The Noyori Asymmetric Hydrogenation Reaction

The Noyori Asymmetric Hydrogenation Reaction - Myers...

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Chem 2 15 The Noyori Asymmetric Hydrogenation Reaction Myers Reviews : Ager, D. J.; Laneman, S. A. Tetrahedron: Asymmetry 1997 , 8 , 3327–3355. Noyori, R. Acta. Chem. Scand. 1996 , 50 , 380–390. Genet, J. P. In Reductions in Organic Synthesis , Abdel-Magid, A. F., Ed.; ACS Symposium Series, 641; American Chemical Society: Washington, D.C., 1996 , pp. 31–51. Noyori, R. Asymmetric Catalysis in Organic Synthesis ; John Wiley & Sons: New York, 1993 , pp. 56–82. Original Report: O CH 3 OCH 3 O OH CH 3 OCH 3 O H 2 (100 atm) RuCl 2 [( R )-BINAP] (0.05 mol %) CH 3 OH, 36 h, 100 °C 96%, >99% ee Noyori, R., Okhuma, T.; Kitamura, M.; Takaya, H.; Sayo, N.; Kumobayashi, H.; Akuragawa, S. J. Am. Chem. Soc. 1987 , 109 , 5856–5858. Mechanism: PPh 2 PPh 2 OH OH ( S )-(–)-BINAP (±)-1,1'-Bi-2-naphthol ( R )-(+)-BINAP 20% 20% PPh 2 PPh 2 Takaya, H.; Akutagawa, S.; Noyori, R. Org. Synth. 1989 , 67 , 20–32. [( R )-BINAP]RuHCl(CH 3 OH) 2 O O CH 3 OCH 3 [( R )-BINAP]HClRu O O CH 3 OCH 3 [( R )-BINAP](CH 3 OH)ClRu [( R )-BINAP]RuCl(CH 3 O)(CH 3 OH) 2 OCH 3 CH 3 O HO 2 CH 3 OH H 2 CH 3 OH 2 CH 3 OH CH 3 OH • Catalytic cycle: 1/n {[( R )-BINAP]RuCl 2 } n [( R )-BINAP]RuCl 2 (CH 3 OH) 2 CH 3 OCH 3 O O 2 CH 3 OH H 2 HCl Noyori, R. Asymmetric Catalysis in Organic Synthesis ; John Wiley & Sons: New York, 1993 , pp. 56–82. Andrew Haidle • Both enantiomers of BINAP are commercially available. Alternatively, both enantiomers can be + prepared from the relatively inexpensive (±)-1,1'-bi-2-naphthol. Noyori, R.; Tokunaga, M.; Kitamura, M. Bull. Chem. Soc. Jpn. 1995 , 68 , 36–56. CH 3 O O OCH 3 CH 3 CH 3 CH 3 OH O OCH 3 CH 3 CH 3 H 2 (100 atm) CH 3 OH, 23 °C RuCl 2 [( R )-BINAP]–Ru 99%, 96% ee • Evidence that the reduction proceeds through the keto form of the β -keto ester is the fact that the reduction of methyl 2,2-dimethyl-3-oxobutanoate occurs with high yield and high enantioselectivity. However, pathways that involve hydrogenation of the enol form of other β -keto esters cannot be ruled out. Noyori, R.; Takaya, H. Acc. Chem. Res. 1990 , 23 , 345–350.
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Ru Cl H O O P P OCH 3 CH 3 Ru Cl H O O P P CH 3 CH 3 O CH 3 OCH 3 O OH CH 3 OCH 3 O OH ( R ) β -hydroxy ester ( S ) β -hydroxy ester • Of the two possible diastereomeric transition states for complexes with ( R )-BINAP shown below, the one leading to the ( R ) β -hydroxy ester allows the approach of the ketone at an unhindered quadrant (as represented by the light lower left quadrant of the circle). ( R )-BINAP ( R )-BINAP Noyori, R.; Tokunaga, M.; Kitamura, M. Bull. Chem. Soc. Jpn. 1995 , 68 , 36–56. Reaction Conditions: • Noyori has published conditions to prepare the active Ru-BINAP catalyst in one step from commercially available [RuCl 2 (benzene)] 2 , and it can be used without a purification step. Also, the reaction can be run at 4 atm/100 °C or 100 atm/23 °C. Kitamura, M.; Tokunaga, M.; Okhuma, T; Noyori, R. Org. Synth. 1993 , 71 , 1–13. Andrew Haidle P Ru P • A crystal structure of Ru(OCOCH 3 ) 2 [( S )-BINAP] revealed that the rigid BINAP backbone forces the phenyl rings attached to phosphorous to adopt the conformation depicted here (the napthyl rings are omitted for clarity).
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