Ruthenium (BINAP)(Diamine) Catalysts for Asymmetric Hydrogenation of Aryl Ketones

June 20, 2026 Metal Catalysis, Science ruthenium, BINAP, diamine, aryl ketone, asymmetric hydrogenation, DPEN, DAIPEN, Noyori, chiral

While first-generation (BINAP)RuCl₂ catalysts excel at β-keto esters, they give poor enantioselectivity on unfunctionalized aryl ketones. Noyori’s breakthrough was the introduction of a chiral 1,2-diamine co-ligand — DPEN (1,2-diphenylethylenediamine), DAIPEN, or trans-DACH — to create the (BINAP)(diamine)Ru(II) system. This combination reduces simple aryl ketones to chiral alcohols with >99% ee through the metal–ligand bifunctional mechanism.

The Bifunctional Mechanism

The active catalyst has both a Ru–H hydride and an N–H proton on the diamine. In the transition state, the hydride is delivered to the carbonyl carbon while the N–H proton transfers to the oxygen — a concerted [2+2] addition that does not require substrate coordination to the metal. This outer-sphere pathway explains:

  • Broad substrate scope — works on ketones that poison inner-sphere catalysts.
  • High tolerance — compatible with halogens, heterocycles, and sulfur.
  • Mild conditions — typically 1–10 bar H₂ at room temperature.

Diamine Co-Ligand Choice

The diamine is as important as the bisphosphine for selectivity:

  • (S,S)-DPEN — the standard; works with (S)-BINAP for predictable induction.
  • (S,S)-DAIPEN — superior for sterically hindered and α-branched ketones.
  • (S,S)-TsDPEN — also enables transfer hydrogenation (ATH) in isopropanol or formate/water without H₂.
  • trans-DACH — cyclohexanediamine; cost-effective alternative for scale-up.

Substrate Classes

  1. Aryl methyl ketones — acetophenone-type, >99% ee.
  2. Aryl alkyl ketones — propiophenone, butyrophenone.
  3. α-Substituted ketones — generates adjacent stereocenters.
  4. Heteroaryl ketones — 2-acetylpyridine, acetylfuran.
  5. α,β-Unsaturated ketones — selective 1,2-reduction.

Operational Notes

The precatalyst [(BINAP)RuCl₂]₂ dimer is cleaved in situ by the diamine and base (typically KOtBu) under H₂. Loadings of 0.01–0.5 mol% are standard. For transfer hydrogenation (no H₂), the preformed [(TsDPEN)Ru(p-cymene)Cl₂] precatalyst is preferred.

Industrial Relevance

The (BINAP)(diamine)Ru system is deployed in the manufacture of antibiotics, fragrance alcohols, and chiral intermediates for multiple approved drugs. Its predictability — both enantiomers accessible by ligand choice — and documented regulatory history make it the default for any new aryl ketone hydrogenation campaign.

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