Enol Esters and Ethers

Zhu and Burgess have reported an asymmetric conjugate reduction of 1,3-enol ether esters (Table 9) and 1,3-enol ether alcohols (Table 10) [72]. Initial reaction conditions reached full conversion of E-l-methoxy-l-phenylethene using ligand 9 albeit with a very low enantioselectivity of 29%. 

Asymmetric hydrogenation of vinyl ether alcohols proceeded in better selectivity than the ester counterparts, but acid sensitivity was observed for 66a-d, and a stoichiometric equivalent of potassium carbonate relative to the substrate was 

POPh2 30% conv 82% ee Full conv 95% ee 41% conv 63% ee No conv 

Cheruku et al. have investigated a series of enol esters [73, 95]. A preliminary experiment to determine the optimal protecting group with a small group of catalysts identified diphenylphosphinates as the optimal esters (Table 11). 

ThrePHOX 6b proved to be a valuable tool in the reduction of chromenes 71a-k, all of which were reduced in greater than 90% enantioselectivity. The very electron-rich thiochromene 71h required higher temperature, and lower conversion was observed, but the enantioselectivity remained in the useful range (Table 13) [96]. 

---

Due to the nonaromatic character of the oxepin system the oxepinones do not usually form stable enol structures. By O-acylation or O-alkylation, however, the enol forms can be stabilized as enol esters and ethers, respectively. A large number of substituted 1-benzoxepins have been synthesized by this route. Acetylation of l-benzoxepin-3(2//)-ones 1 and l-benzoxepin-5(2/T)-ones 3 was readily achieved with acetic anhydride in the presence of an appropriate base such as pyridine, triethylamine or sodium acetate.t5,t6 t72 176... 

Solutions of acetyl nitrate have also been used for the synthesis of a-nitroketones from enol esters and ethers. ° ... 

Enolizable compounds can be used for Meerwein reactions provided that the keto-enol equilibrium is not too far on the side of the ketone for example, P-dicar-bonyl compounds such as acetylacetone are suitable (Citterio and Ferrario, 1983). The arylation of enol esters or ethers (10.12) affords a convenient route for arylating aldehydes and ketones at the a-carbon atom (Scheme 10-48). Silyl enol ethers [10.12, R = Si(CH3)3] can be used instead of enol ethers (Sakakura et al., 1985). The reaction is carried out in pyridine. 

See Section 362 (Ester-Alkene) for the formation of enol esters and Section 367 (Ether-Alkenes) for the formation of enol ethers. Many of the methods in Section 60A (Protection of Aldehydes) are also applicable to ketones. 

Silyl enol ethers, enol esters and alkyl enol ethers of ketones and aldehydes can be C-alkylated with reactive alkylating agents in the presence of Lewis acids86-90. However, information regarding the use of these reactions for diastereoselcctive or asymmetric synthesis is still limited. 

Perhaps the most useful type of alkene substrates for these reactions are enol ethers, enol esters and vinyl sulfides. Silyl enol ethers have excellent electron-donor properties, with an ionization potential of about 8 eV and an oxidation potential in various solvents of approximately 1.0-1.5 V vs SCE161. These compounds are easily synthesized by reaction of an enolate with a chlorosilane. (A very recent report synthesized a variety of silyl enol ethers with extremely high stereochemical yield, using the electrogenerated amidate of 2-pyrolidinone as the base.)162 An interesting point is that the use of oxidative or reductive cyclization reactions allows carbonyl functionalities to be ambivalent, either oxidizable or reducible (Scheme 65)163. 

Others [180,260]). In general, enol radical cations may be obtained from either direct oxidation of stable ends or by selective oxidation of the enol tautomer of the keto/enol equilibrium. In addition it has been outlined that enol radical cations offer an access to a-carbonyl radical chemistry. Other enol systems like silyl enol ethers, enol esters and enolates similarly may open up after oxidation the chemistry of a-carbonyl radical or a-carbonyl cation intermediates, whereas enol ether oxidative a-functionalization reactions work by another route. 

Since the report by Carboni and Lindsey in 1959 on the cycloaddition reaction of tetrazines to multiple bonded molecules as a route to pyridazines, such reactions have been extensively studied. In addition to acetylenes and ethylenes, enol ethers, ketene acetals, enol esters and enamines, and even aldehydes and ketones have been used as starting materials for pyridazines. A detailed investigation of various 1,2,4, 5-tetrazines in these syntheses revealed the following facts. In [4 + 2] cycloaddition reactions of 3,6-bis(methylthio)-l,2,4,5-tetrazine with dienophiles, which lead to pyridazines, the following order of reactivity was observed (in parenthesis the reaction temperature is given) ynamines (25°C) > enamines (25-60°C) > ketene acetals (45-100°C) > enamides (80-100°C) > trimethylsilyl or alkyl enol ethers (100-140°C) > enol... 

Conversion Of Enolates to SUyl Enol Ethers, Silyl Enol Esters, and Silyl Enol Sulfonate Esters... 

The reaction of acid chlorides with zinc metal in an ethereal solvent usually resulted in esters arising from the acyl group and a portion of the solvent molecules [59, 60]. Later, Normant reported the formation of an enol ester and proposed the formation of an acylzinc followed by a 1,2-hydrogen rearrangement in zinc-oxy carbenoids (Eq. (5.54)) [61],... 

The ability of non-C2 symmetric ketones to promote a highly enantioselective dioxirane-mediated epoxidation was first effectively demonstrated by Shi in 1996 [114]. The fructose-derived ketone 44 was discovered to be particularly effective for the epoxidation of frans-olefins (Scheme 17 ). frans-Stilbene, for instance, was epoxidized in 95% ee using stoichiometric amounts of ketone 44, and even more impressive was the epoxidation of dialkyl-substituted substrates. This method was rendered catalytic (30 mol %) upon the discovery of a dramatic pH effect, whereby higher pH led to improved substrate conversion [115]. Higher pH was proposed to suppress decomposition pathways for ketone 44 while simultaneously increasing the nucleophilicity of Oxone. Shi s ketone system has recently been applied to the AE of enol esters and silyl enol ethers to provide access to enantio-enriched enol ester epoxides and a-hydroxy ketones [116]. Another recent improvement of Shi s fructose-derived epoxidation reaction is the development of inexpensive synthetic routes to access both enantiomers of this very promising ketone catalyst [117]. 

Enolates from Enol Esters and Silyl Enol Ethers 184... 

Diacetone alcohol [123-42-2] (4-hydroxy-4-methyl-2-pentanone) is an almost odorless ketone alcohol that is weakly acidic as a result of rearrangement to the enol form. It is miscible with water and organic solvents except aliphatic hydrocarbons. It acts as a good solvent for cellulose esters and ethers, alcohol-soluble resins, castor oil, and plasticizers. Poly(vinyl acetate) and chlorinated rubber are partially dissolved or swollen. Polystyrene, poly(vinyl chloride), vinyl chloride copolymers, dam-ar resins, resin esters, rubber, bitumen, mineral oils, ketone resins, and maleate resins are insoluble. Diacetone alcohol is used as a high boiler in stoving enamels to improve flow and gloss. 

Both enol esters and enol ethers (vinylogous esters) undergo similar intramolecular photocycloaddtions, but enol esters have advantage over enol ethers in terms of fragmentation process. Fragmentation of the cyclobutane photoadducts from enol esters is conveniently carried out under basic conditions, whereas that from enol ethers often requires additional operation to convert ether to ester or lactone (vide infra). For this reason, enol esters are more widely used than enol ethers. 

---