Metal‐Catalyzed Cyclization of β‐ and γ‐Allenols Derived from D‐Glyceraldehyde—Synthesis of Enantiopure Dihydropyrans and Tetrahydrooxepines: An Experimental and Theoretical Study

• Published in: Chemistry : a European journal 2009-09, Vol.15 (36), p.9127-9138
• Main Authors: Alcaide, Benito, Almendros, Pedro, del Campo, Teresa Martínez, Soriano, Elena, Marco‐Contelles, José L.
• Format: Article
• Language: English
• Subjects: allenes; cyclization; gold; palladium; platinum; reaction mechanisms
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.200901180

Regiocontrolled metal‐catalyzed preparations of enantiopure dihydropyrans and tetrahydrooxepines have been synthesized starting from β‐ and γ‐allenols derived from D‐glyceraldehyde. The PdII‐catalyzed cyclizative coupling reactions of β‐allenols 1 a and 1 b with allyl bromide effectively afforded enantiopure tetrafunctionalized dihydropyrans through a 6‐endo oxycyclization protocol, whereas the gold‐, platinum‐, and palladium‐mediated heterocyclization of γ‐allenol 2 furnished tetrahydrooxepines 13–16 through regioselective 7‐endo‐trig oxycyclization reactions. Moreover, density functional calculations were performed to predict the regioselectivity of the γ‐allenol cycloetherification to tetrahydrooxepines on the basis of both the tether nature and characteristics of the metals, and to gain an insight into the mechanism of the oxycyclization reactions. La reacción de heterociclación de β‐ y γ‐alenoles derivados de D‐gliceraldehíido catalizada por metales es un proceso regiocontrolado que da lugar a dihidropiranos y tetrahidrooxepinas enantiopuros. La reacción de ciclación/acoplamiento cruzado entre los β‐alenoles 1 a y 1 b con bromuro de alilo fue eficaz como protocolo de oxiciclación 6‐endo para dar lugar a dihidropiranos tetrafuncionalizados, mientras que las heterociclaciones del γ‐alenol 2 catalizadas por oro, platino y paladio generan las tetrahidrooxepinas 13–16 via una oxiciclación 7‐endo‐trig regioespecífica. Además, los mecanismos de estas heterociclaciones de γ‐alenoles catalizadas por metales han sido investigados teóricamente. Regiocontrolled synthesis! Enantiopure dihydropyrans and tetrahydrooxepines have been synthesized by gold‐, platinum‐, and palladium‐catalyzed regiocontrolled heterocyclization reactions starting from β‐ and γ‐allenols derived from D‐glyceraldehyde (see scheme). In addition, density functional theory (DFT) calculations were performed to obtain an insight into the various aspects of the reactivity of γ‐allenols.