Copper-Catalyzed Oxidative Benzylic C(sp3 )-H Cyclization for the Synthesis of β-Lactams

Abstract

β-Lactams are important structural motifs because of their ubiquity in natural products and pharmaceuticals. We report herein a Cu-catalyzed intramolecular oxidative C(sp³ )-H amidation for the synthesis of β-lactams using tBuOOtBu. This method is based on Kharasch-Sosnovsky amidation and does not require prefunctionalization of C(sp³ )-H bonds or the installation of a directing group, thereby allowing for the straightforward synthesis of β-lactams. Our intramolecular functionalization protocol can be extended to diverse benzylic C(sp³ )-H bonds and shows excellent functional-group tolerance.

Keywords: C(sp3)−H functionalization; Kharasch-Sosnovsky reaction; beta-lactam; copper; oxidation.