Asymmetric Catalysis using DPEN and Proline Derivatives

1. Asymmetric catalysis using DPEN and proline derivatives Charles V. Manvillea, Martin Willsa, Gordon Docherty,b Ranbir Paddab and Gary Woodwoodb. a: Department of Chemistry, University of Warwick, Coventry, CV4 7AL b: Rhodia Consumer Specialities Ltd, PO Box 80, Trinity Street, Warley, Oldbury, B69 4LN Introduction: Amines have been used in catalysts since 1902, when pyridine was used by Dobner in a modification of the Knoevenagel Condensation.1 The first use of a chiral amine in catalysis was the use of proline in the Haios-Parrish-Eder-Sauer-Wiechert reaction in the 1970s.2 Since then proline and it’s derivatives have been used as organocatalysts in a number of reactions, including conjugate additions to nitrostyrenes,3 Diels-Alder reactions4 and aldol reactions.5 These reactions can be performed with good activity and selectivity with moderate catalyst loadings. DPEN is often used as a chiral ligand in metal centred catalysts, most famously in the system reported by Noyori.6 Derivatives of DPEN are used in the Wills group to form tethered catalysts for asymmetric reductions of ketones and imines where it acts to both impart chirality to the catalyst and act as a hydrogen source in the reduction step.7 Recently, DPEN derivatives have been investigated for use as organocatalysts. One of the more successful results has been for the Michael addition of ketones to nitrostyrenes.8,9 Reactions were also run using Rh(Cp*) and Ir(Cp*) as the metal centres. These catalysts gave much lower conversions and e.e.s for all of the tested ketones, than the corresponding Ru(p-cymene) catalyst. a. Determined by G.C. b. Determined by comparison of G.C. and optical rotation with literature data. Azo Coupling It has been shown that derivatives of DPEN and proline, containing a diphenyl phophinamide group, can catalyse the addition of acetone to nitrostyrenes, but is unsuccessful when using other aldehydes.9 It was attempted to improve the scope of the catalyst by coupling the PODPEN to proline. These catalysts proved to be unreactive in the Michael addition, but were able to catalyst the coupling of DEAD to aldehydes. Derivatives using TsDPEN were also made and tested The use of an iridium metal centre changes the major determination of product chirality from the proline part of the ligand to the DPEN part of the ligand a. Determined by G.C. b. Determined by comparison of G.C. and optical rotation with literature data. New catalyst synthesised by coupling proline and a DPEN derivative. R = Ph2P(O), Ts. Further ligands were synthesised by coupling two Boc-(S)-prolines to a central DPEN unit, using the same conditions as for the coupling of Boc-(S)-proline to TsDPEN. 1 (R,R) (R,R) 5 2 (S,S) 6 (S,S) a: N-Boc-(S)-proline, ethyl chloroformate, Et3N, THF. b: 20%Me2S-DCM, triisopropylsilane, TFA, 0 °C. 3 (R,R) When these new ligands were tested, using the same conditions used for ligands 3 and 4, in the transfer hydrogenation of ketones, they proved to be faster than the TsDPEN ligands, but had a lower selectivity for linear ketones. However, the hydrogenation of cyclic indanone and tetralone like ketones gave good to high e.e.s in all of the tested ketones when using ligand 6. 4 (S,S) a: N-Boc-(S)-proline, ethyl chloroformate, Et3N, THF. b: 20%Me2S-DCM, triisopropylsilane, TFA, 0 °C.c: Formic acid, 0 °C Catalyst loading; 1 mol%. a. Determined by G.C. b. Determined by G.C. unless shown. c. Determined by comparison of G.C. and optical rotation with literature data. d. 2 mol% catalyst used. e. Determined by HPLC Asymmetric Transfer Hydrogenation Derivatives of both DPEN6,7 and proline10 have been used as ligands for the asymmetric transfer hydrogenation of ketones using metal centres. The Ts-DPEN derivatives were tested as ligands, and were found to be successful when used with a ruthenium p-cymene metal centre in water, using sodium formate as the hydrogen donor, at a catalyst loading of 1 mol%. For the cyclic ketones the ligand formed from the coupling of two (S)-prolines to (S,S)-DPEN (6) proves to form a faster and more selective catalyst for all of the tested substrates than the (S)-proline / (R,R)-DPEN ligand (5). Catalyst loading; 1 mol%. a. Determined by G.C. b. Determined by comparison of G.C. and optical rotation with literature data. c. [RhCl2(Cp*)]2 used instead of [RuCl2(p-cymene)]2 Acknowledgements: I would like to thank Martin and the Wills group for their support and encouragement during this project. I would also like to thank my industrial supervisors Gary Woodwood and Gordon Docherty and the EPSRC and Rhodia for financial support. Catalyst loading; 1 mol%. a. Determined by G.C. b. Determined by comparison of G.C. and optical rotation with literature data. References: 1 O. Doebner. Berichte der deutschen chemischen Gesellschaft, 1902, 35, 1136-1147 2 Z. G. Hajos, D. R. Parrish. J. Org. Chem. 1974, 39, 1615-1621; U. Eder, G. Sauer and R. Wiechert, Angew. Chem. Int. Ed. 1971, 10, 496-497. 3 B. List, P. Pojarliev and H. J. Martin. Org. Lett.2001, 3, 2423; J.M. Betancort, K. Sakthivel, R. Thayumanavan, C.F. Barbas III. Tetrahedron Lett.2001,42, 4441 4 H. Sundén, R. Rios, Y. Xu, L. Eriksson and A. Córdova. Adv. Synth. Catal. 2007, 349, 2549-2555 5 Q. Gu, X-F. Wang, L. Wang, X-Y. Wu and Q-L. Zhou. Tetrahedron Asymmetry, 2006, 17, 1537-1540 6 H. Doucet, T. Ohkuma, K. Murata, T. Yokozawa, M. Kozawa, F. Katayama, A.F. England, T. Ikariya and R. Noyori. Angew. Chem. Int. Ed.1998, 37, 1703-1707 7 For recent work see: J.E.D. Martins, G.J. Clarkson and M. Wills, Org Lett, 2009, 11, 847-850; J.E.D. Martins, D.J. Morris and M. Wills, Tetrahedron Lett. 2009, 50, 688-692 S. B. Tsogeova and S. Wei, Chem. Commun. 2006, 1451-53 D. J. Morris, A. S. Partridge, C. V. Manville, D.T. Racys, G. Woodward, G. Docherty and M. Wills, Tetrahedron Lett. 2010, 51, 209-212 For recent work see: Z. Zhou, L. Wu, Catalysis Communications, 2008, 9, 2539-2542; J. Mao and J. Guo, Chirality, 2010, 22, 173-181 These results show that for a ruthenium centre the selectivity of the catalysts is mainly determined by the proline portion of the ligand, with the most selective catalyst being the one using (S)-proline coupled to (R,R)-TsDPEN as the ligand (3). The (S)-proline / (S,S)-TsDPEN ligand (4) forms a faster catalyst in most cases Catalyst loading; 1 mol%. a. Determined by G.C. b. Determined by comparison of G.C. and optical rotation with literature data.