Photoinduced carbonylative annulation access to β-lactams

Abstract

In radical carbonylation chemistry, orderly and sequential construction of C–C and C–N bonds with CO can effectively approach amide units and quickly incorporate a wide range of functional groups. However, this procedure remains underdeveloped for the synthesis of β-lactams. In general, especially for four-membered rings, end-to-end annulation is a thermodynamically unfavorable process compared to [2 + 2] cycloaddition. Here we developed a photoinduced radical relay carbonylative annulation (RRCA) strategy in which the key β-amino acyl radical intermediates exhibit superior capability of cyclization. This unique and underrated property is crucial in the process of successfully overcoming the tension of four-membered annulation for the synthesis of β-lactams. Mild conditions and wide substrate compatibility indicate the value of this method in the field of new drug discovery with special therapeutic effects. Particularly, embedding the amine group of the amino acid into the β-lactam skeleton further illustrates the utility of this methodology enabling late-stage modification of bioactive molecules.