Synthesis of\nMonodehydro-Diketopiperazines Enabled\nby Cp*Rh(III)-Catalyzed Amine-Directed N–H Functionalization

A two-step, diversity-building sequence to prepare monodehydro-diketopiperazines\nfrom readily accessible materials is reported. Rh(III)-catalyzed,\namine-directed N–H functionalization of a variety of α-amino\namides with a diazophosphonate ester and subsequent cyclization gives\nphosphonate-substituted diketopiperazines. A Horner–Wadsworth–Emmons\nreaction then provides monodehydro-diketopiperazines with high <i>E</i>-alkene selectivity. This transformation was used to incorporate\na variety of groups originating from diverse aldehydes and ketones\nwith different steric and electronic properties. Face-selective hydrogenation\nto diketopiperazines is also disclosed.