A Hydroxypyrrole Approach to 2,2′-Bi(4-pyrrolin-3-ones) and Pyrrolone-Based α-Amino Esters

A high yield synthesis of 2-amino-4-pyrrolin-3-ones including 4-pyrrolin-3-one-based amino esters by the NBS- or TfCl-mediated reaction of 3-hydroxypyrroles with amines has been developed. The reaction of 3-hydroxypyrroles with triflyl chloride in the absence of amine affords 2,2′-bi(4-pyrrolin-3-ones) in excellent yields and diastereoselectivity. The relative configuration of stereocenters in these compounds can be changed from (2 RS,2′ RS ) to (2 RS,2′ SR ) by the action of NaH in THF, while the reverse stereoisomerization occurs in the presence of 2,5-lutidine in MeCN. Bi(4-pyrrolin-3-ones) also can be converted to 2-amino-4-pyrrolin-3-ones in excellent yields. Bi(4-pyrrolin-3-ones) and 2-amino-4-pyrrolin-3-ones were evaluated for their antiproliferative activity toward four human tumor cell lines.