Dienones epoxidation

A number of papers have been devoted to aromatization reactions with enones, dienones. epoxides, etc. under a variety of experimental conditions. These reactions are beyond the scope of this Report. 

Careful re-investigation of the photolysis products of 3,5-dimethyl-y-pyrone in trifluoroethanol (reported last year ") by preparative t.l.c. (Si02) has revealed the presence of two minor, but mechanistically significant, products. One, identified as l,3-dimethyl-6-oxabicyclo[3.1.0]pent-3-en-2-one (145), is the first isolable example of the hitherto elusive cyclopentadienone epoxides, whidi have long been postulated as intermediates in these photolyses. This dienone epoxide is the photo-precursor of the final product, i.e. the isomeric 3,6-dimethyl-a-pyrone, but not of the trifluoroethanol adduct (146). This latter product, as suggested previously, derives directly from the zwitterionic precursor of the bicyclopent-3-en-2-one (145). The other product proved to be cyclopent-l-ene-3,5-dione (147), a photo-rearrangement product of (145). 

Many selective epoxidations are possible with polyunsaturated steroids. In general, oc, -unsaturated ketones are not attacked by peracid, although linear dienones react slowly at the y,5-double bond. Aw-Chloroperbenzoic acid is the reagent of choice for this reaction.When two isolated double bonds are present in the steroid nucleus, e.g. (27) and (30), the most highly substituted double bond reacts preferentially with the peracid. Selective epoxidation of the nuclear double bond of stigmasterol can likewise be achieved.However, one exception to this general rule has been reported [See (33) (34)]. ... 

Enantioselective epoxidation of unfunctionalized alkenes was until recently limited to certain ds-alkenes, but most types of alkenes can now be successfully epoxi-dized with sugar-derived dioxiranes (see Section 9.1.1.1) [2]. Selective monoepox-idation of dienes has thus become a fast route to vinylepoxides. Functionalized dienes, such as dienones, can be epoxidized with excellent enantioselectivities (see Section 9.1.2). 

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]. 

It should be noted that epoxidation of a dienone with mCPBA or other electrophilic epoxidation reagents proceeds with complementary regioselectivity, yielding y,8-epoxy enones instead of the ot,P-epoxy ketones discussed above. This feature has been utilized in several natural product syntheses Scheme 9.8 demonstrates... 

The epoxidation of the dienone 92 proceeded to give the epoxide 93 using the cinchonidinium catalyst 9 (R=H, X=C1) with tert-butyl hydroperoxide.1701... 

A novel synthesis of the sesquiterpene ( )-cinnamodial (148) utilizes the furan ring as a latent 1,4-dialdehyde synthon (81JA3226). The triol (141) was thus oxidized to the ketofuran (142). Oxidation of the furan moiety with lead tetraacetate afforded a 90% yield of epimeric diacetates (143) which when exposed briefly to DBU gave dienone (144). Epoxidation of (144) and exposure of the epoxide (145) to p-toluenesulfonic acid gave the bis-acetal (146). Reduction of this intermediate to a diol and hydrolysis of the bis-acetal furnished dialdehyde (147). Acetylation of the secondary hydroxyl group completed the synthesis of cinnamodial (Scheme 32). 

Diels-Alder reactions of a -ethenylidenecyclanonesJ These dienophiles (1) are readily obtained by reaction of lithium acetylide with epoxides followed by oxidation, but tend to polymerize when heated. Fortunately catalysts, such as BF3 etherate or ZnCl2, permit Diels-Alder reactions to proceed at low temperatures. This cycloaddition provides a regio- and stereoselective route to spirocylic dienones (2) in fair to good yield. 

This includes two new pathways in cyclohexa-2,4-dienone 4,5-epoxides, the first involving the photorearrangement of the 6,6-dimethyl derivative (115) to the enol lactone (116) via the cyclopropane(117), and the second providing the first example of a-cleavage in systems of this type. Carbon-oxygen bond homolysis is almost certainly implicated in the photorearrangement of cyclopentadienone epoxide.98... 

The manumycin family were isolated from Streptomyces parvulus (Tii 64) and possess a wide range of biological properties. Taylor and co-workers synthesized manumycin A (7) via the quinone monoacetal (131), which was prepared by PIDA oxidation, followed by epoxidation and alkylation on the cyclohexa-dienone (130) [90] (Scheme 8). Other members of the mamumycin family of antibiotics such as alisamycin, asukamycin, and ( )-nisamycin (8) have been synthesized by similar strategies [91]. 

When dienones such as 55 are subjected to the epoxidation conditions the electron-poorer C=C double bond is selectively epoxidized. The other C=C bond can be functionalized further, for example, it can be dihydroxylated, as shown in the synthesis of the lactone 56 (Scheme 10.11) [82]. Stannyl epoxides such as 57 (Scheme 10.11, see also Table 10.8, R1 = n-Bu3Sn) can be coupled with several electrophiles [72], reduction of chalcone epoxide 58 and ring opening with alkyl aluminum compounds provides access to, e.g., the diol 59 and to phenylpropionic acids (for example 60). Tertiary epoxy alcohols such as 61 can be obtained with excellent diastereoselectivity by addition of Grignard reagents to epoxy ketones [88, 89]. 

Ikegami s synthesis has two steps of particular interest. Allylation of the enolate of 27 puts the new allyl group on the outside and forces the old methyl group onto the inside 28. The planar enolate is an intermediate. The final step puts in both epoxides on the outside of the molecule from the dienone 29 mainly through complexation of VO+ with one of the free OH groups.9 This also makes both the right-hand 5/5 and the 5/3 cis fused.10... 

The ring-A/B moiety (286) of the naturally occurring C2g steroidal lactone withaferin A has been incorporated into cholestane as outlined in Scheme 14.156 Hydride reduction of the epoxide (280) gave the diol (281) which reacted stereo-specifically with peroxy-acid to yield the a-epoxide (282), and this was in turn converted into the epoxy-enone (283). The yield of (283) based upon the epoxy-dienone (261) is 70%. Ring-opening of the oxide (283) afforded the 5a-alcohol (284) which was dehydrated to the A2,5-diene (285). The A5-bond was then epox-idized stereoselectively and quantitatively to the 5/3-oxide (286). Ring A of this 5/3 -oxide was shown to be in the boat conformation. 

Dienones with extended conjugation undergo peroxy acid epoxidation regioselectively at the yiS-double bond, even if it is less substituted than the a,p-double bond. The epoxidation of (112) is regio-and stereo-selective (equation 39). Attempted epoxidation of (113a) using nucleophilic reagents furnishes polymeric materials. The epoxidation has been carried out with MCPBA (equation 40). 2a... 

Even 16-membered ring lactones, one with only two stereogenic methyl groups120, the other with six stereogenic centers, but in rather remote positions (in y,t>-position of the dienone system of a protected carbonolide117), have been epoxidized with peracid with at least 90% diastereoselectivity, the former directly to a triepoxide. 

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