Enantioselective synthesis of protected isotetronic acids

Isotetronic acids are subunits of a number of natural products. They are of interest in agricultural and pharmaceutical research and are important synthetic intermediates. This paper describes the first highly diastereo-and enantioselective synthesis of isotetronic acids in 4 to 5 steps (de, ee > 98 %). Key steps in the reaction sequence are the diastereoselective aldol reaction of the 2-oxoesters 5 as their SAEP hydrazones (S)-6 with aldehydes, followed by base-promoted lactonization to the hydrazonolactones 8. Subsequent oxidative cleavage of the hydrazone moiety afforded the enantiomerically pure O-protected isotetronic acids (R)-/(S)-9.