Efficient synthesis of bioactive isoindolinone derivatives containing continuous quaternary carbons by intermolecular OH transfer

Both isoindolinones and continuous quaternary carbons play important roles in pharmaceutical scaffolds. However, few examples have been developed to construct isoindolinones containing continuous quaternary carbons due to the steric hindrance effect. Here, a rhodium(ii)-catalyzed reaction of 3-hydroxyisoindolinones and diazos via an intermolecular OH transfer to deliver the isoindolinone derivatives containing continuous quaternary carbons as products is developed in high yields of up to 89% via an intermolecular OH transfer with a green chemistry metric E-factor of 5.70. The resulting products exhibit antiviral activity against SARS-CoV-2 3CL protease (3CL^pro) and control investigations show that the quaternary carbons and hydroxyl group are essential for the bioactivity.