Cleavage acidic, tert-alkyl esters

Fig. 6. 23. AflLl mechanism of the acidic cleavage of tert-alkyl esters.

In the absence of the activating second carbonyl functionality, it is necessary to use more ingenious methods to produce the same net effect. These procedures more often than not involve radical reactions. Among them is the thermolysis of tert-butyl esters of peroxyacids 437, which are readily synthesized in a standard esterification of tert-butyl hydroperoxide with an acid chloride. Decarboxylation proceeds via an initial homolytic cleavage of the 0-0 bond, elimination of CO2, and reduction of the incipient alkyl radical by an added hydrogen atom donor such as 438 (Scheme 2.143). Examples showing the exceptional synthetic importance of this decarboxylation procedure will be presented later. 

The reaction proved to be quite flexible both electron-rich and electron-poor substituted benzanilides worked well, as did heteroaroyl anilides, saturated heterocycle anilides, and alkyl anihdes. The presence of competitive acidic a-hydrogens or of a,P-unsaturated acyl residues did not lead to good results. For greater diversity, the cyano group of the original aniline could be efficiently replaced by a tert-butyl ester or a dimethylamide. Cleavage from the resin was performed with GH2Gl2/TFA/triethylsilane (94 5 1, v/v/v). The product (603) was then dried in vacuo at 40 °C. 

This intermediate was alkylated with tert. -butyI-cj-iodohexanoate to the ester 30. Conversion to the acid 31 was achieved by cleavage of the fed.-butylester with trifluoroacetic acid at low temperature. The triple bond was reduced to a trans-double bond and simultanously the benzylether groups had been removed with lithium in ethylamine, under formation of the desired 15-deoxy-7-oxaprostaglandin Fla 32 in crystalline form. The ds-isomer was prepared by first reducing the triple bond of compound 30 with palladium on barium sulfate to 33, removal of the ted. -butylgroup with formic acid to 34 and debenzylation of the acid with lithium in ethylamine to 35. 

The presence of carbon dioxide among the products of the reaction of teff-butyldifluoramine with excess nitric acid is a clear indication that C—C bond cleavage occurred. The nitrate and nitrite esters produced in this experiment were mixtures of various alkyl derivatives, and not solely tert-butyl derivatives as in the other cases where nitrate esters were detected. The relative stability of tritvldifluoramine toward oxidative cleavage is fully in accord with known differences between aromatic and aliphatic systems. 

---