Direct access to α-amino amides via oxidative cleavage of alkenes

A mild and efficient metal-free oxidative Ugi-type reaction strategy is reported for the synthesis of terpenoid- α -amino acid amide derivatives. This method employs hypervalent iodine reagents to selectively cleave the inert C=C double bonds in terpenoids and other alkenes, generating aza-allenium intermediates in situ that are subsequently converted into ketimine intermediates. Under mild conditions, these ketimines undergo a multicomponent reaction with isonitriles and the carboxylic acid byproducts derived from the hypervalent iodine reagents, efficiently furnishing structurally diverse α -amino acid amide derivatives. The reaction features a broad substrate scope, tolerating various aryl/alkyl isocyanides and hydroxyl groups, and preserves the stereochemical configuration of monoterpenoids and diterpenoids. This synthetic strategy not only expands the application of C=C bond cleavage in peptidomimetic synthesis but also provides a concise approach for the high-value modification of terpenoid natural products, holding significant potential in the discovery and optimization of drug lead compounds. • Sequential reaction without work-up • In situ conversion of by-products • Facilitated pharmacophore hybridization • Significant application prospects