Dihydroquinazolinones as adaptative C(sp3) handles in arylations and alkylations via dual catalytic C–C bond-functionalization

• Published in: Nature communications Vol. 13; no. 1; pp. 2394 - 8
• Main Authors: Lv, Xin-Yang, Abrams, Roman, Martin, Ruben
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.05.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 140/131; 140/58; 639/638/77/888; 639/638/77/890; Alkylation; Bromides; Catalysis; Chemical reactions; Congeners; Coupling (molecular); Couplings; Covalent bonds; Cross coupling; Forging; Humanities and Social Sciences; Intermediates; Ketones; Modularity; multidisciplinary; Nickel; Nickel - chemistry; Oxidation-Reduction; Photochemical Processes; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-29984-0

C–C bond forming cross-couplings are convenient technologies for the construction of functional molecules. Consequently, there is continual interest in approaches that can render traditionally inert functionality as cross-coupling partners, included in this are ketones which are widely-available commodity chemicals and easy to install synthetic handles. Herein, we describe a dual catalytic strategy that utilizes dihydroquinazolinones derived from ketone congeners as adaptative one-electron handles for forging C( sp 3 ) architectures via α C–C cleavage with aryl and alkyl bromides. Our approach is achieved by combining the flexibility and modularity of nickel catalysis with the propensity of photoredox events for generating open-shell reaction intermediates. This method is distinguished by its wide scope and broad application profile––including chemical diversification of advanced intermediates––, providing a catalytic technique complementary to existing C( sp 3 ) cross-coupling reactions that operates within the C–C bond-functionalization arena. Although derived from feedstock chemicals and therefore in principle abundant, ketones are not widely used as cross-coupling partners in organic synthesis. Herein, the authors use ketone derivatives as one-electron handles for forging C(sp3) architectures via dual photo- and nickel catalysis.