Atom-Economical and Sustainable C-N Bond Formation Reactions from Alcohols
and N-Sources via Catalytic Hydrogen Transfer Reactions
September 15th, 2015
Past and Present Research Systems of Green Chemistry
Seoul National University, Republic of Korea
Soon H. Hong
Classical Chemical Synthesis
CatalysisSustainable Chemical
Synthesis
The HongSH Group @ SNU
Outline1. Ru Catalyzed Direct Amide & Imide Synthesis from Alcohol and N-Sources
2. Transfer Hydrogenation of Formyl Esters and Cyclic Carbonates: Production of MeOH
R OH +R N
H
O
R'R' C N[Ru]
H O
O
R
O O
ROH CH3OH
OO
O
+
+
H
H
R
HO
R
OH
[Ru], K2CO3
Transfer Hydrogenation
TON up to 16600
TON up to 3240
[Ru], K2CO3
CH3OH
R C N + CH3OHRuH2(CO)(PPh3)2(IiPr)
R NH
H
O
R NH2 + CH3OHRuH2(CO)(PPh3)2(IiPr)
-H2
(No byproduct)
R NH
H
ORu
H
NN
OC PPh3
HPh3P
RuH2(CO)(PPh3)2(IiPr)
3. N-formylation Utilizing Methanol as Sustainable C1 Source
Living Organism Medicine
Amide Bond
Polymer Industry
N
OO
H
N
Organic Synthesis
O
C
N
H
Amide: A Central Functional Group in Nature
Traditional Amide Synthesis
High Atom Economical Amide Synthesis – A Key Green Chemistry Research Area from Pharmaceutical Manufacturers –
(ACS, Green Chemistry Institute Pharmaceutical Roundtable)
Generate huge amount of toxic waste
Green Chem. 2007, 9, 411
Direct Amide Synthesis from Alcohol
R OH
R O[M]H2 +
R NH
R'
O
R NH
O
H NH
R'
O
O NH
O
R'
HN
HN
R'
O
Amide
Formamide
Urea
R'' R'Carbamate
[M]
UnactivatedAmine
Nitrile
Azide
Ammonia
Isocyanate
Imine
Amide
R
OImide
Activated
H
Basic Concept of Our Reaction Development: Alcohol Activation
Acceptorless, External Oxidant- and Base-free Catalytic Cycle
[Ru]
[Ru-H2]
H2
R R' R'
HN
OHRor
R R' R'N
ORor
Adv. Synth. Catal. 2012, 354, 3045
Mechanism study (Ru Hydride)Organometallics 2010, 29, 1374J. Org. Chem. 2010, 75, 3002
Catalyst improvementAdv. Synth. Catal. 2009, 351, 2643Eur. J. Org. Chem. 2010, 4266Organometallics 2010, 29, 1374ACS Catalysis 2014, 4, 2889 (Fe)
Expansion of the scopeJ. Org. Chem. 2011, 76, 10005Angew. Chem. Int. Ed. 2010, 49, 6391Organic Lett. 2012, 14, 4646Organic Lett. 2012, 14, 6028Organic Lett. 2012, 14, 2992J. Am. Chem. Soc. 2013, 135, 11704Organic Lett. 2014, 16, 4404
ReviewsOrg. Biomol. Chem. 2011, 9, 20Synlett 2011, 1481
Dehydrogenative Amide Synthesis from Alcohol
Ru
Cl
ClN
N
Me
Me
+ KOtBu + ROH
N NI-
RuH2(PPh3)3
NaH
Ru
H
NN
OC PPh3
Ph3P H
[Ru]IiPr
Organometaliics 2010(Madsen, Chem. Eur. J. 2010)
Angew. Chem. 2010 J. Am. Chem. Soc. 2013
Amide Synthesis with Complete Atom Economy
Classical Pathway
R' OHoxidant
(e.g. KMnO4)
R CNreductant
(e.g. LiAlH4)
R' OH
O
R NH2
coupling reagents
(e.g. SOCl2, Et3N)R'N
H
O
R
- At least 3 steps required !
- Large amount of chemical waste !
+
- Poor atom economy !
Ruthenium Catalyzed Reaction
R' OHR CN R'NH
O
RAlcoholNitrile
- One Step Pathway from Nitrile to Amide
Amide
- No Side Product at all
+
RuH2(CO)(PPh3)3 (5 mol%)NHC precursor (5 mol%)
- The First 100% Atom Economical Amide Bond Synthesis
NaH (20 mol%)toluene reflux, 48 h
Byungjoon Kang
Direct Amide Synthesis from Nitrile and Alcohol
J. Am. Chem. Soc. 2013, 135, 11704Atom, Step, Redox Economy!
Direct Amide Synthesis from Nitrile and Alcohol
R+ R' OH NH
R CN
RuH2(CO)(PPh3)3 (10 mol%)NHC precursor (10 mol%)
R'
O
Substrate Scope
NN
Cl-
NHC precursorNitrile Alcohol Amide
1.1 equivNaH (20 mol%)
toluene reflux, 48 h
NH
O
> 99 %
NH
O
OMe81 %
NH
O
89 %
NH
O
84 %
NH
O
O
76 %
NH
O
N
73 %
NH
O
53 %F
NH
O
56 %
15NH
O
94 %
NH
O
84 %
NH
O
53 %Cl
15NH
O13C
96 %
J. Am. Chem. Soc. 2013, 135, 11704
Amide Synthesis with Complete Atom Economy
Direct Amide Synthesis from Nitrile and Alcohol
J. Am. Chem. Soc. 2013, 135, 11704(Computational mechanistic study: Z.-X. Wang ACS Catal. 2014, 4, 2854
Mechanism Study
Reaction Profile
Nor amine or aldehyde intermediateis detected.
