Sequential Nucleophilic Addition and Regioselective Ring-Expansion Reactions of α-Diazophosphonates with Isatins: Access to 4-Phosphonylated-3-hydroxyquinolin-2(1H)-ones

ABSTRACT

A sequential protocol of α-diazophosphonates with isatins to access a series of α-diazo-β-hydroxyphosphonate derivatives via the inorganic base catalysis was reported. The resulting α-diazo-β-hydroxyphosphonates could then be readily transformed to 4-phosphonylated-3-hydroxyquinolin-2(1H)-ones with moderate to excellent yields through a catalyst-free regioselective ring-expansion rearrangement. Control experiment demonstrates that intramolecular cyclization pathway is more reasonable for the ring-expansion process. In addition, a benzo[b]thiophene-derived isatin featured with the inhibition of SARS-CoV Mpro was also suitable for this transformation and generated the corresponding scaffolds with potential anti-virus activities for further development. © 2022 Wiley-VCH GmbH.