Stereoselective Ring Contraction of Diketopiperazines into Pyrrolidine-2,4-diones

Significance

Reported here is an efficient, mild, and exceptionally stereoselective rearrangement of N-carboxy 2,5-diketopiperazines under basic conditions to substituted pyrrolidine-2,4-diones. Thus 3-alkyl piperazine-2,5-diones A in the presence of 1.1 equivalents of t-BuOK gave the ­aminotetramates B with complete retention and excellent enantioselectivities. If R = alkyl in A, complete regio­selectivity is observed based on favorable primary carbanion formation. Similar results were obtained using symmetrical substrate C. In an interesting further variation, the reaction was examined in the presence of an external electrophile (R²X) on substrate D and gave E in a tandem rearrangement-alkylation sequence with high regio- and cis-diastereoselectivity.