Cobalt-Catalyzed Asymmetric Cyclopropanation of Heteroaryl Alkenes with Homogeneous Zinc Carbenoids

Heteroaryl-functionalized chiral cyclopropanes are commonly found in pharmaceutically relevant molecules, yet their synthesis through catalytic asymmetric cyclopropanation presents multifaceted challenges concerning enantioselectivity, safety, and scalability. Herein, we report a homogeneous catalytic asymmetric cyclopropanation method by merging chiral pyridine bis-oxazoline (PyBox)-cobalt catalysts with readily accessible zinc carbenoids. This method enables facile access to chiral cyclopropanes bearing pyridyl, pyrimidyl, and other nitrogen-containing heterocyclic substituents with high enantioselectivities. Mechanistic studies support the direct transmetallation of the zinc carbenoid to the cobalt catalyst which then participates in cyclopropanation through a redoxneutral Co II catalytic cycle. The high enantioselectivity, homogeneity, and compatibility with various green solvents render this method amenable to scale up and application across diverse heteroaryl substrates.