ASYMMETRIC HYDROGENATION OF KETONES O OH chiral Ru cat H 2 R - - PowerPoint PPT Presentation

Ohkuma, Noyori, 1995, 1998 RuCl2(binap)(chiral diamine) + base

ASYMMETRIC HYDROGENATION OF KETONES

Ru N N H H Ru N N H2 Ru N N H H Ru–amide complex H H H Ru–amine complex R R' O H2 chiral Ru cat A key step of H2 activation R R' OH * Cp*RuCl(cod) + chiral diamine + base Ito, Hirakawa, Ikariya, 1998 chiral Ru cat: ■ ■

EFFECT OF LIGAND STRUCTURES ON ACTIVITY

N NH2 NH2 Ph2P amine conv, %a 6 37 NH2 (CH3)2N NH2 CH3HN NH2 H2N NH2 NH2 CH3O 41 100 2 amine conv, %a none <1 3 98 amine conv, %a 57 OH (CH3)2N N(CH3)2 (CH3)2N NHCH3 (CH3)2N NHTs (CH3)2N

a Determined by 1H NMR.

acetophenone:Ru:diamine:KOH = 100:1:1:1 PH2 = 1 atm, 30 °C,1 h, Conditions: 2-propanol

CATALYST PRECURSOR FOR THE HYDROGENATION

C6H5 O C6H5 OH 2-propanol H2 + Ru cat 10 atm ketone:Ru:diamine = 1000:1:1 (CH3)2N(CH2)2NH2 30 °C, 2 h Ru cat: Ru Ru O O TOF = 100 TOF = product mol/cat mol·h H3C CH3

SOLVENT EFFECT ON THE TURNOVER NUMBERS

solvent 2-propanol TONa ethanol 300 200 methanol 70 THF CH2Cl2 DMF 65 70 CH3CN 30 hexane tert-butyl alcohol 20

aTON = product mol/cat mol

Ru cat 0.2 mol%, H2 10 atm, 30 °C, 2 h Conditions: Ru cat = (Cp*RuOCH3)2 + (CH3)2N(CH2)2NH2

solvent H2 or D2 + Cp*RuCl(cod) (CH3)2N(CH2)2NH2 KOH 1 atm

ISOTOPE LABELING EXPERIMENTS

30 °C, 2–3 h OD OH D OH H2 D2 D2 7 90 ketone:Ru:diamine:KOH = 100:1:1:1 H2 or D2 solvent D content, %a

a Determined by 1H NMR and D NMR.

~100% yield C6H5 O C6H5 OH H (D)

OH C6H5 N Ru H NH C H O C6H5

A POSSIBLE MECHANISM

Ru HN N Ru H H2N N N Ru HN H H N Ru N H H O C6H5 H R O H Cp*RuCl(cod) KOH (Cp*RuOCH3)2 (CH3)2N(CH2)2NH2 (CH3)2N(CH2)2NH2 + + + H2 ROH ROH

ASYMMETRIC HYDROGENATION WITH CHIRAL Ru CATALYSTS

C6H5 OH 72% ee (R) C6H5 OH C6H5 OH C6H5 OH C6H5 OH C6H5 OH 79% ee (R) 79% ee (R) 73% ee (R) 88% ee (R) 81% ee (R) C6H5 R O C6H5 R OH 30 °C, 6–18 h H2 + KOH 10 atm ketone:Ru:diamine:KOH = 100:1:1:1 Cp*RuCl(cod) chiral diamine 2-propanol NH2 N C2H5 chiral diamine

S R

examples:

EFFECT OF STRUCTURES OF DIAMINES ON THE ee VALUES

NH2 N C2H5 N H NH2 N H N(CH3)2 N H N N H N CH3 3% ee (R) 72% ee (R) 13% ee (S) 40% ee (S) 13% ee (R)

ENANTIO–FACE SELECTION OF KETONE

N N Ru H H H O R OH Ar R H

R

catalyst precursor

R

Ar

S

possible transition state