Polymer-Assisted Solution-Phase Synthesis of the Isotetronic Acid

Significance

An easy post-treatment method using the ion-exchange resin Amberlyst for the asymmetric aldol reaction was developed. Thus, the homoaldol reaction of ethyl pyruvate 1 was catalyzed by (S)-(+)-1-(2-pyrrodinylmethyl)-pyrrodine (6)/TFA to give the crude mixture of desired isotetronic acid 2, its precursor homoaldol 3, lactone 4, and the trimer 5. The acidic resin was added to remove the catalyst 6 and promote the formation of isotetronic acid 2 and lactone 4 from 3. The basic resin also promoted the lactonization of 3 to 2 (an ammonium salt) and 4. The resulting resin-bound ammonium salt was treated with acetic acid to give isotetronic acid 2.