N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N-H insertion reaction

Grigory Kantin; Pavel Golubev; Alexander Sapegin; Alexander Bunev; Dmitry Dar'in

doi:10.3762/bjoc.19.136

N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N-H insertion reaction

Beilstein J Org Chem. 2023 Dec 7:19:1841-1848. doi: 10.3762/bjoc.19.136. eCollection 2023.

Authors

Grigory Kantin¹, Pavel Golubev¹, Alexander Sapegin¹, Alexander Bunev^{1

2}, Dmitry Dar'in^{1

3

4}

Affiliations

¹ Saint Petersburg State University, Saint Petersburg, 199034, Russian Federation.
² Medicinal Chemistry Center, Togliatti State University, Togliatti, 445020, Russian Federation.
³ Saint Petersburg Research Institute of Phthisiopulmonology, Saint Petersburg, 191036, Russian Federation.
⁴ Department of Medicinal Chemistry, Institute of Chemistry, Saint Petersburg State University, 26 Universitetskiy prospekt, Peterhof 198504, Russian Federation.

Abstract

A technique has been proposed for incorporating a heterocyclic component into a glutarimide framework employing a Rh₂(esp)₂-catalyzed N-H insertion with the involvement of N-Boc-α-diazo glutarimide. The new diazo reagent is more stable, soluble and convenient to prepare than the previously suggested one. The approach permits the application of diverse heterocycles, including both aromatic and saturated NH-substrates. This yields structures that are appealing for generating cereblon ubiquitin-ligase ligands and for potential use in crafting PROTAC molecules.

Keywords: CRBN ligands; N-heterocycles; N–H insertion reaction; Rh(II)-catalysis; diazocarbonyl compounds.

Grants and funding

This research was supported by the Russian Science Foundation (project grant 22-13-00005).