Chiral β-Lactams by Ruthenium-Catalyzed Enantioselective CH Carbene Insertion

Abstract

A ruthenium-catalyzed intramolecular carbenoid insertion into a C(sp³)H bond leads to the enantioselective formation of chiral β-lactams. The reaction is catalyzed by a ruthenium complex featuring a chiral pyridine-2,6-bis(oxazoline) ligand, combined with a cyclometalated phenylimidazo[1,5-a]pyridine ligand. This complex belongs to a recently introduced new class of ruthenium catalysts (Angew. Chem. Int. Ed. 2020, 59, 12393). Starting from N-benzyl α-diazoacetamides, chiral β-lactams are provided in up to 82% isolated yield with up to 98% enantiomeric excess, without any occurrence of a Buchner side reaction. Mechanistic experiments reveal that β-lactam (4-membered ring) formation is inherently favored over the more common γ-lactam (5-membered ring) formation.