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 and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• , 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; diazocarbonyl compounds; N–H insertion reaction; N-heterocycles; Rh(II)-catalysis

• space of cereblon ligands. Research teams and pharmaceutical companies worldwide are actively conducting studies to discover new CRBN ligands based on α-hetaryl-substituted glutarimides of general formula 1 (Scheme 1). Consequently, a significant number of patents describing the synthesis of new PROTAC

• molecules and CRBN ligands are being published (over 400K patents in the last 5 years according to SciFinder). Various nitrogen heterocycles were utilized as a heterocyclic moiety linked to a glutarimide core via a nitrogen atom. In addition to the phthalimide fragment, the most commonly studied ones are