Synthesis of 9-(Piperidin-3-yl)purine Derivatives via [4 + 2] Cycloaddition of Aza-π-allylpalladium 1,4-Dipole.

The synthesis of 9-(piperidin-3-yl)purines is reported via a [4 + 2] cycloaddition reaction of 2-(purin-9-yl)propenone derivatives with aza-π-allylpalladium 1,4-dipole derived in situ from p-toluenesulfonamide-substituted acyclic allylic carbonate. The method features a broad substrate scope, and synthetic transformations of the products further demonstrate their utility. The enantioselective cycloaddition was also demonstrated with up to 60% ee. Preliminary in vitro tests showed that compound 3f exhibits potent antitumor activity (IC50 = 2.02 μM for HCT116; IC50 = 0.73 μM for HeLa), indicating these derivatives hold strong potential for antitumor drugs.