Enol acetates ketones

The isoflavone 406 is prepared by the indirect a-phenylation of a ketone by reaction of phenylmercury(II) chloride with the enol acetate 405, prepared from 4-chromanone[371]. A simple synthesis of pterocarpin (409) has been achieved based on the oxypalladation of the oriho-mercurated phenol derivative 408 with the cyclic alkene 407[372,373]. 

Tin enolates of ketones can be generated by the reaction of the enol acetate 733 with tributyltin methoxide[60i] and they react with alkenyl halides via transmetallation to give 734. This reaction offers a useful method for the introduction of an aryl or alkenyl group at the o-carbon of ketones[602]. Tin enolates are also generated by the reaction of siiyl enol ethers with tributyltin fluoride and used for coupling with halides[603]. 

Another preparative method for the enone 554 is the reaction of the enol acetate 553 with allyl methyl carbonate using a bimetallic catalyst of Pd and Tin methoxide[354,358]. The enone formation is competitive with the allylation reaction (see Section 2.4.1). MeCN as a solvent and a low Pd to ligand ratio favor enone formation. Two regioisomeric steroidal dienones, 558 and 559, are prepared regioselectively from the respective dienol acetates 556 and 557 formed from the steroidal a, /3-unsaturated ketone 555. Enone formation from both silyl enol ethers and enol acetates proceeds via 7r-allylpalladium enolates as common intermediates. 

Acetic anhydride can be used to synthesize methyl ketones in Friedel-Crafts reactions. For example, benzene [71-43-2] can be acetylated to furnish acetophenone [98-86-2]. Ketones can be converted to their enol acetates and aldehydes to their alkyUdene diacetates. Acetaldehyde reacts with acetic anhydride to yield ethyhdene diacetate [542-10-9] (18) ... 

Finally, the importance of quinolinium salts to dye chemistry accounts for the long, productive history of their synthesis. The reaction of A/-methylformanihde with ketones, aldehydes, ketone enamines, or enol acetates in phosphoryl chloride leads to high yields of /V-methylquinolinium salts (60). 

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. 

The 20-ketone of an 11,20-dione has been protected as a A -enol acetate while the 11-ketone is reduced with NaBH4 in aqueous tetrahydrofuran for 9 days at room temperature. The presence of the 17(20)-double bond made possible the later introduction of a 17a-substituent. " r... 

A commonly used alternative to the direct bromination of ketones is the halogenation of enol acetates. This can be carried out under basic conditions if necessary. Sodium acetate, pyridine or an epoxide is usually added to buffer the reaction mixture. The direction of enolization is again dependent upon considerations of thermodynamic and kinetic control therefore, the proportion of enol acetates formed can vary markedly with the reaction conditions. Furthermore, halogenation via enol acetates does not necessarily give the same products as direct halogenation of ketones 3. 23... 

In the absence of steric factors e.g. 5 ), the attack is antiparallel (A) (to the adjacent axial bond) and gives the axially substituted chair form (12). In the presence of steric hindrance to attack in the preferred fashion, approach is parallel (P), from the opposite side, and the true kinetic product is the axially substituted boat form (13). This normally undergoes an immediate conformational flip to the equatorial chair form (14) which is isolated as the kinetic product. The effect of such factors is exemplified in the behavior of 3-ketones. Thus, kinetically controlled bromination of 5a-cholestan-3-one (enol acetate) yields the 2a-epimer, (15), which is also the stable form. The presence of a 5a-substituent counteracts the steric effect of the 10-methyl group and results in the formation of the unstable 2l5-(axial)halo ketone... 

Enol ethers, A -3-ketones and enol acetates have also been employed in the preparation of A -3-ketones (see also sections VI-B and VI-E) and permit the use of milder conditions than do A -3-ketones. ... 

The double bond migration which normally occurs on forming ethylene ketals from A -3-ketones has frequently been utilized to form derivatives of the A -system. The related transformation of A -3-ketones into A -3-alcohols is usually accomplished by treatment of the enol acetate (171) (X = OAc) with borohydride. This sequence apparently depends on reduction of the intermediate (172) taking place faster than conjugation ... 

