Palladium‐Catalyzed Synthesis of Multisubstituted Conjugated Dienes from Unactivated Alkenes

The efficient and stereoselective synthesis of multisubstituted conjugated 1,3‐dienes remains a longstanding challenge because of the difficulty in controlling regioselectivity and stereochemistry. In this study, we report a ligand‐promoted, carboxylate‐directed palladium‐catalyzed alkenylation of unactivated alkenes with vinyl iodides for the modular synthesis of multisubstituted conjugated 1,3‐dienes. A bulky norbornane‐based monophosphine ligand (NBphos) is key to overcoming the intrinsically low reactivity and poor regiocontrol of unactivated alkenes, enabling efficient coupling with high regio‐ and stereoselectivity. The protocol provides access to a broad range of multisubstituted 1,3‐dienes, including highly congested pentasubstituted derivatives. Notably, stereodivergent synthesis of either diene stereoisomer is achieved directly from the corresponding E ‐ or Z ‐configured alkene substrates. The synthetic utility of the method is demonstrated through the derivatization of glycals and diverse downstream Diels–Alder transformations. Mechanistic studies reveal that a free carboxylic acid is indispensable for directing the palladium‐catalyzed alkenylation, underscoring the critical role of substrate coordination in achieving the observed reactivity and selectivity.