Nitrene Transfer-Triggered Novel Oxa−Pictet−Spengler Reaction: A Versatile Approach to Amino-Functionalized Dihydropyran Scaffolds

A novel nitrene transfer-triggered oxa−Pictet−Spengler reaction has been developed for the efficient synthesis of amino-functionalized dihydropyran scaffolds under rhodium catalysis. With Rh₂(TPA)₄ as the optimal catalyst, the reaction exhibits broad substrate scope, delivering the corresponding products (20 examples) in good yields (32%–89%). Gram-scale synthesis proceeds smoothly, and facile deprotection of the Ns group affords primary amines in good efficiency. Kinetic isotope effect studies (k_H/k_D = 2.2) reveal that C−H bond cleavage is involved in the rate-determining step. This work provides a versatile strategy for accessing amino-dihydropyran scaffolds, merging nitrene transfer with the oxa−Pictet−Spengler reaction for the first time.