Reactions that cleave C–C bonds and enable functionalization
at both carbon sites are powerful strategic tools in synthetic chemistry.
Stereodefined cyclopropyl ketones have become readily available and
would be an ideal source of 3-carbon fragments, but general approaches
to net C–C activation/difunctionalization are unknown. Herein,
we demonstrate the cross-coupling of cyclopropyl ketones with organozinc
reagents and chlorotrimethylsilane to form 1,3-difunctionalized, ring-opened
products. A combination of experimental and theoretical studies rules
out more established mechanisms and sheds light on how cooperation
between the redox-active terpyridine (tpy) ligand and the nickel atom
enables the C–C bond activation step. The reduced (tpy·–)NiI species activates the C–C
bond via a concerted asynchronous ring-opening transition state. The
resulting alkylnickel(II) intermediate can then be engaged by aryl,
alkenyl, and alkylzinc reagents to furnish cross-coupled products.
This allows quick access to products that are difficult to make by
conjugate addition methods, such as β-allylated and β
-benzylated enol ethers. The utility of this approach is demonstrated
in the synthesis of a key (±)-taiwaniaquinol B intermediate and
the total synthesis of prostaglandin D1.