Catalytic Haloallylation/Zr-Mediated Dienyne Cyclization/Isomerization Sequence for Tailored Cyclopentadiene Substitution

Abstract

Chemical properties and reactivity of cyclopentadienes (Cp) originate from the number and nature of attached functionalities. Even slight change in molecular architecture dramatically reflects their application in organic synthesis and affect the performance of respective Cp-complexes in catalytic transformations. Thus, the current demand for multisubstituted cyclopentadienes requires 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. Judicious choice of stereoelectronically defined internal alkynes enabled regioselective bromoallylation resulting in 1-bromo-1,4-dienes already bearing three functionalities that will be part of target Cp. The continuing substitution-enrichment through 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.