Synthesis of Bicyclic Pyroglutamic Acid Featuring the Ugi Reaction and a Unique Stereoisomerization at the Angular Position by Grob Fragmentation Followed by a Transannular Ketene [2+2] Cycloaddition Reaction

Abstract A stereoisomerization at the angular position of N-acylindoles during basic hydrolysis was discovered to give only the SYN-bicyclic pyroglutamic acid, proceeding through a transannular [2+2] cycloaddition of a ketene-ketone intermediate generated by a Grob fragmentation.