Synthesis from enol ethers

Figure 1. Synthesis of acetals from enol ethers and diols.

Diethyl [(2-tetrahydropyranyloxy)methyl]phosphonate is useful in the Wlttig-Horner synthesis of enol ethers, which are intermediates in one-carbon homologations of carbonyl compounds. This procedure is an adaptation of a general method for making dialkyl hydroxymethylphosphonates. An 0-tetra-hydropyranyl derivative also has been made from dibutyl hydroxymethyl -phosphonate, and diethyl hydroxymethylphosphonate has been O-silylated with tert-butylchiorodimethylsilane and imidazole. Another useful congener in this series has been prepared by an Arbuzov reaction of methoxyethoxymethyl (HEM) chloride and triethyl phosphite. 

Figure 12.25 shows how acetals can be brominated electrophihcally because of the (weakly) acidic reaction conditions. Proper acidity and electrophihcity is ensured by the use of pyri-dinium tribromide (B). This reagent is produced from pyridinium hydrobromide and one equivalent of bromine. Pyridinium tribromide is acidic enough to cleave the acetal A into the enol ether G. This cleavage succeeds by way of an El elimination like the one encountered in Figure 9.32 as an enol ether synthesis. The enol ether G reacts with the tribromide ion via the bromine-containing oxocarbenium ion H and the protonated acetal D to form the finally isolated neutral bromoacetal C. (The reaction can be conducted despite the unfavorable equilibrium between the acetal A and the enol ether G, since G continuously reacts and is thus eliminated from the equilibrium.)... 

B. Synthesis of Enolates from Enol Ethers and Esters. 542... 

Tetrahydropyranyl (THP) protection of the hydroxy group of 48 yields a useful reagent for the Horner-Wadsworth-Emmons synthesis of enol ethers from carbonyl compounds.103 104... 

TABLE 3. Synthesis of a-benzylated ketones starting from enol ethers... 

The Mn(salen) complex 8 has also been appHed towards the synthesis of a-hydroxy carbonyl compounds from enol ethers and ketene acetals [87,88,89]. These substrates are a special class of trisubstituted olefins, previously demonstrated to be excellent substrates for AE. Indeed, the observed sense of stereoinduction in the oxidation of enol ether derivatives adheres to the skewed side-on approach model developed for trisubstituted olefins. In the presence of 7 mol % of 8, silyl enol ether 37 was oxidized under bleach conditions to afford the a-hy-droxy ketone in 87% ee (Scheme 14) [89]. 

The hydroboration of alkylvinyl ethers in hexane provides tris(/3-alkoxyethyl)bor-anes in high yields Controlled hydroboration conditions and rigorous exclusion of BF3 are necessary for the efficient synthesis of -alkoxyorganoboranes from enol ethers °. 

Peterson aikenation of carbonyl compounds with trimethylsilylmethoxymethyl carbanion (14) can also give enol ethers. An example is the reaction of (14) with adamantanone. Another method of alkene synthesis is the elimination of CO2 and H2O from a P-hydroxycarboxylic acid. If the carboxylic acid is substituted by an a-alkoxy group, the reaction can be used for the synthesis of enol ethers, as illustrated in Scheme 4. ... 

Dicarbonyl Compounds.—Ozonolysis of 2-cyclopentylidenecyclopentanone provides a convenient synthesis of cyclopentane-l,2-dione on the ca. 0.4 mole scale.The by-product, cyclopentanone, is recycled via an aldol condensation to regenerate the enone. The method should be applicable to other alicyclic 1,2-diones. Various methods for the preparation of monoprotected 1,2-diones have appeared. Monoacetals of a-dicarbonyl compounds are prepared regio-specifically from enol ethers [equation (32)], following epoxidation in methanol and oxidation of the resulting acyloin acetal. 

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]. 

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