper ). The resultant allylcoppers have been shown to react with a fairly wide range of nucleophiles (ketones, aldehydes, acid chlorides, enones, epoxides [after conversion to the cuprate], imines, and allyl bromides)56. Regiochemical considerations in such substitutions depend upon the cases studied, and are fairly complex. The allylcoppers formed have, in all cases, the least substituted C—Cu bond allyl transfer from these reagents is selective from the imposition of the allyl (enone electrophiles excepted)(equations 41 and 42). The allyl chloride... 

Berkessel A, Gasch N, Glaubitz K, Koch C (2001) Highly enantioselective enone epoxidation catalyzed by short solid phase-bound peptides. Org Lett 3 3839-3842... 

The enone epoxide (169) is photochemical ly reactive and on irradiation in benzene solution afforded the six products shown in Scheme 7. The formation of products involves the photochemical formation of two intermediates (170) and (171). These thermally rearrange to the observed products with the intermediate (169) yielding (172 - 175) while intermediate (171) affords the furan (176). The complexity of these reaction paths is to be contrasted with the simpler reaction path described earlier by Mukai et aJ. ... 

In neutral media, they leave carbonyl derivatives intact but reduce tosylhydrazones to the corresponding hydrocarbons under reflux of CHCI3 (Section 3.3.4). This reduction is compatible with a-enone, epoxide, or lactone groups present in the molecule [GL3]. In cold acetone, these reagents reduce acid chlorides to aldehydes [FHl] (Section 3.2.7). In the presence of Lewis acids or gaseous HCl in CHjClj, they reduce aldehydes and ketones. The selective reduction of aldehydes in the presence of ketones can also be realized (Section 3.2.1). These reagents also reduce aromatic azides to amines (Section 5.2). 

Oxidation of Enones Epoxides and the Eschenmoser Fragmentation Part III - Electrophilic Attack on Enol(ate)s by Oxygen The Problem... 

High enantioselectivity and good yields have been obtained in asymmetric epoxidation of enones. Roberts modification of the Julia epoxidation using an immobilized polyleucine catalyst now represents a simple, practical method for enone epoxidation. Of the metal-based systems, the most economical and practical method is probably Enders protocol, despite the fact that it uses stoichiometric amounts of metal and hgand, as all the reagents are commercially available and cheap. It is difficult to compare the polypeptide-based catalysts with the metal based catalysts in terms of overall efficiency. 

Wielpiitz, T., Sottmann, T., Strey, R., Schmidt, R and Berkessel, A. (2006) Dramatic enhancement of enone epoxidation rates in nonionic microemulsions. Chem. Eur. /., 12, 7565-7575. 

A study of the photochemical behaviour of the enone epoxide (130) has been published. Several compounds (Scheme 11) are formed upon irradiation (A > 347 nm) in pentane. When the reaction is carried out in methanol these products are accompanied by the methanol addition product (131) which is proposed as good evidence for the intermediacy of the ylide (132), and the cyclopropane (133). Compounds (134) and (135), related to epoxy-enone (130), are also photoreactive and studies of these have been reported. " ... 

Ketene and the phenol (184) are formed on irradiation of the enone epoxide (185). The mechanism for the formation of the phenol remains unsure even from the results of deuterium labelling experiments. The isomeric epoxide (186) is also photoreactive and yields the three products shown in Scheme 14. The formation of the cyclopentadiene (187) is due to the thermal rearrangement of tricyclic ether... 

For epoxidation of enones and related substances with alkaline hydrogen peroxide, polyleucine exerts desirable effects, yielding products with greater than 90% ee. " Enone epoxidation with oxygen in the presence of EtjZn and R,R)-N-methylpseudoephedrine is also satisfactory. 

These bases have in recent years been utilized as stoichiometric bases in Wittig reactions [23], in Horner-Wadsworth olefinations [23] and in the synthesis of etioporphyrin from protoporphyrin [24]. Guanidines are useful as catalysts in, for example, the selective synthesis of monoglycerides [25], enone epoxidation... 

The particular value of this route to organocopper reagents is that it tolerates a wide range of functional groups enone, epoxide, carbamate, nitrile. 

Later on, they also reported an interesting intramolecular MBH reaction of an enone-epoxide system. Opening of the MBH epoxide 281 afforded homologous aldol products 282 efficiently and embodies a C(sp ) Il(sp ) coupling with concomitant cyclization. Scheme 1.102 shows a representative example. ... 

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... 

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