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

Thangeswaran Ramar, Andivelu Ilangovan, Nicholas A Meanwell, Murugaiah A M Subbaiah

The Journal of organic chemistry 2022 Nov 04

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The scope of an umpolung approach to expand synthetic access to bifunctional γ-keto hydrazine intermediates via electrophilic amination of β-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 γ-hydroxy hydrazide, γ-amino hydrazide, and heterocyclic derivatives.

Citation

Thangeswaran Ramar, Andivelu Ilangovan, Nicholas A Meanwell, Murugaiah A M Subbaiah. Electrophilic Hydrazination of Cyclopropanols Using Azodicarboxylates via Copper(II) Catalysis: An Umpolung Strategy to Access β-Hydrazino Ketone Motifs. The Journal of organic chemistry. 2022 Nov 04;87(21):14596-14608