定义Definition
野依不对称氢化是用手性 BINAP-钌（或 BINAP/二胺-钌）催化剂，以氢气对酮、β-酮酸酯和官能化烯烃进行高对映选择性加氢，得到手性醇等产物的反应。
The Noyori asymmetric hydrogenation uses chiral BINAP–ruthenium (or BINAP/diamine–ruthenium) catalysts and hydrogen to reduce ketones, β-keto esters and functionalised alkenes with high enantioselectivity, giving chiral alcohols and related products.
催化剂Catalysts
BINAP 是轴手性的双膦配体（联萘），形成刚性 C₂ 对称手性环境。BINAP-Ru(II) 二羧酸盐还原 β-酮酸酯；1995 年发展的 RuCl₂(BINAP)(二胺) 加碱后可还原简单芳香酮，转换数可达 10⁵ 以上。
BINAP is an axially chiral binaphthyl bisphosphine that creates a rigid C₂-symmetric environment. BINAP–Ru(II) dicarboxylates reduce β-keto esters; RuCl₂(BINAP)(diamine) with base (1995) reduces simple aryl ketones with turnover numbers above 10⁵.
机理Mechanism
二胺型催化剂按“金属–配体双功能”机理工作：Ru–H 的氢负离子与 N–H 的质子经六元环过渡态同时转移给羰基 C=O，底物无需与金属直接配位（外层机理）。
Diamine catalysts operate by metal–ligand bifunctional catalysis: the Ru–H hydride and an N–H proton are delivered simultaneously to C=O through a six-membered transition state, without the substrate binding the metal (outer-sphere mechanism).
意义Significance
野依良治因不对称氢化与诺尔斯共获 2001 年诺贝尔化学奖。该技术工业化用于生产（−）-薄荷醇前体、抗生素中间体、左氧氟沙星中间体等。
Ryōji Noyori shared the 2001 Nobel Prize in Chemistry with Knowles for asymmetric hydrogenation. The technology is used industrially for menthol precursors, antibiotic intermediates and levofloxacin intermediates.
反应Reactions
0.001–1 mol% 催化剂，异丙醇，KOtBu，1–50 atm H₂，室温
0.001–1 mol % catalyst in 2-propanol with KOtBu, 1–50 atm H₂, room temperature
预催化剂在碱作用下生成 Ru–H/N–H 活性物种。
Base converts the precatalyst into the Ru–H/N–H active species.
氢负离子和质子经六元环过渡态协同转移到 C=O。
Hydride and proton transfer to C=O through a six-membered transition state.
H₂ 异裂再生活性物种。
Heterolytic H₂ cleavage regenerates the active species.
简单芳香酮的还原。
Reduction of a simple aryl ketone.
年表Timeline
- 1980
野依等合成 BINAP
Noyori and co-workers synthesise BINAP
- 1987
BINAP-Ru 氢化 β-酮酸酯
BINAP–Ru hydrogenation of β-keto esters
- 1995
Ru-双膦-二胺催化剂氢化简单酮
Ru–bisphosphine–diamine catalysts for simple ketones
- 2001
野依共获诺贝尔化学奖
Noyori shares the Nobel Prize in Chemistry