Acid-induced atypical spontaneous conversion of 5-amino-2,6-dioxooctahydro-1H-pyrrolo[2,1-d][1,5]oxazocine into 4-(hydroxymethyl)-2,5-dioxooctahydro-1H-pyrrolo[1,2-d][1,4]diazepine

(5 S ,8 S ,10a R )- tert -butyl 5-( tert -butoxycarbonylamino)-2,6-dioxooctahydro-1 H -pyrrolo[2,1-d][1,5]oxazocine-8-carboxylate 5 , containing an original proline-like moiety, was prepared through Yamaguchi lactonization. However, it was observed that this 8 + 5 bicyclic lactone was spontaneously rearranged to the corresponding 7 + 5 bicyclic lactam under acid conditions, used to remove the Boc/ t Bu protecting groups. Both core structures were confirmed by one-dimensional and two-dimensional NMR, as well as HRMS. The new proline-like moieties are unknown up to now, and the 7 + 5 bicyclic lactam, much more stable than its precursor, may represent a valuable template to develop constrained non-peptide mimetics.