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. 2024 Oct 11;26(40):8527-8531.
doi: 10.1021/acs.orglett.4c03105. Epub 2024 Sep 27.

Synthesis of Monodehydro-Diketopiperazines Enabled by Cp*Rh(III)-Catalyzed Amine-Directed N-H Functionalization

Jenna C Molas  1 , Emily M Poag  1 , Jonathan A Ellman  1
Affiliations

Synthesis of Monodehydro-Diketopiperazines Enabled by Cp*Rh(III)-Catalyzed Amine-Directed N-H Functionalization

Jenna C Molas et al. Org Lett. .

Abstract

A two-step, diversity-building sequence to prepare monodehydro-diketopiperazines from readily accessible materials is reported. Rh(III)-catalyzed, amine-directed N-H functionalization of a variety of α-amino amides with a diazophosphonate ester and subsequent cyclization gives phosphonate-substituted diketopiperazines. A Horner-Wadsworth-Emmons reaction then provides monodehydro-diketopiperazines with high E-alkene selectivity. This transformation was used to incorporate a variety of groups originating from diverse aldehydes and ketones with different steric and electronic properties. Face-selective hydrogenation to diketopiperazines is also disclosed.

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Conflict of interest statement

The authors declare no competing financial interest.

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