Synthesis of Cyclopropanes via Hydrogen-Borrowing Catalysis
Jessica L. Crompton, James R. Frost, Sam M. Rowe, Kirsten E. Christensen, Timothy J. Donohoe
Abstract
Cyclopropanes are highly useful motifs that are often incorporated into drug candidates to improve potency, metabolic stability, or pharmacokinetic properties. An expedient method for the α-cyclopropanation of ketones using hydrogen borrowing (HB) catalysis is described. The transformation occurs via HB alkylation of a hindered ketone with subsequent intramolecular displacement of a pendant leaving group affording the cyclopropanated product. The leaving group can be installed in either the ketone or alcohol component of the HB system, giving access to α-cyclopropyl ketones via two complementary approaches. Conversion to the corresponding carboxylic acids can be achieved in a simple two-step sequence to afford synthetically useful 1,1-substituted spirocyclopropyl acid building blocks.