Charge-Tagged Cyclopentadienone Iron Complexes: Mechanistic Studies Using Mass Spectrometry for Catalytic Hydrogenation Reactions

Abstract

Cyclopentadienone iron complexes, also referred to as Knölker catalysts, have emerged as promising catalysts for the reduction of ketones, aldehydes, and imines. They constitute the iron analogues to the ruthenium based Shvo catalysts and offer the possibility to enable the same chemistry as the ruthenium based system with use of a widely available first-row transition metal. While there is a consensus on the operating reaction mechanism, detailed, real-time monitoring of the catalytic cycle has not been described in the literature. To this end, we have investigated the reaction mechanism by mass-spectrometry. To make the cyclopentadienone iron complex system amenable to electrospray ionization-mass spectrometry, prosthetic charge-tags, both positive and negative ones, were introduced. These charge-tags, in combination with conventional kinetic experiments, allowed for the observation of the catalyst in the working state. The mass spectrometric studies led to the identification of a major catalyst decomposition pathway that takes place in aqueous solvent. In particular, hydrolysis of trimethylsilyl groups in the catalyst was observed, which led to dimerization, radical formation and, ultimately, to catalysts death. Replacement of the trimethylsilyl groups by nonhydrolysable tert-butyl groups lead to a significant boost in rate and to an increase in turn-over number from 65 to over 1000. In addition to the mass spectrometric and kinetic studies to investigate the reaction mechanism, an experimental study investigating the influence of the charge-tag on catalysis is presented. It was observed that negatively charge-tagged complexes generally show slower rates than the classical Knölker catalyst. Using a combination of NMR and kinetic measurements, it could be experimentally shown that binding of the charge-tag to the catalytically active site and electric field effects are not responsible for the difference in catalytic performance. The presence of a tertiary amine in the catalyst structure was identified as a possible source of the difference. Furthermore, it was found that negatively charge-tagged iron catalysts form micelles in aqueous solvent. These micelles were found to enhance catalytic performance compared to other amine containing catalysts. Neutral, isocyanide ligand-bearing cyclopentadienone iron complexes are presented in this work. These complexes generally show lower catalytic performance than the corresponding carbonyl complexes. However, the isocyanides allow for the tuning of steric and electronic properties by varying the R group on the CNR ligand, offering a new handle to tune reactivity. Furthermore, since the isocyanides can be prepared from primary amine precursors, for which many chiral ones are available, chiral iron complexes could be prepared. The complexes show very modest stereoinduction. Their syntheses, characterizations and catalytic performances will be presented and discussed.