1Noyori: BINAP-Ru(II)Cl2BINAP-Ru diacetate catalystThe history ofenantioselectivehydrogenationP. Wipf13/1/20062Chiral environment of the (R)-BINAP-transition metal complexAccess to enantiomerically pure BINAPP. Wipf23/1/20063Asymmetric hydrogenation of ketones by BINAP–rutheniumcomplexesHalogen-containing BINAP–Ru(II) complexes are efficient catalysts for theasymmetric hydrogenation of a range of functionalized ketones.Coordinative nitrogen, oxygen, and halogen atoms near C=O functions direct thereactivity and stereochemical outcome in an absolute sense.(S)-BINAP–Ru(II)catalystAsymmetric hydrogenation of ketones by BINAP–rutheniumcomplexesP. Wipf33/1/20064Asymmetric hydrogenation of β-keto estersArmstrong, J. D.; Keller, J. L.; Lynch, J.; Liu, T.; Hartner, F. W.; Ohtake, N.; Ikada,S.; Imai, Y.; Okamoto, O.; Ushijima, R.; Nakagawa, S.; Volante, R. P. TetrahedronLett. 1997, 38, 3203.Ali, S. M.; Georg, G. I. Tetrahedron Lett. 1997, 38, 1703.P. Wipf43/1/20065Asymmetric hydrogenation of racemic β-keto esters via dynamic kinetic resolutionAsymmetric hydrogenation via dynamic kinetic resolutionStereoselective synthesisof carbapenem antibiotics.(Takasago Co.)Asymmetric hydrogenation via dynamic kinetic resolutionP. Wipf53/1/20066Fine-tuned reactivity and stereoselectivity is a factor of the steric (bulkiness andchirality) and electronic properties of the auxiliaries.Diamine-free BINAP–Ru complexes are totally ineffective.Asymmetric hydrogenation of simple ketones byBINAP/diamine–ruthenium complexesAsymmetric synthesis of various important pharmaceuticalsAsymmetric hydrogenation of simple ketones byBINAP/diamine–ruthenium complexesP. Wipf63/1/20067Excellent enantioselectivity (90-100% ee).Wide scope of substrates (C=O, C=C, C=N).Rivals or exceeds enzymes: e.g. 2,400,000(TON), 228,000 h-1, 63 s-1 (TOF).Development of pharmaceuticals and syntheticintermediates.Successful industrial applications.An enormous scientific or technological impactand even more general social benefits.Significance of BINAP ChemistryAsymmetric transfer hydrogenation catalyzed by RuH[(S,S)-YCH(C6H5)CH(C6H5)NH2](η6-arene)R = alkyl or D; Y = O or NTsNewer developmentsP. Wipf73/1/20068Matsumura, K.; Hashiguchi, S.; Ikariya, T.; Noyori, R., "Asymmetric transferhydrogenation of α,β-acetylenic ketones." J. Am. Chem. Soc. 1997, 119, 8737.The use of chiral Ru(II) catalysts and 2-propanol as the hydrogen donor allowshighly selective reduction of structurally diverse acetylenic ketones to propargylicalcohols with ee’s approaching 99%. The 16-electron complexes 3 are preparedfrom the 18-electron precursors 4 by treatment with KOH. Less than 1% of catalystis necessary. A Ru-H is the reactive species, and catalyst deactivation occurs byaddition of Ru-H across the triple bond.3. HydrogenationsArene Hydrogenations: Hiscox, W. C.;Matteson, D. S. J. Org. Chem. 1996, 61, 8315.Lindlar Hydrogenation: Taylor, R. E.; Ameriks, M. K.; LaMarche, M. J. Tetrahedron Lett. 1997,38, 2057.P. Wipf83/1/20069Lindlar Hydrogenation: Wipf, P.; Venkatraman, S. J. Org. Chem. 1996, 61, 6517.Wipf, P.; Graham, T. H., "Total synthesis of (-)-disorazole C1." J. Am. Chem. Soc. 2004, 126,15346-15347.Asymmetric Hydrogenation with the DuPhos Catalyst: Hoerrner, R. S.; Askin, D.;Volante, R. P.; Reider, P. J. Tetrahedron Lett. 1998, 39, 3455. cf. Burk, M. J. et al. J.Am. Chem. Soc. 1995, 117, 9375.P. Wipf93/1/200610Hayashi Asymmetric Hydrogenation: Schmid, R. et al. Chimia 1997, 51, 303. Pilotplant-scale synthesis of POSICOR®, a new type of calcium antagonist for treatmentof hypertension and angina pectoris.Diimide Reductions: Heathcock, C. H.; Brown, R. C. D.; Norman, T. C., "Synthesisof petrosins C and D." J. Org. Chem. 1998, 63, 5013-5030. Raney-Ni hydrogenationwas slow, unreliable, and relatively low-yielding.White, J. D.; Kim, T.-S.; Nambu, M., "Absolute configuration and total synthesis of (+)-curacinA, an antiproliferative agent from the cyanobacterium Lyngbia majuscula." J. Am. Chem. Soc.1997, 119, 103.Dirat, O.; Kouklovsky, C.; Langlois, Y., "Oxazoline N-oxide-mediated [2+3] cycloadditions:Application to a total synthesis of the hypocholesterolemic agent 1233A." J. Org. Chem. 1998,63, 6634-6642. The use of KO2CN=NCO2K led to overreduction.P.
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