Studies on the oxidation of 2,2,4-trisubstituted 3-pyrrolines

As part of our studies directed towards a total synthesis of lactacystin, we have developed a reliable and environmentally acceptable method to oxidise 2,2,4-trisubstituted 3-pyrrolines to the corresponding 3-pyrrolin-2-ones. Several protocols were examined and the two-step (i) TPAP/NMO; (ii) sodium hypochlorite allylic oxidation was found to be the most satisfactory. Catalytic oxidation of the 3-pyrroline afforded the corresponding cyclic imine in high yield, and subsequent oxidation with NaOCl afforded the N-chloro-3-pyrrolin-2-one. The N-chloro-substituent was removed by a simple acid treatment.