Enantioselective Synthesis of Protected Isotetronic Acids

The first highly diastereo- and enantioselective synthesis of isotetronic acids (de, ee>98 %) is reported. Key steps in the reaction sequence are the diastereoselective aldol reaction of the 2-oxoester 1 (as the SAEP hydrazone) with aldehydes, followed by base-promoted lactonization to the corresponding hydrazonolactones. Subsequent oxidative cleavage of the hydrazone moiety afforded the enantiomerically pure O-protected isotetronic acids (R)-/(S)-2.