Triethyl Orthoformate enol ethers

Androst-4-ene-3,17-dione (83) is converted into the enol ether (84) by reaction with triethyl orthoformate. Treatment of the enol ether (84) with DDQ in aqueous acetone gives the title dienone (85). This method is particularly suitable for A" -3-ketones substituted at the 6-position. 

Stirring a mixture of a carbonyl compound, triethyl orthoformate and Amberlyst-15 at 0°-5 C gave the acetal or enol ether in good to excellent... 

Organolithium con imds also react with acetals or oithoesters in the presence of BF3-OEt2. Dialkoxymethylations of lithium enolates with triethyl orthoformate are carried out by adding BF3-OEt2 to the mixture (equation 45). Prior mixture of an enolate and the Lewis acid results in a drastic decrease of the product yield. Lithium enolates are generated from silyl enol ethers and MeLi, and C—C bond formation proceeds legiospecifically with respect to the enolates. The condensation is applicable to a fully substituted enolate. Butenolide anions add to acetals or orthoesters pretreated with BF3-OEt2 at the C-S position (equation 46). ... 

Preparation of enol ethers. Condensation of a 3-keto-5o -steroid (1) with triethyl orthoformate in ethanol containing a trace of hydrogen chloride affords the diethyl ketal (2) in good yield when refluxed in xylene the ketal loses a molecule of ethanol and affords the A -enol ether (3). A A -3-ketosteroid (4) when condensed with... 

The reaction between (2-oxoalkyl)phosphonic diesters and triethyl orthoformate in the presence of ironflll) chloride yields the enol ethyl ethers", while reactions with amines afford enamines. When heated with P4O10, enols may undergo dehydration, as in the reaction with diphenacylphosphinic acid in hot toluene, which gives the 1,4-oxaphospho-rin333". ... 

The methylmalondialdehyde acetal (38) obtained by enol ether condensation of prop-l-enyl ethyl ether (28) and triethyl orthoformate (39) is partially hydrolysed to form 2-methyl-3-ethoxypropenal (40). Reaction of 40 with sodium acetylide (41) gives 42 and acetal formation with triethyl orthoformate (39) gives 37 in an overall yield of approximately 50% (Scheme 7). 

The synthesis of 1 from the C 14-aldehyde 23 requires twenty reaction steps, including the preparation of the C6-acetal 37, and the formation of seven C-C bonds. Nevertheless, the process is economic because of the chemical and technological integration of the manufacturing process. Construction of the polyene chain, for example, only requires the simple chemicals acetylene, triethyl orthoformate, propenyl ethyl ether and vinyl ethyl ether. Five C-C bonds are formed with the aid of the enol ether condensation. This repetition of simple operations simplifies the process and allows even multistep syntheses to be carried out cost-effectively. 

Although ethisterone never attained greater medicinal importance, this compound provided the crucial hint, which led to the synthesis of norethister-one. Carl Djerassi (Fig. 6.16) at Syntex oxidised 19-nortestosterone with chromium trioxide to 19-norandrostene-3,17-dione. Treatment with triethyl orthoformate in presence of pyridinium chloride gave an enol ether, which was reacted with acetylene and potassium t-amyloxide, and could subsequently undergo acid hydrolysis to the desired product. [38]... 

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