TEMPO Mediated Cyclopropanols Ring Opening C-N Cross-Coupling with Nitrogen Nucleophiles

A feasible and umpolung strategy for the synthesis of structurally diverse beta-amino ketones has been achieved through TEMPO mediated C N coupling of cyclopropanols with nitrogen nucleophiles. Mechanism studies indicated that in situ generated enones derived from cyclopropanols are the key intermediates and TEMPO play multiple roles, including radical initiator, trapping reagent, a porter of beta-hydrogen and an in situ base. This protocol features broad substrate scope, good scalability and good to excellent yields and provides an alternative and complementary approach to the synthesis of structurally important beta-amino ketone scaffolds under metal and additive-free conditions.

Automated summary

A feasible and umpolung strategy for synthesizing diverse beta-amino ketones was achieved through TEMPO mediated C-N coupling of cyclopropanols with nitrogen nucleophiles. Mechanism studies showed that enones derived from cyclopropanols are key intermediates and TEMPO plays multiple roles. This protocol offers broad substrate scope, good scalability, and good to excellent yields, providing an alternative approach to the synthesis of structurally important beta-amino ketone scaffolds under metal and additive-free conditions.