Asymmetric ketone and imine reductions using ruthenium catalysts

1. Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK J.P.Hopewell@Warwick.ac.uk Introduction • This poster is concerned with the asymmetric reduction of ketones and imines • Previous work in group has led to success with ruthenium based catalysts 1 and 21-5 • It has previously been demonstrated that the Shvo catalyst 3 is an efficient transfer hydrogenation catalyst 6,7 • It would be of great interest to synthesise and test asymmetric derivatives of the Shvo catalyst in asymmetric transfer hydrogenation Asymmetric ketone and imine reductions using ruthenium catalysts Ruthenium catalyst synthesis Hydridesynthesis • The metal hydide of complex 6 showed unusually highfield signal compared to all the other hydride complexes at -17 ppm • This is indicative of a bridging hydride complex as observed in the Shvo catalyst6 • Integration of the hydride signal also indicates a 1:2 ratio of hydride to ligand as further evidence of a bridging hydride formation • In order to screen in hydrogenation catalysis, activated hydride species of complexes 4-11 were synthesised • The ruthenium hydrides complexes were generated using NaOH followed by phosphonic acid quench9 • The precatalyst hydrides were observed by the characteristic signal in their 1H NMR spectrum at between -9 to -11 ppm9 Crystal structure of symmetric complex 5 Synthesis of complexes 7 - 12 affords a mixture of two products in varying ratios (3:1 to 10:1) depending on the R’ and R’’ groups present. The major product is assumed to be the isomer with the R group on the furan backbone pointing away from the Ru metal centre. Jonathan Hopewell, José E. D. Martins and Martin Wills* Hydrogenation of ketones Hydrogenation of imines • In transfer hydrogenation catalysts 7, 9 and 11 exhibited the highest activities both systems • For pressure hydrogenations catalysts 5, 7, 9 and 11 proved the most active. • For the asymmetric catalysts only 7 exhibited no selectivity with modest ees being observed for all the other catalysts in all three hydrogenation methods • ATH reactions took upwards of 100 h to near completion Hydrogenation results • Catalysts 4 – 11 were screened in asymmetric transfer hydrogenation as well as pressure hydrogenation of acetophenone • ATH was achieved using either iPrOH or formic acid/triethylamine azeotrope as the hydrogen source and solvent at 60°C with 0.5 mol% catalyst loading • The pressure hydrogenation reductions were carried out using 35 bar H2 gas at 30°C in toluene over 24 h 5 mol% catalyst loading9 • Conversions and, in the case of the asymmetric catalysts, ees were determined by chiral GC 28°C, 22 h, 0.5 mol% catalyst in 5:2 FA/TEA and acetonitrile Using catalysts 8 and 9 successful asymmetric reduction of the above cyclic imine was achieved with moderate yields of >60% and ees similar to those observed for the reductions of acetophenone References Conclusions Acknowledgements • Designed and tested a range of asymmetric Shvo-type catalysts • Good conversions in pressure hydrogenation of acetophenone • Variable conversions under transfer hydrogenation conditions • Modest ees achieved in both pressure and transfer hydrogenation • Complexes also indicate good activities for reductions of imines • Good general route to the synthesis of a library of a new class of asymmetric ruthenium complexes 1) M. Wills, D. S. Matharu and J. E. D. Martins, Chemistry; An Asian Journal, 2008, 3, 1374-13832) J. E. D. Martins, D. J. Morris, B. Tripathi and M. Wills, J. Organomet. Chem., 2008, 693, 3527-35323) J. E. D. Martins, G. J. Clarkson and M. Wills, Org. Lett. 2009, 11, 847-850 4) A. M. Hayes, D. J. Morris, G. J. Clarkson and M. Wills, J. Am. Chem. Soc. 2005, 127, 7318-9 5) D. J. Morris, A. M. Hayes and M. Wills, J. Org. Chem., 2006, 71, 7035-7044 6) N. Menashe, E. Salant and Y. Shvo, J. Organomet. Chem., 1996, 514, 97-102 7) B. L. Conley, M. K. Pennington-Boggio, E. Boz and T. J. Williams, Chem. Rev., 2010, 110, 2294–2312 8) Y. Yamamoto, Y. Miyabe and K. Itoh, Eur. J. Inorg. Chem, 2004, 3651-3661 9) Y. Yamamoto, K. Yamashita and M. Nakamura, Organometallics, 2010, 29, 1472-1478 I would like to thank EPSRC for their generous financial support for this project, the University of Warwick for their excellent facilities, Martin Wills for excellent guidance and supervision throughout and, Guy Clarkson for x-ray crystallography.