Organophotocatalytic N–O Bond Cleavage of Weinreb Amides: Mechanism-Guided Evolution of a PET to ConPET Platform

• Published in: ACS catalysis 2022-08, Vol.12 (16), p.10047-10056
• Main Authors: Soika, Julia, McLaughlin, Calum, Neveselý, Tomáš, Daniliuc, Constantin G., Molloy, John. J., Gilmour, Ryan
• Format: Article
• Language: English
• ISSN: 2155-5435; 2155-5435
• DOI: 10.1021/acscatal.2c02991

A mild, organophotocatalytic N–O bond cleavage of Weinreb amides is disclosed, thereby expanding the chemistry of this venerable motif beyond acylation. This redox neutral process begins to reconcile the ubiquity of N–O bonds in contemporary synthesis with the disproportionately harsh, stoichiometric conditions that are often required for bond cleavage. The strategy is compatible with the parent alkyl derivatives (N–OMe, N–OAlkyl), thereby complementing tailored O-substituent approaches that require N–OAr groups (Ar = electron-deficient). A broad range of acyclic and cyclic derivatives are disclosed (>40 examples, up to 95%), and the synthetic utility of the method is demonstrated in a range of applications. In the case of cyclic Weinreb amide derivatives, this platform enables ambiphilic amide aldehydes, of varying chain lengths, to be generated in a single transformation. Inspired by Emil Fischer’s seminal 1908 synthesis of aminoacetaldehyde using sodium amalgam, this method provides a milder route to access this important class of materials. Mechanistically guided reaction development demonstrates the involvement of a photoinduced electron transfer (PET) mechanism, and this has been further advanced to a consecutive photoinduced electron transfer (ConPET) manifold: this has significantly expanded the scope of compatible substrates.