Other Enol Ethers

Pyranoid 4-Enes and Furanoid 3-Enes (etido-Enes) 

An entirely different approach to pyranoid 4-enes depends on eliminations from 5-bromo compounds obtained from pyranoid hexuronic acid derivatives by photobromination. Treated with zinc-acetic acid, the bromide 249 gives the glycal -like 250 (62%), while the 4-acetoxy compound 251 is formed when DBU is used to promote elimination. Similarly, base treatment of penta-0-acetyl-5-bromo-/J-D-glucose with DBU causes the analogous loss of hydrogen bromide and formation of the 4-acetoxy-4-ene, but use of zinc-acetic acid affords mainly the 5-exo-methylene alkene by the alternative available elimination process.237 

Related derivatives are also available from ketopyranosyl,238 and pentopyranosyl compounds,239 and furanoid analogues, namely, 3-deoxy-3-enofuranosyl compounds, are usually made by use of eliminations from 3-esters of 1,2 5,6-diacetals of hexoses166 (see compound 151). 

The main chemical feature of the enol ethers covered in this section relates to the acid sensitivities of their glycosidic and enol ether groups. Consequently, the pyranoid and furanoid members hydrolyze readily in 

Pyranoid compounds such as 252 undergo hydroboration and hydrogenation to give mixtures of D-glucose and L-idose derivatives and their 6-deoxy analogues, respectively, the ratios depending on reaction conditions and on structural details of the substrates. Acid-catalyzed hydrolysis leads to 6-deoxyaldos-5-uloses.6 

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As expected, other enol ethers work well in these procedures. For example, Jones and Selenski find that implementation of method F, which occurs by addition of MeMgBr to benzaldehyde 5 in the presence of dihydropyran (DHP) at 78 °C affords a 66% yield of the corresponding tricyclic ketal 59 with better than 50 1 endo diastereoselectivity (Fig. 4.31).27 On the contrary, Lindsey reports use of method H with the benzyl alcohol 35 and diethylketene acetal. The cycloaddition reaction occurs almost instantaneously upon deprotonation of the benzyl alcohol 35 by f-butyl-magnesium bromide in the presence of the ketene acetal and yields the corresponding benzopyran ortho ester 60 in a 67% yield.29... 

Only a few examples exist for the intermolecular trapping of allyl radicals with alkenes68,69. The reaction of a-carbonyl allyl radical 28 with silyl enol ether 29 occurs exclusively at the less substituted allylic terminus to form, after oxidation with ceric ammonium nitrate (CAN) and desilylation of the adduct radical, product 30 (equation 14). Formation of terminal addition products with /ram-con figuration has been observed for reaction of 28 with other enol ethers as well. 

The dimethoxy-compound is obtained from the bromo-ketone (321) and tri-methyl orthoformate. This reaction sequence may prove useful for regiospecific synthesis of other enol ethers, where the bromo-ketones are available. 

Not merely alkoxymethylene derivatives from compounds containing reactive methylene groups, but also other enol ethers can be cleaved by amines, e.g., 3-alkoxyacrylic esters,1096 4-pyrones,1097,1098 and furfuraldehyde.1099... 

Enol ethers are prepared by acid-catalyzed transesterification or transetherification from other enol ethers, orthoesters, ketone acetals and similar precursors with allyl alcohol. The intermediate isopyrocin (the same holds for pyrocin) [48] is cleaved with thionyl chloride to afford the substrate 35 for cyclizing 1,3-elimination (Reaction scheme 21) in the presence of base [49] without significant P-elimination. 

Other conditions ultrasound-sonication other enol-ethers... 

Enol ethers (Figure 2-58a) have two electron pairs on the oxygen atom in two different orbitals, one delocalized across the two carbon atoms, the other strictly localized on the oxygen atom (Figure 2-58b). Ionization ftom either of these two orbitals is associated with two quite different ionization potentials, a situation that cannot be handled by the present connection tables. 

The ketone is added to a large excess of a strong base at low temperature, usually LDA in THF at -78 °C. The more acidic and less sterically hindered proton is removed in a kineti-cally controlled reaction. The equilibrium with a thermodynamically more stable enolate (generally the one which is more stabilized by substituents) is only reached very slowly (H.O. House, 1977), and the kinetic enolates may be trapped and isolated as silyl enol ethers (J.K. Rasmussen, 1977 H.O. House, 1969). If, on the other hand, a weak acid is added to the solution, e.g. an excess of the non-ionized ketone or a non-nucleophilic alcohol such as cert-butanol, then the tautomeric enolate is preferentially formed (stabilized mostly by hyperconjugation effects). The rate of approach to equilibrium is particularly slow with lithium as the counterion and much faster with potassium or sodium. 

