Electrophilic Hydrazination of Cyclopropanols Using Azodicarboxylates via Copper(II) Catalysis: An Umpolung Strategy to Access β-Hydrazino Ketone Motifs

The scope of an umpolung approach to expand synthetic access to bifunctional y-keto hydrazine intermediates via electrophilic amination of fi-homoenolates derived from cyclopropanol precursors that took advantage of azodicarboxylates or azodicarboxamides as electron-deficient nitrogen sources was examined. This new synthetic procedure avails commercially available or readily accessible starting materials along with a ligand-free Cu(II) salt as an inexpensive catalyst. Using this operationally simple reaction, which proceeds under mild conditions (open-flask and ambient temperature) and is suitable for multigram scale, preparative applications were established with a range of aryl-and alkyl-substituted cyclopropanols and azodicarboxylate/ azodicarboxamide substrates (26 examples, 74-95% yields). Further, the obtained products have been shown to provide convenient synthetic access to y-hydroxy hydrazide, y-amino hydrazide, and heterocyclic derivatives.

Automated summary

This study demonstrates an umpolung approach to expand synthetic access to bifunctional y-keto hydrazine intermediates, using an electrophilic amination reaction. The reaction proceeds under mild conditions and allows the synthesis of various organic compounds.