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

TL;DR

A chiral cobalt porphyrin catalyst enables efficient and selective C–H alkylation to form rings in quinazolinones.

Contribution

A nonsymmetric chiral cobalt porphyrin enables enantioselective intramolecular C–H alkylation with high yields and enantiomeric excess.

Findings

Formation of five-, six-, and seven-membered rings was achieved with 72–99% yield and 47–99% ee.

The catalyst uses two-point hydrogen bonding to recruit substrates and forms a cobalt-entangled carbon-centered radical.

A sequence of hydrogen abstraction and homolytic substitution is orchestrated by the chiral confinement of the catalyst.

Abstract

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.

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