The 7, i5-unsaturated alcohol 99 is cyclized to 2-vinyl-5-phenyltetrahydro-furan (100) by exo cyclization in aqueous alcohol[124]. On the other hand, the dihydropyran 101 is formed by endo cyclization from a 7, (5-unsaturated alcohol substituted by two methyl groups at the i5-position. The direction of elimination of /3-hydrogen to give either enol ethers or allylic ethers can be controlled by using DMSO as a solvent and utilized in the synthesis of the tetronomycin precursor 102[125], The oxidation of the optically active 3-alkene-l,2-diol 103 affords the 2,5-dihydrofuran 104 in high ee. It should be noted that /3-OH is eliminated rather than /3-H at the end of the reac-tion[126]. 

Silyl enol ethers are other ketone or aldehyde enolate equivalents and react with allyl carbonate to give allyl ketones or aldehydes 13,300. The transme-tallation of the 7r-allylpalladium methoxide, formed from allyl alkyl carbonate, with the silyl enol ether 464 forms the palladium enolate 465, which undergoes reductive elimination to afford the allyl ketone or aldehyde 466. For this reaction, neither fluoride anion nor a Lewis acid is necessary for the activation of silyl enol ethers. The reaction also proceed.s with metallic Pd supported on silica by a special method[301j. The ketene silyl acetal 467 derived from esters or lactones also reacts with allyl carbonates, affording allylated esters or lactones by using dppe as a ligand[302]... 

The carbonyl group forms a number of other very stable derivatives. They are less used as protective groups because of the greater difficulty involved in their removal. Such derivatives include cyanohydrins, hydrazones, imines, oximes, and semicarbazones. Enol ethers are used to protect one carbonyl group in a 1,2- or 1,3-dicarbonyl compound. 

Me3SiI, CH2CI2, 25°, 15 min, 85-95% yield.Under these cleavage conditions i,3-dithiolanes, alkyl and trimethylsilyl enol ethers, and enol acetates are stable. 1,3-Dioxolanes give complex mixtures. Alcohols, epoxides, trityl, r-butyl, and benzyl ethers and esters are reactive. Most other ethers and esters, amines, amides, ketones, olefins, acetylenes, and halides are expected to be stable. 

Generally, isolated olefinic bonds will not escape attack by these reagents. However, in certain cases where the rate of hydroxyl oxidation is relatively fast, as with allylic alcohols, an isolated double bond will survive. Thepresence of other nucleophilic centers in the molecule, such as primary and secondary amines, sulfides, enol ethers and activated aromatic systems, will generate undesirable side reactions, but aldehydes, esters, ethers, ketals and acetals are generally stable under neutral or basic conditions. Halogenation of the product ketone can become but is not always a problem when base is not included in the reaction mixture. The generated acid can promote formation of an enol which in turn may compete favorably with the alcohol for the oxidant. 

The use of A -enol ethers as substrates for dehydrogenation is often attractive. Aqueous acetone at room temperature gives yields ranging from 70 to 88% other systems with acid catalysis have also been used, e.g. ... 

FITS reagents), has undergone considerable development recently [141,142,143, 144, 14S. These compounds, available fromperfluoroalkyhodides (equation 76), are very effective electrophilicperfluoroalkylating agents They react with carban-lons, aromatic compounds, alkenes, alkynes, silyl enol ethers, and other nucleophiles under mild conditions to introduce the perfluoroalkyl moiety mto organic substrates (equation 77) (see the section on alkylation, page 446). 

More recently, further developments have shown that the reaction outlined in Scheme 4.33 can also proceed for other alkenes, such as silyl-enol ethers of acetophenone [48 b], which gives the endo diastereomer in up to 99% ee. It was also shown that / -ethyl-/ -methyl-substituted acyl phosphonate also can undergo a dia-stereo- and enantioselective cycloaddition reaction with ethyl vinyl ether catalyzed by the chiral Ph-BOX-copper(ll) catalyst. The preparative use of the cycloaddition reaction was demonstrated by performing reactions on the gram scale and showing that no special measures are required for the reaction and that the dihydro-pyrans can be obtained in high yield and with very high diastereo- and enantioselective excess. 

The monoacetate 9a (R1 = Ac) and the diacetate 10a (R1 = R2 = Ac) are obtained by treatment of 8 with acetic anhydride in anhydrous pyridine at room temperature 4 the oxo group in position 5 of 8 is more reactive towards acetylation. Similarly, the S,S-dioxidc of 8 can be converted to the bisacetylated S,5-dioxide of 10a in 78 % yield.74 Methylation of 8 with diazomethane gives 9c (65 % yield), along with 14 % of the 3-methoxy compound 11. Other alkylation agents, such as dimethyl sulfate in the presence of potassium carbonate, selectively give 9c, albeit in lower (30 %) yield.90 The dimethyl enol ether 10c (R1 = R2 = Me) is obtained by a subsequent methylation of 9c (R1 = Me) with dimethyl sulfate and potassium teri-butoxide.90... 

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