Enol ethers, acid-catalyzed hydrolysis

The acid-catalyzed hydrolysis of enol esters (RCOOCR =CR) can take place either by the normal Aac2 mechanism or by a mechanism involving initial protonation on the double-bond carbon, similar to the mechanism for the hydrolysis of enol ethers given in 10-6, ° depending on reaction conditions. In either case, the products are the carboxylic acid RCOOH and the aldehyde or ketone R2" CHCOR. ... 

The conversion of enol ether 80 to cyclic ketal 83 in water in 12% yield exemplifies the chemoselectivity possible with 14D9.79 Although 83 is the normal product of the acid-catalyzed hydrolysis of 80 in organic solvents, it is never observed in water because the highly reactive oxocarbenium intermediate is rapidly trapped by the solvent to give ketone 82 (via hemiacetal 81) as the sole product. The ability of the antibody to protect the reactive oxonium ion intermediate from hydrolysis and partition it toward a product that is not typically observed under these conditions (i.e., 83) mimics the capabilities of rather sophisticated enzymes. Extension to other reactions involving reactive, water-incompatible intermediates can be easily imagined. 

Baeyer-Villiger oxidation of menthone [2-methyl-5-(l-methylethyl)cyclohexanone]. Alternatively, one may first convert menthone into the silyl enol ether B and cleave its C=C double bond with ozone to obtain a bifunctional compound, which exhibits a trimethylsilyl ester and an a-methoxyhydroperoxide. The latter is reduced with NaBLLi to the hydroxylated silyl ester C. The hydroxycarboxylic acid is obtained therefrom by acid-catalyzed hydrolysis. It cyclizes spontaneously to give lactone D. 

Hoo LH, Sarkanen KV, Anderson CD (1983) Formation of C6C2-enol ethers in the acid-catalyzed hydrolysis of erythro-veratrylglycerol-/j-(2-methoxyphenyl) ether J Wood Chem Technol 3 223-243... 

TrifluoromethyUuion. Under irradiation in pyridine, the reagent reacts with a steroidal 3-ethyl enol ether (1) to give the 6-trifluoromethyl derivative (2). Acid-catalyzed hydrolysis gives the equatorial 6a-trifluoromethyl-A -3-ketosteroid (3) in good yield. 

The proposed catalytic cycle for the above-described conjugate reduction is outlined in Scheme 17. Initial coordination of the nucleophilic Pd(0)-phosphine complex to the electron-deficient olefin to form complex I is a reversible process that occurs rapidly at room temperature. Oxidative addition of the sihcon hydride moiety to complex I would result in the hydrido olefin complex II. Migratory insertion of the hydride ligand into the electrophilic /S-carbon of the coordinated olefin can result in the palladium enolate intermediate in. Reductive elimination of the silicon moiety and the enolate completes the catalytic cycle and forms the silyl enol ether IV. The latter is prone to acid-catalyzed hydrolysis to produce the saturated ketone. "" ... 

The fourth item in the table, phenol (hydroxybenzene), is alkylated on oxygen, forming an ether, methoxybenzene (anisol), with the powerful alkylating agent trimethyloxonium tetrafluoroborate [(CH30)3 BFt]. Other alkoxonium tetrafluo-roborates are also commercially available and can be used to the same end with phenols, enols, and alcohols, forming aryl ethers, enol ethers, and dialkyl ethers, respectively. In contrast to dialkyl, diaryl, and aralkyl ethers, which are quite inert and are often used as solvents, enol ethers are capable of acid-catalyzed hydrolysis to produce ketones (or their equivalent enol) and the alcohol from which the enol ether is formed (Scheme 8.47). 

Scheme 8.47. A pathway for the acid-catalyzed hydrolysis of enol ethers.

The addition of water to enol ethers causes hydrolysis to aldehydes or ketones (10-6). Ketenes add water to give carboxylic acids in a reaction catalyzed by acids " ... 

Nitroalkenes are also reactive Michael acceptors under Lewis acid-catalyzed conditions. Titanium tetrachloride or stannic tetrachloride can induce addition of silyl enol ethers. The initial adduct is trapped in a cyclic form by trimethylsilylation.316 Hydrolysis of this intermediate regenerates the carbonyl group and also converts the ad-nitro group to a carbonyl.317... 

Mukaiyama aldol condensation (6, 590-591).8 This reaction can be effected in the absence of a Lewis acid catalyst under high pressure (10 kbar). Surprisingly the stereoselectivity is the reverse of that of the TiCl4-catalyzed reaction (equation I). The reaction can also be effected in water with the same stereoselectivity, but the yield is low because of hydrolysis of the silyl enol ether. Yields are improved by use of water-oxolane (1 1) and by sonication.9... 

Step 2 Mild acid catalyzes the enol ether hydrolysis without subsequent 3, y to a, (3 alkene isomerization. 

Najera and coworkers introduced a new class of cyclic alanine templates (227, equation 59), the structure of which was anchored on Schollkopf s bislactim ether . Palladium-catalyzed allylations of the chiral pyrazinone derivative 227 with allylic carbonates (228) as substrates led to the formation of y,i5-unsaturated amino acids (229a-c) under very mild and neutral reaction conditions, whereas the required base for enolate preparation has been generated in situ from the allylic carbonate during jr-allyl complex formation. With this protocol in hand, the alkylated pyrazinones 229 were obtained with excellent regio- and diastereoselectivities (>98% ds). Finally, hydrolysis with 6 N aqueous HCl under relatively drastic conditions (150 °C) led to the free amino acids. 

A recent notable finding in this field is Mukaiyama aldol reactions in aqueous medium (THF H20 = 9 1) catalyzed by metal salts. Lewis acids based on Fe(II), Cu(II), and Zn(II), and those of some main group metals and lanthanides are stable in water. Remarkably, the aldol reaction shown in Sch. 29 occurs more rapidly than the hydrolysis of the silyl enol ether [137]. In the presence of surfactants (dodecyl sulfates or dodecane sulfonate salts), reactions of thioketene silyl acetals with benzaldehyde can be performed in water [138]. 

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