Single and Consecutive Cyclization Reactions of Alkynyl Carbene Complexes and 8‐Azaheptafulvenes: Direct Access to Polycyclic Pyrrole and Indole Derivatives

• Published in: Chemistry : a European journal 2009-09, Vol.15 (35), p.8800-8806
• Main Authors: Barluenga, José, García‐Rodríguez, Jaime, Suárez‐Sobrino, Ángel L., Tomás, Miguel
• Format: Article
• Language: English
• Subjects: carbenes; chromium; cyclization; heterocycles; indole; pyrrole
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.200901257

The reactivity of alkynyl and enynyl Fischer carbene complexes towards 8‐azaheptafulvenes is examined. Alkynyl carbenes 1 a–f undergo regioselective [8+2] heterocyclization with 8‐aryl‐8‐azaheptafulvenes 2 a, b providing cycloheptapyrroles 3 and 4 with metal carbene or ester functionality at C3. Moreover, consecutive cyclization reactions are involved when enynyl carbenes are used. Thus, the cyclopenta[b]pyrrole framework 7 is formed by the consecutive [8+2] cyclization and cyclopentannulation reactions. The initially formed cyclopentannulation adduct can be intercepted through a Diels–Alder reaction with classic dienophiles to afford increasing structural complexity (compounds 8 and 9). More importantly, the construction of the indole skeleton is accomplished with a high degree of substitution and functionalization (compounds 11–15) by a one‐pot sequence that involves [8+2] cyclization, RNC or CO insertion, and ring closure. Se ha estudiado la reactividad de alquinil y eninil complejos carbeno de Fischer frente a 8‐azaheptafulvenos. Los alquinil carbenos 1 a–f experimentan una heterociclación [8 + 2] frente a 8‐aril‐8‐azaheptafulvenos 2 a–b dando lugar a cicloheptapirroles 3 y 4 conteniendo en C‐3 una función metal carbeno o éster. Además, cuando se usan eninilcarbenos se producen reacciones consecutivas de ciclación. Así, mediante reacciones consecutivas de ciclación [8 + 2] y ciclopentanulación, se forma el esqueleto de ciclopenta[b]pirrol 7. El aducto de ciclopentanulación formado inicialmente puede ser atrapado mediante una reacción Diels–Alder con dienófilos clásicos, dando lugar a una mayor complejidad estructural (compuestos 8 y 9). De mayor interés es el hecho de que se pueda llevar a cabo la construcción del esqueleto de indol con alto grado de sustitución y funcionalización (compuestos 11–15) mediante una secuencia “one‐pot” que implica una ciclación [8 + 2], inserción de R‐NC o CO y cierre de anillo. Going direct: The single [8+2] cyclization reaction of alkynyl Fischer carbene complexes and 8‐azaheptafulvenes represents a simple method of access to C3‐functionalized cycloheptapyrroles (see scheme). Moreover, enynyl carbenes provide polycyclic systems by consecutive cyclization reactions ([8+2] cyclization, cyclopentannulation, benzoannulation). Based on this protocol, indole frameworks with a high degree of substitution and functionalization are regioselectively made in a one‐pot process.