Site-specific DNA post-synthetic modification via fast photocatalytic allylation†

Expanding DNA functionality has significant implications in nucleic acid chemistry, biology, and beyond. Therefore, developing new chemical tools for site-specific post-synthetic modification of nucleic acids is urgently needed. Herein, we demonstrate the first site-specific DNA post-synthetic modification via visible-light-catalyzed decarboxylative allylation. Allyl sulfone groups were introduced into DNA, not only at the terminal sites via amide formation but also at internal and terminal positions during DNA solid-phase synthesis. This visible-light-catalyzed decarboxylative allylation proceeds rapidly on DNA bearing allyl sulfone groups under open-air conditions within minutes, exhibiting excellent chemoselectivity and compatibility with various functional groups while retaining DNA integrity. Specifically, introducing allyl sulfones into DNA via solid-phase synthesis enables site-specific modification on chemically synthesized single-stranded DNA (internal and terminal positions), hybridized double-stranded DNA, and enzymatically amplified long-chain DNA under visible light irradiation. The versatile reactivity of allyl sulfone scaffolds further enables diverse on-DNA photocatalytic transformations, promising to advance the chemical toolbox for DNA post-synthetic modification through diverse photochemical methods.