Ruthenium-Coordinated Spirolactams via Intramolecular Nucleophilic Addition to η6-Arene Metal Complexes

Abstract

Cyclohexadienyl ruthenium(II) complexes incorporating an azaspirocyclic ring system have been prepared from (η6-N-benzyl acetoacetamide)CpRu(II) precursors via an intramolecular nucleophilic aromatic addition/enolate trapping reaction sequence. The spirocyclization process was found to be applicable to a variety of alkyl-, alkoxy-, and chloro-substituted N-benzyl acetoacetamide ligands, and isolated yields of the cyclohexadienyl products ranged from 44% to 86%. In contrast, related arene ruthenium complexes prepared from benzyl acetoacetate and phenethyl acetoacetamide failed to undergo spirocyclization, but were found to participate in intramolecular SNAr reactions (leading to formation of tetralone and benzazepinone ring systems, respectively). Thus, the conformational mobility of the side chain linking the nucleophilic center to the coordinated arene ring appears to be important in governing the regioselectivity of aromatic addition in these reactions. Several spirolactam complexes were reduced with LiAlH4 to the corresponding Ru-coordinated spirocyclic amines; however, attempts to remove the cyclohexadienyl moiety from the CpRu(II) center via ligand protonation were unsuccessful.