Catalytic haloallylation/Zr-mediated dienyne cyclization/isomerization sequence for tailored cyclopentadiene substitution†

Abstract

The chemical properties and reactivity of cyclopentadienes (Cp) originate from the number and nature of attached functionalities. Even a slight change in their molecular architecture dramatically affects their application in organic synthesis and the performance of the respective Cp complexes in catalytic transformations. Thus, the current demand for multisubstituted cyclopentadienes requires a strategic design, allowing substituents to be installed around the Cp ring to fine-tune its reactivity profile. Herein, we present a five-step synthetic sequence that allows site-selective positioning of diverse functional groups that are otherwise difficult to attach with current methods. A judicious choice of stereoelectronically defined internal alkynes enabled regioselective bromoallylation, resulting in 1-bromo-1,4-dienes bearing three functionalities that will be part of the target Cp. Continued substitution-enrichment through the Sonogashira coupling firstly gave ornamented dienynes that upon Zr-mediated cyclization afforded a series of cyclopentenes. Finally, an acid-catalyzed exo-to-endo double bond isomerization concluded the controlled allocation of functionalities and gave a series of tetrasubstituted cyclopentadienes. Additionally, the transformability of the organozirconium intermediate enables the synthesis of bicyclic cyclopentadienes.