Enantioselective Intramolecular C–H Alkylation Catalyzed by a Nonsymmetric Chiral Cobalt Porphyrin

Upon catalysis (1 mol %) by a chiral cobalt porphyrin, quinazolinones with a tethered diazo alkane precursor underwent an enantioselective C–H alkylation at carbon atom C4. Formation of five-, six-, and seven-membered rings was successfully accomplished (27 examples, 72–99% yield, 47–99% ee). Experimental and computational studies suggest that the catalyst recruits the substrates by two-point hydrogen bonding. After formation of a cobalt-entangled carbon-centered radical, a sequence of hydrogen abstraction and homolytic substitution is precisely orchestrated by the chiral confinement of the cobalt porphyrin.