Facile Assembly of Functionalizable Conjugated Dienes via Skeletal Editing of Alkynyl Diazoketones Enabled by a Traceless 2‐Pyridyloxy Group

Comprehensive Summary Herein, we report an efficient and practical strategy for the facile assembly of functionalizable conjugated dienes through skeletal editing of alkynyl diazoketones enabled by a traceless 2‐pyridyloxy group. Conjugated dienes are important structural motifs and versatile synthetic building blocks, yet the stereodefined preparation of highly substituted dienes bearing a readily transformable functional handle remains challenging. In this protocol, alkynyl diazoketones react with 2‐pyridone‐derived N,N‐ acetals under mild Lewis‐acid‐promoted conditions to furnish polysubstituted conjugated dienes with useful chemo‐, regio‐, and stereoselectivity. The readily available 2‐pyridyloxy moiety plays a dual role: it facilitates the multiple rearrangement sequence and remains in the products as a versatile handle for further diversification. The reaction exhibits broad substrate scope, tolerating alkynyl diazoketones bearing electron‐donating and electron‐withdrawing aryl substituents, heteroaryl and alkyl groups, and terminal alkynes, as well as N,N‐ acetals derived from substituted pyridones, pyrimidines, and various secondary amines. In addition, a convenient one‐pot three‐component protocol can be performed directly from an acetal amine, 2‐pyridinone, and an alkynyl diazoketone without isolation of the intermediate N,N‐ acetal. The synthetic practicality of the method is further demonstrated by gram‐scale preparation and diverse downstream transformations of the resulting dienes. In particular, the 2‐pyridyloxy group can be replaced by sulfur, aryl, and alkenyl substituents through substitution or cross‐coupling reactions, can enable installation of a complex cholesterol‐derived fragment, and can also be removed reductively. The structure of representative product 3a was confirmed by single‐crystal X‐ray diffraction, supporting the proposed connectivity and nitrogen‐initiated reaction pathway. Mechanistically, the transformation is proposed to proceed through Wolff rearrangement of the alkynyl diazoketone to an alkynyl ketene, nitrogen‐initiated nucleophilic addition of the N,N‐ acetal, subsequent 1,5‐migration to an allenamide intermediate, and a final [3,3]‐sigmatropic rearrangement to generate the conjugated diene framework. Overall, this strategy provides a modular, scalable, and practical platform for accessing structurally diverse and readily functionalizable conjugated dienes.