Search for: All records

Abstract Olefin carbofunctionalization reactions are indispensable tools for constructing diverse, functionalized scaffolds from simple starting materials. However, achieving precise control over regioselectivity in intermolecular reactions remains a formidable challenge. Here, we demonstrate that using PAd₂ⁿBu as a ligand enables regioselective heteroannulation ofo-bromoanilines with branched 1,3-dienes through ligand control. This approach provides regiodivergent access to 3-substituted indolines, showcasing excellent regioselectivity and reactivity across a range of functionalized substrates. To gain further insights into the origin of selectivity control, we employ a data-driven strategy, developing a linear regression model using calculated parameters for phosphorus ligands. This model identifies four key parameters governing regioselectivity in this transformation, paving the way for future methodology development. Additionally, density functional theory calculations elucidate key selectivity-determining transition structures along the reaction pathway, corroborating our experimental observations and establishing a solid foundation for future advancements in regioselective olefin difunctionalization reactions. 

Abstract Typical approaches to heterocycle construction require significant changes in synthetic strategy even for a change as minor as increasing the ring size. The ability to access multiple heterocyclic scaffolds through a common synthetic approach, simply through trivial modification of one reaction component, would enable facile access to diverse libraries of structural analogues of core scaffolds. Here, we show that urea‐derived ligands effectively promote Pd‐mediated chainwalking processes to enable remote heteroannulation for the rapid construction of six‐ and seven‐membered azaheterocycles under essentially identical reaction conditions. This method demonstrates good functional group tolerance and effectively engages sterically hindered substrates. In addition, this reaction is applicable to target‐oriented synthesis, demonstrated through the formal synthesis of antimalarial alkaloid galipinine.