Visible-Light-Mediated Energy Transfer Enables the Synthesis of β-Lactams via Intramolecular Hydrogen Atom Transfer

Abstract

The synthesis of 2-azetidinones (β-lactams) from simple acrylamide starting materials by visible-light-mediated energy transfer catalysis is reported. The reaction features a C(sp³ )-H functionalization via a variation of the Norrish-Yang photocyclization involving a carbon-to-carbon 1,5-hydrogen atom transfer (supported by deuterium labelling and DFT calculations) and can be used for the construction of a diverse range of β-lactam products.

Keywords: C−H Functionalization; Energy Transfer; Heterocycles; Hydrogen Atom Transfer; Photocatalysis.

Figure 1

Representative set of biologically important β‐lactam (2‐azetidinones) and azetidine derivatives.

Scheme 1

A–C) Previous literature reports on Norrish–Yang type chemistry and related variations. D) This work.

Scheme 2

Reaction scope. ^[a] Isolated yields. ^[b] Diastereomeric ratio determined by ¹H NMR analysis of the crude reaction mixture and are given as the trans:cis ratio. ^[c] Starting material recovered.

Scheme 3

A) Proposed mechanism. B–C) Deuterium labelling studies. D) DFT studies. Energies are Gibbs free energies at 298.15 K in kJ mol⁻¹ calculated at the D3(BJ)‐UB3LYP/def2‐TZVPP//UB3LYP/def2‐SVP level of theory, with PCM solvent correction in toluene. The MECP structure and energy was found using Orca, at the D3(BJ)‐UB3LYP/G/def2‐TZVPP//UB3LYP/G/def2‐SVP level of theory, which was compared with Orca calculated energies of ³B and ¹B _s‐trans (see Supporting Information for further details).