Asymmetric ketone and imine reductions using ruthenium cata - PowerPoint Presentation

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Asymmetric ketone and imine reductions using ruthenium catalysts

Jonathan Hopewell, José E. D. Martins and Martin Wills*

1) M. Wills, D. S. Matharu and J. E. D. Martins,

Chemistry; An Asian Journal

,

2008

,

3,

1374-1383

2) 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, 7318-95) 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, 97-1027) B. L. Conley, M. K. Pennington-Boggio, E. Boz and T. J. Williams, Chem. Rev., 2010, 110, 2294–23128) Y. Yamamoto, Y. Miyabe and K. Itoh, Eur. J. Inorg. Chem, 2004, 3651-36619) Y. Yamamoto, K. Yamashita and M. Nakamura, Organometallics, 2010, 29, 1472-1478

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

2

1-5 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

Conclusions

Designed and tested a range of asymmetric Shvo-type catalysts

Good conversions in pressure hydrogenation of acetophenone Variable conversions under transfer hydrogenation conditions

ComplexRR’R’’7PhTBSTMS8PhTBSTIPS9PhTBSPh10PhTIPSTMS11PhTIPSPh12PhTIPSTBS

Hydride

synthesis

Hydrogenation of ketones

Hydrogenation of imines

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

Introduction

Hydrogen sourceiPrOHFA/TEAH2CatalystConv. %ee %Conv.%ee %Conv. %ee %47 N/A53N/A-N/A572 N/A78N/A92N/A626 N/A14N/A11N/A731 <2 (R)11<2 (R)97-814 21 (S)1820 (S)1017 (S)993 4 (R)726 (R)965 (R)1015 10 (R)1212 (R)2710 (R)1176 6 (R)448 (R)948 (R)

Acknowledgements

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.

Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK

J.P.Hopewell@Warwick.ac.uk

Ruthenium catalyst synthesis

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.

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

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

28°C, 22 h, 0.5 mol% catalyst in 5:2 FA/TEA and acetonitrile

Hydrogenation results

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

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

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

References