Towards a new class of chiral Fe-catalysts for the enantioselective hydrogenation of ketones

Asymmetric catalysis is the most efficient strategy for producing enantiopure compounds, and the enantioselective reduction of double bonds (hydrogenation in particular) is one of its most well-developed applications. Compared to other transition metals, Fe is significantly less exploited for the homogeneous catalysis of double bond reductions. However, given the far lower cost and greater abundance of Fe over the more precious metals, in recent years there has been a growing interest for developing efficient and selective homogeneous Fe-catalysts.1 Despite these efforts, only a few efficient enantioselective reduction methodologies based on Fe-catalysis have been developed so far. To fill this gap, we are developing new chiral catalysts for the enantioselective hydrogenation of ketones. We took inspiration from the Knölker-Casey catalyst 2a,2 an achiral Cp-Fe(II) hydride that can be generated in situ from the air-stable Fe(0)-cyclopentadienone precursor 1a.3 Catalyst 2a can promote the hydrogenation of ketones and imines with very high efficiency (up to 3,800 TON). Chiral cyclopentadienone complexes 1b were obtained by replacing the six-membered fused ring of 1a with a BINOL-derived chiral moiety. Complexes 2b, formed in situ from 1b using known procedures,3 showed ability to promote the hydrogenation of acetophenone with good conversions and promising enantioselectivity (up to 50% e.e.). The synthesis of improved, second-generation catalysts is currently underway. References 1. M. Darwish, M. Wills, Catal. Sci. Technol. 2012, 2, 243-255. 2. A. Quintard, J. Rodriguez, Angew. Chem. Int. Ed. 2014, 53, 4044-4055. 3. S. Fleischer, S. Zhou, K. Junge, M. Beller, Angew. Chem. Int. Ed. 2013, 52, 5120-5124. Acknowledgements: This work was funded by the European Commission [EID-ITN Network ‘REDUCTO’, contract n. PITN-GA-2012-316371] and Consiglio Nazionale delle Ricerche (CNR). L.P. thanks the Dipartimento di Chimica, Università di Milano, for financial support (Piano di sviluppo dell’Ateneo—anno 2014—Linea B.1—grants for young researchers).