α-Pyrones. V. The synthesis of bufadienolides. Part IV

Abstract

Additions of preformed enolate ions, derived from esters, to α-methylene carbonyl compounds, the methylene group of which carnes in the terminal position a leaving group, were studied. The reaction of steroidal 20-chloromethylene 21-aldehydes with preformed diethyl sodiomalonate results in a Michael addition which allowed an efficient synthesis of a 23-alkoxycarbonyl bufadienolide. In contrast, the reactions of the same chloromethylene aldehydes and of an analogous 20-methoxymethylene 21-aldehyde with ethyl lithioacetate give rise to 1,2-additions. The reaction of lithioacetate with the methoxymethylene aldehyde was used for the most efficient bufadienolide synthesis yet realized. Treatment with lithioacetate of 20-acetoxymethylene and 20-hydroxymethylene 21-aldehydes gave no addition products. The reactions of preformed sodiomalonate and lithioacetate with α-chloromethylene and α-methoxymethylene cyclohexanones proceeded analogously to those of the steroidal aldehydes.