Enones cyclic, epoxidations

Reaction with epoxides and cyclic sulfates. Opening of epoxides affords iodo-hydrins. Epoxy ketones are converted to a-iodo enones. Cyclic sulfates give alkenes. ... 

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). 

Enders found that the use of diethylzinc, oxygen and N-methylephedrine converted enones into epoxides with enantiomeric excesses of up to 92% in excellent yields (Scheme 18) [53,54]. It is believed that the zinc peroxide 10 is the intermediate in the epoxidation process. Cyclic and s-trans-enones cannot be epox-idized under these conditions. 

In 2005, Lattanzi et al. reported a series of a,a-diphenyl-L-prolinols 442 for the enantioselective epoxidation of different a,p-enones. The epoxides have been obtained in good yields and with up to 80% ee [298]. Further investigations were carried out in order to improve the enantioselectivities. On the one hand the substi-tntion pattern of the phenyl residne was tuned and on the other hand the size of the cyclic amine was modified. In these studies, the catalysts 442e-f proved to be more effective compared to other a,a-aryl-prolinols and secondary cyclic P-amino alcohols 443 and 444 (Table 7.30) [299, 303, 304]. 

The N-aminoaziridine version7 of the a,/3-epoxyketone->alkynone fragmentation is a possible alternative in situations where the simple tosylhydrazone version6-9 fails. The tosylhydrazone method often gives good yields at low reaction temperatures, but it tends to be unsuccessful with the epoxides of enones that are not cyclic or are not fully substituted at the /5-carbon atom. For example, it has been reported9 that 2,3-epoxycyclohexanone docs not produce 5-hexynal by the tosylhydrazone route. The A-aminoaziridine method can also be recommended for the preparation of acetylenic aldehydes as well as ketones. 

Interestingly, we were intrigued by the ESI mass spectrum of the compound, as the observed base peak consisted of [M-S02+Na]+. This led us to explore a thermal retro-Diels-Alder reaction that could afford the desired enone 69. It is noteworthy that the chemistry of cyclic enol-sulfites would appear to be an under-explored area with a few references reporting their isolation being found [57]. At last, we were also able to prepare epoxy ketone 70 from 69 in three steps, albeit epoxidation did not take place unless the TES group was removed. Spartan models reaffirmed our initial conformational assessment of enone 69 and epoxy ketone 70, which contain sp3-hybridized C8a and s/r-hybridized C8b (p s e u d o-. v/r - h y b r i d i zed C8b for 70) at the AB-ring junction (Fig. 8.12) and displayed the desired twisted-boat conformation in A-ring. 

The use of vinyl epoxides as substrates in enantioselective copper-catalyzed reactions, on the other hand, has met with more success. An interesting chiral ligand effect on Cu(OTf)2-catalyzed reactions between cyclic vinyloxiranes and dialkylzinc reagents was noted by Feringa et al. [51]. The 2,2 -binaphthyl phosphorus amidite ligands 32 and 43 (Fig. 8.5), which have been successfully used in copper-catalyzed enantioselective conjugate additions to enones [37], allowed kinetic resolution of racemic cyclic vinyloxiranes (Scheme 8.26). 

Reaction at the C atom of nitronate salts is known with a variety of electrophiles, such as aldehydes (Henry reaction) and epoxides (191-193). Thus the incorporation of the nitro moiety and the cyclization event can be combined into a tandem sequence. Addition of the potassium salt of dinitromethane to an a-haloaldehyde affords a nitro aldol product that can then undergo intramolecular O-alkylation to provide the cyclic nitronate (208, Eq. 2.17) (59). This process also has been expanded to a-nitroacetates and unfunctionalized nitroalkanes. Other electrophiles include functionalized a-haloaldehydes (194,195), a-epoxyaldehydes (196), a-haloenones (60), and a-halosulfonium salts (197), (Chart 2.2). In the case of unsubstituted enones, it is reported that the intermediate nitronate salt can undergo formation of a hemiacetal, which can be acetylated in moderate yield (198). 

Cyclic enol ethers such as 8 are also easily epoxidized. R. Daniel Little of the University of California, Santa Barbara has found (J. Org. Chem. 2005, 70, 5249) that such an epoxide is reduced with Tifffl) regioselectively to the radical, that adds with remarkable diastereocontrol to enones such as 7 to give the adduct 9. Reductive cyclization converted 9 to the tricyclic ether 10. The C-Br bond of 10 was stable both to the Et,SiH conditions, and to the free radical removal of the xanthate derived from the alcohol. 

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. 

Cyclic allylic cyanocuprates can also be prepared from cyclic allylic stannanes by reaction with CH3Li followed by CuCN solubilized with LiCl. These cyanocuprates couple with enones, primary and vinylic halides and epoxides (equation III).9... 

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. 

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). ... 

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