Deprotection of benzyl-derived groups via photochemically mesolytic cleavage of C–N and C–O bonds

The benzyl group and its derivatives are the most frequently and widely utilized protective groups in organic synthesis and are typically removed by traditional transition-metal catalyzed hydrogenolysis or Birch reduction. The hydrogenolysis is limited by compatibility for functional groups and by the flammability and explosibility of hydrogen, while the Birch reduction suffers from flammable alkalis and harsh conditions. Here, we report that the benzyl-derived protecting groups are easily removed via visible light irradiation under mild conditions. We found that an excited phenolate-type photocatalyst efficiently transfers an electron to the benzene ring of benzyl-derived protecting groups to generate a phenyl radical anion. The benzyl C–N or C–O bond is then mesolytically cleaved by releasing a benzyl radical. This method enables efficient deprotection of the benzyl group on amides, arylamines, ether, ester, and carbamates. Specifically, this method displays excellent chemo- and regio-selectivity in carbohydrates, peptides, medicines, and natural products with multiple functionalities.