Synthesis of Cyclopropanes via Hydrogen-Borrowing Catalysis

Cyclopropanes are highly useful motifs that are oftenincorporatedinto drug candidates to improve potency, metabolic stability, or pharmacokineticproperties. An expedient method for the & alpha;-cyclopropanation ofketones using hydrogen borrowing (HB) catalysis is described. Thetransformation occurs via HB alkylation of a hindered ketone withsubsequent intramolecular displacement of a pendant leaving groupaffording the cyclopropanated product. The leaving group can be installedin either the ketone or alcohol component of the HB system, givingaccess to & alpha;-cyclopropyl ketones via two complementary approaches.Conversion to the corresponding carboxylic acids can be achieved ina simple two-step sequence to afford synthetically useful 1,1-substitutedspirocyclopropyl acid building blocks.