Regioselectivity Control in the Metal‐Catalyzed Functionalization of γ‐Allenols, Part 2: Theoretical Study

• Published in: Chemistry : a European journal 2009-02, Vol.15 (8), p.1909-1928
• Main Authors: Alcaide, Benito, Almendros, Pedro, Martínez del Campo, Teresa, Soriano, Elena, Marco‐Contelles, José L.
• Format: Article
• Language: English
• Subjects: allenes; cyclization; density functional calculations; gold; palladium
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.200802035

Calculating cyclization: Theoretical work directed towards the elucidation of the mechanisms of the gold‐, palladium‐, and lanthanum‐catalyzed oxycyclizations (5‐exo versus 6‐endo versus 7‐endo) of γ‐allenols has been pursued in close relationship with the experimental study (Part 1, accompanying paper) and has corroborated the bench results to provide a complete study of the reactivity of γ‐allenols under different metal‐catalyzed conditions. The gold‐, palladium‐ and lanthanum‐catalyzed oxycyclization reactions of azetidin‐2‐one‐tethered γ‐allenol derivatives to a variety of fused enantiopure tetrahydrofurans, dihydropyrans, and tetrahydrooxepines have been developed experimentally (Part 1, accompanying paper). The mechanisms of these regiocontrolled metal‐catalyzed heterocyclization reactions have now been computationally explored at the DFT level (Part 2). The energies of the reaction intermediates and transition states for different possible pathways have been calculated in various model systems very close to the real system. Additionally, we selected the La[N(SiH3)2]3 complex to simulate the lanthanide amide precatalyst species. The agreement of theoretically predicted and experimentally observed selectivities is very good in all cases La reacción de heterociclación de γ‐alenoles catalizada por metales es un proceso regiocontrolado que da lugar a una amplia variedad de tetrahidrofuranos, tetrahidropiranos y tetrahidrooxepinas fusionadas enantiopuras, que contienen además un anillo β‐lactámico, que es la unidad estructural clave en productos biológicos relevantes como antibióticos e inhibidores enzimáticos. Se ha llevado a cabo un estudio teórico para la elucidación de los mecanismos de estas ciclaciones catalizadas por oro, paladio y lantano, en estrecha relación con el trabajo experimental (Parte 1, artículo anterior), corroborando los resultados obtenidos en el laboratorio. Calculating cyclization: Theoretical work directed towards the elucidation of the mechanisms of the gold‐, palladium‐, and lanthanum‐catalyzed oxycyclizations (5‐exo versus 6‐endo versus 7‐endo) of γ‐allenols has been pursued in close relationship with the experimental study (Part 1, accompanying paper) and has corroborated the bench results to provide a complete study of the reactivity of γ‐allenols under different metal‐catalyzed conditions.