Enol acetates are not very stable compounds and this limits their use as protecting groups. They are readily hydrolyzed to the parent ketones by acids and bases. 

Enol acetates are readily prepared from saturated ketones by reaction with acetic anhydride alone or diluted, in the presence of acetyl chloride ... 

Enol ethers of 17-ketones are formed by pyrolysis of the corresponding dialkyl ketals and enol acetates are readily prepared by the exchange procedure.The latter derivatives are widely used as reactive intermediates for the introduction of substituents at C-16. 

Unsubstituted 20-ketones readily form enol acetates. Reaction with isopropenyl acetate yields the kinetic A -isomer (86, R = CH3CO) which is equilibrated to the A -enol acetate (85, R = CH3CO) on exposure to acetic anhydride-/7-toluenesulfonic acid. Treatment of the 20-ketone according to the latter conditions gives the A -enol acetate directly. 

The enamines, enol ethers and enol acetates of A -3-keto steroids provide important substrates for fluorination with FCIO3. Reaction of such A -enol ethers and acetates (6) with perchloryl fluoride results in 6a- and 6jff-fluoro-A -3-ketones (7) and (8), the latter representing the more abundant isomer. Tetrahydrofuran or dioxane-water mixtures appear to be particu-... 

Isolated double bonds do not interfere with this reaction sequence, but other ketones (saturated or a, -unsaturated) will also form enol acetates, which in turn are capable of further reaction with 7V-iodosuccinimide. 

C-20 enol acetates react with peracids in the same manner as their C-17(20) counterparts, giving a 20,21-epoxide capable of cleavage to the 21-hydroxy-20-ketone ... 

The sensitivity of this ketol side chain to acid or base requires careful control of the hydrolysis of the epoxyacetate. Alternatively, the enol acetate can be brominated and the resulting bromo ketone converted to the 21-acetoxy-20-ketone ... 

Reactions of fluoroxytrifluoromethane with enol ethers, enol acetates, and enamines [/, 2, 3] are very useful, especially for the preparation of steroidal ct-fluoTo ketones (Table 2, entries 1, 3, 5, 6, and 7) [7] (equation 12)... 

The 0,N-dideuterated enol was formed by hydrolysis of the O-trimethylsilyl ether 123 (R = TMS) (in 80% [D6]DMSO/20% D2O with 5. lO " M DCl). N-Methylindoxyl (formed by hydrolysis of its acetate) exists in the solid state as a mixture of the enol and the keto tautomers (34% enol/66% keto). The NMR spectrum of freshly prepared solution in DMSO demonstrated signals of both enol and keto forms. However, at equilibrium (reached in 18 h at RT) the ratio of enol to ketone depends strongly on the polarity of the solvent used thus, in [Dg]DMSO the tautomeric mixture contains 92% enol, while in CDCI3 the keto form predominates (97%). A solution with 100% enol could be generated by hydrolysis of its O-trimethylsilyl ether [conditions 80% [Dfi]DMSO/20% D2O with 5 10" M DCl at 32°C (86TL3275 87PAC1577 88TL250)]. 

Nitradon of the potassium enolates of cycloalkanones with pentyl n silyl enol ethers with nitroniiim tetraflnoroborate " provides a method for the preparadon of cydic ct-nitro ketones. Tnflnoroacetyl nitrate generated from tnflnoroacedc anhydnde and ammonium nitrate is a mild and effecdve nitradug reagent for enol acetates fEq. 2.411. ... 

Hence, enol esters such as isopropenyl acetate are good acylating agents for alcohols. Isopropenyl acetate can also be used to convert other ketones to the corresponding enol acetates in an exchange reaction ... 

Vinylic and aryl halides can be used to vinylate or arylate carboxylic esters (but not ketones) by the use of NiBr2 as a catalyst. " However, ketones have been vinylated by treating their enol acetates with vinylic bromides in the presence of a Pd... 

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