Noyori asymmetric hydrogenation template

Simplified Noyori monohydride cycle for methyl acetoacetate: RuHCl[(R)-BINAP] binds the keto ester as an O,O-chelate, hydride transfer to the ketone carbon sets the stereocentre, and H₂ cleaves the Ru–O bond heterolytically to release (R)-methyl 3-hydroxybutanoate; Ru stays Ru(II); key step: hydride transfer from Ru to C=O.

What the template shows

• Ru(II)–BINAP reduces a β-keto ester to one enantiomer of the β-hydroxy ester (simplified monohydride scheme)
• Overall: CH₃COCH₂CO₂CH₃ + H₂ → (R)-CH₃CH(OH)CH₂CO₂CH₃ (cat. RuCl₂[(R)-BINAP], MeOH, ≈100 atm H₂; >99% ee)
• RuHCl[(R)-BINAP]
• Keto ester chelate
• Ru(II), new (R) centre
• no redox: H₂ split
• Noyori (Nobel Prize 2001): RuCl₂[(R)-BINAP] gives (R)-methyl 3-hydroxybutanoate and the (S)-catalyst the (S)-ester, both in >99% ee.
• The ester C=O must chelate Ru with the ketone: simple ketones need the later Ru–diphosphine–diamine catalysts.
• Ru stays Ru(II): H₂ is split heterolytically (H⁻ to Ru, H⁺ to the alkoxide oxygen), not by oxidative addition; HCl (from RuCl₂ + H₂ → RuHCl + HCl) assists.
• With α-substituted β-keto esters the fast racemising α-centre allows dynamic kinetic resolution: one of four stereoisomers in high ee and de.
• Key step: hydride transfer from Ru to the ketone
• Simplified as a four-centre addition: the Ru–H electrons go with H to the ketone carbon and the C=O π electrons form the Ru–O bond. The chelate and the chiral BINAP pocket let hydride reach only one face (here giving (R)).
• methyl acetoacetate
• Cl, (R)-BINAP and solvent ligands are named, not drawn; simplified scheme, so electron counts are not given · every part of this figure is editable

Drawn with 40 atoms, 6 arrows, 51 shapes – every one editable in MolDraw.

Sources

• Clayden, Greeves & Warren, Organic Chemistry, 2nd ed., OUP 2012, ch. 41 Textbook
• Kürti & Czakó, Strategic Applications of Named Reactions in Organic Synthesis, Elsevier 2005, Noyori asymmetric hydrogenation Textbook