Synthesis of Functionalized Homoallylic Alcohols via a Salt‐Free Three‐Component Nickel‐Catalyzed Coupling Reaction
Year: 2025
Type: article
Abstract: In the presence of a catalytic amount (1 mol%) of Ni(cod) 2 and dppmb (1,2‐bis(diphenylphosphinomethyl)benzene)), a three‐component coupling reaction between industrially available aldehydes, buta‐1,3‐diene, and amines leads to the formation of variety of homoallylic alcohols with a highly functionalized 5‐aminopent‐3‐en‐1‐ol structure. The reaction proceeds with 100% atom economy under mild conditions (80 °C) in isopropanol as solvent. The process accommodates both aliphatic and aromatic aldehydes in combination with cyclic and acyclic secondary dialkyl amines, demonstrating a broad substrates scope. Reaction monitoring shows that the initial rate of the reaction is 39 h −1 , and the process reaches a maximum within 3 h of reaction at 80 °C. A competitive reaction has been identified as the hydroamination of 1,3‐butadiene that affords light butenylamines. The key mechanistic feature of the three‐component nickel‐catalyzed reaction is the formation of an η 3 : η 1 ‐allylalkoxy nickel (II) intermediate obtained from the oxidative coupling reaction between a low valent nickel (0) precursor, buta‐1,3‐diene, and an aldehyde. The amine subsequently reacts as a nucleophile with the electrophilic allyl moiety of this intermediate, while the alkoxy group acts as an internal base facilitating proton transfer that enables the synthesis of 5‐aminopent‐3‐en‐1‐ol derivatives without any base and salt formation.
Source: Advanced Synthesis & Catalysis
DOI: 10.1002/adsc.70183
Institutions: Centre National de la Recherche Scientifique, École Nationale Supérieure de Chimie de Lille, Université de Lille, Unité de Catalyse et Chimie du Solide, École Nationale Supérieure d'Ingénieurs de Caen, Université de Rouen Normandie, Institut National des Sciences Appliquées Rouen Normandie, Université de Caen Normandie, Miniaturisation pour la Synthèse, l'Analyse et la Protéomique
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $4,650
OpenAlex ID: W4416837343