Epoxidation of acyclic enones

An improvement of the enantioselectivity (ee values of more than 90%) was reported independently by the Arai, Lygo, Corey, and Park-Jew groups. Arai and coworkers observed that a dramatic jump in the ee values could be achieved simply 

Quite recently, one of the most efficient phase-transfer-catalyzed epoxidation methods for chalcone-type enones was developed by the Park-Jew group [11], A series of meta-dimeric cinchona PTCs with modified phenyl linkers were prepared. Among this series, the 2-fluoro substituted catalyst 5, exhibited unprecedented activity and enantioselectivity for the epoxidation of various trans-chalcones in the 

Wang and coworkers reported the asymmetric epoxidation of chalcone derivatives using polyethylene glycol (PEG) supported cinchona-based dimeric PTCs and t rt-butyl hydroperoxide as an oxidant. However, only low to moderate ee values (33-86% ee) were obtained [12]. 

---

In this case, the O-benzyl quat hydroxide was used in conjunction with sodium hypochlorite in toluene [65]. Other reports of epoxidations of acyclic enones have appeared, showing 62% ee [66a] or lower enantioselectivity [24e,24h,48b,54a,54c-e,67],... 

Later on, Liang and coworkers successfully employed trichloroisocyanuric acid (TCCA) as a new type of stoichiometric oxidant for the asymmetric epoxidation of acyclic enones in the presence of 10 mol% of catalyst 4 (Scheme 5.6) [9]. The desired epoxy ketones were obtained in good yields (69-93%) with high enantioselectivities (73-93% ee) under nonaqueous solid-liquid conditions [9b]. In this reaction, TCCA reacts with an inorganic base (KOH) to form a hypochlorite salt, which is transferred to the organic phase by the phase-transfer catalyst and oxidizes... 

In contrast to the stereospecific epoxidation of acyclic alkenes with peroxy acids, oxidation of acyclic a,(3-unsaturated ketones with alkaline hydrogen peroxide is stereoselective in that only one stereoisomer is formed from cis- and trans-enones ... 

Soon afterward, Deng et al. adapted this primary iminium catalysis strategy for the epoxidation of acylic enones [25]. Interestingly, the treatment of the various acyclic aliphatic enones 21 with the hydroperoxides 22 in the presence of the catalyst 20 provided either the epoxides 24 or the corresponding peroxides 23... 

The asymmetric epoxidation of acyclic )S,)3-disubstituted o, )3-enones in acetonitrile, by peracetic acid and catalysed by an iron complex in which Fe(OTf)2 was coordinated by two 2-[l-(l-naphthyl)-2-naphthyl]-l,10-phenanthroline ligands (35) (R = m-xylyl), to the corresponding Q ,j8-epoxyketones with yield up to 88% and up to 92% ee was achieved. The epoxy ketone was further converted to functionalized )8-keto-aldehydes with an all-carbon quaternary centre." The transfer hydrogenation of acetophenone to 1-phenylethanol in isopropanol in the absence of added base was catalysed by a five-coordinated Fe(II) complex (36) and certain analogues. ... 

For epoxidation of chalcones using Ender s method, the results depend on the nature of the substrate. For the ( )-benzylideneacetophcnonc (R1, R2 = Ph), the enantiomeric excess was only 60 % using the same procedure as the one described above, whereas the polyleucine method furnished the epoxide with an enantiomeric excess > 95%. Table 4.3 gives some results of the epoxidation of some acyclic enones using Ender s method. 

The at complex from DIB AH and butyllithium is a selective reducing agent.16 It is used tor the 1,2-reduction of acyclic and cyclic enones. Esters and lactones are reduced at room temperature to alcohols, and at -78 C to alcohols and aldehydes. Acid chlorides are rapidly reduced with excess reagent at -78 C to alcohols, but a mixture of alcohols, aldehydes, and acid chlorides results from use of an equimolar amount of reagent at -78 C. Acid anhydrides are reduced at -78 C to alcohols and carboxylic acids. Carboxylic acids and both primary and secondary amides are inert at room temperature, whereas tertiary amides (as in the present case) are reduced between 0 C and room temperature to aldehydes. The at complex rapidly reduces primary alkyl, benzylic, and allylic bromides, while tertiary alkyl and aryl halides are inert. Epoxides are reduced exclusively to the more highly substituted alcohols. Disulfides lead to thiols, but both sulfoxides and sulfones are inert. Moreover, this at complex from DIBAH and butyllithium is able to reduce ketones selectively in the presence of esters. 

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... 

The unusual nucleophilic epoxidation of /i-hydroxyenones under Sharpless conditions (see Section 4.5.1.3.2.1.) is also applicable to compounds 1 with endocyclic double bonds. The. sj H-epoxides are produced with complete selectivity. The stereochemical outcome of the reaction under Weitz-Scheffer conditions significantly differs from that observed for acyclic compounds. While the acyclic enones afforded preferentially the moderate ratio, cyclic ones gave predominantly s>7i-epoxides32. 

For acyclic allylic alcohols, very little a,p-unsaturated enone formation was observed besides epoxidation. Chemoselectivity was much less for cyclic allylic alcohols, for which oxidation of fhe allylic alcohol group competed significantly with epoxidation. In the case of 2-cyclohexenol as the substrate, the enone was even found to be the main product. A comparative sandwich POM-catalyzed epoxidation study of various (subsfifufed) cycloalkenols revealed that the enone versus epoxide chemoselectivity is controlled by the C=C-C-OH dihedral angle Ma in the allylic alcohol substrate. The more this dihedral angle deviates from fhe optimum C=C-C-OW dihedral angle otw for allylic acohol epoxidation, the more enone is formed (Fig. 16.5). 

NAP-MgO acts as a bifunctional heterogeneous catalyst for the Claisen-Schmidt condensation (CSC) of benzaldehydes with acetophenones to yield chalcones, followed by asymmetric epoxidation (AE) to afford chiral epoxy ketones in moderate to good yields and impressive enantioselectivities (ee s). NAP-MgO, in combination with the chiral auxiliary (11 ,21 )-(- -)-1,2-diphenyl-1,2-ethylenediamine (DPED), catalyzed the asymmetric Michael addition of malonates to cyclic and acyclic enones. 

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],... 

The authors also investigated the mode of activation of these BINOL-derived catalysts. They proposed an oligomeric structure, in which one Ln-BINOL moiety acts as a Brpnsted base, that deprotonates the hydroperoxide and the other moiety acts as Lewis acid, which activates the enone and controls its orientation towards the oxidant . This model explains the observed chiral amplification effect, that is the ee of the epoxide product exceeds the ee of the catalyst. The stereoselective synthesis of cw-epoxyketones from acyclic cw-enones is difficult due to the tendency of the cw-enones to isomerize to the more stable fraw5-derivatives during the oxidation. In 1998, Shibasaki and coworkers reported that the ytterbium-(f )-3-hydroxymethyl-BINOL system also showed catalytic activity for the oxidation of aliphatic (Z)-enones 129 to cw-epoxides 130 with good yields... 

On treatment with a palladium(O) catalyst, vinyl epoxides undergo facile unimolecular rearrangement to give dienols or enones depending on the substitution pattern of the substrate. In the presence of an active methylene compound in the reaction system, however, a single alkylation product is formed. Cyclic and acyclic vinyl epoxides participate equally well. The reaction proceeds with clean alkylation from the same face as the oxygen of the epoxide, and proceeds with allyl inversion (Scheme 22). ... 

---