Catching Intermediate
CNcatalytic system
NH
H+
NH
H
[Ru]
BEt3
Imine capturing reagent
NH
H
BEt3 NH
H
[Ru]
+
A B A'
10.2 ppmJ = 23.5 Hz
9.2 ppmJ = 22.9 Hz
9.0 ppmJ = 21.5 Hz
Unusual protonated imine intermediate was detected in NMR study
[Ru]H2
N
R
H
[Ru]
H
N
R
H
[Ru]
H
R'CH2O H
N
R
H
[Ru]
H
H2O
H
R'
R' NH
O[Ru]H
R
R CN
R'CH2OH
R' NH
O
RN
R
HH + [Ru]
[Ru] = [Ru(NHC)Ln]
Proposed Mechanism
Amide Synthesis with Complete Atom Economy
Sabo-Etienne, J. Am. Chem. Soc. 2010, 132, 7854
Cyclic Imide from Nitrile and Diol
Jaewoon Kim
Traditional Method
HO2CCO2H H2N R1
nN
O
O
R1
– 2H2On
NC R2
R1
R3
R4
CN
R5
+ 2 H2O+
+
cat. IrH5(PiPr3)2
– NH3
HN
R2
R1
R3 R4R5
OO
S. I. Murahashi, Angew. Chem. Int. Ed. 2003, 42, 3302
R1 R2cat. Fe3(CO)12
+ H2N R3N
O
O
R3
R1
R2
M. Beller, Angew. Chem. Int. Ed. 2009, 48, 6041
NH
O
N
+ CO
+ CO
cat. Ru3(CO)12
H2O, ethyleneN
O
O
N
N. Chatani, J. Am. Chem. Soc. 2009, 131, 6898
Cyclic imide from diol and amine
Angew. Chem. Int. Ed. 2010, 49, 6391-6395
R1 CN +HO
HON
O
O
R1
- 2H2
R2
R3
R2
R3
Organic Lett. 2014, 16, 4404-4407
Cyclic imide from diol and nitrile
N
O
OPh OMe
N
O
OOMe
N
O
OOMe
78% 80% 51%
N
O
O
Ph
81 %
N
O
O
86 %
N
O
O
70 %
N
O
O
R4
R3 NH2OH
OHR1
R2
R1
R2
R4
R35 mol % , 20 mol % NaH
5 mol % CH3CN, toluene reflux
N NI-
+5 mol % RuH2(PPh3)3
5 mol % , 20 mol % NaHbenzene reflux
N NI-
5 mol % RuH2(PPh3)3
- 4H2
CO2 Conversion
Combustion Reaction
Condenser & dry column
Exhaust gas O2, N2 CO2
+ CO2
NR2
NR2 C
OH
OH
R1R1
Amine (aq) solution
Carbamate (aq) solution
- CO2
CO2 Capture & Utilization Strategy
Seunghyo Kim
Same reaction efficiency with commercial >99.999% CO2 gas
Angew. Chem. Int. Ed. 2014, 53, 771-774.
Yield
amine solution = amine/water (7 m)
Ph H
AgI (2 mol %)
COH
OHCl
CO2 Ph
Cs2CO3 (1.5 eq)
DMF, 16 h, 25 oC
Amine Solvent Volume
Pure CO2 (>99.999%)
NH2HO
HN
HO OH
NHO OH
HN
OH OH
OHH2N
HN NH
YieldAmine Solvent Volume
H2O
H2O
H2O
H2O
DMF
H2O
DMF
H2O
DMF
H2O
DMF
H2O
DMF
H2O
25 mL
10 mL
5 mL
2.5 mL
5 mL
5 mL
5 mL
5 mL
5 mL
5 mL
82%
77%
67%
38%
73%
83%
64%
73%
59%
8%
67%
19%
NR
69%
69%
amine solution = amine/water (7 m)
CO2
125 oC
25 oC
HNN
R2 COH
O
R1
R2
R1
(1 mmol)
C
O
OH
O
COH
O
COH
O
O
COH
O
HO
C
O
OH
COH
O
COH
O
C
O
OH
C
O
OH
CO2 from combustion
125 oC
25 oC
NH2HO
HN
HO COH
O
CO2
R H
AgI (2 mol %)
COH
OHClCs2CO3 (1.5 eq)
DMF, 16 h, 25 oC
CO2 Source
Directly from exhaust gas
99.999% CO2
Captured from exhaust gas by MEA
Dry ice
55 times recycled MEA
Yield
No reaction
39%
83%
82%
80%
MEA solution = ethanolamine/H2O (7 m)
C
O
OH
R
84%
80%
88%
81%
85%
90%
89% 67% 65%
Cl
COH
O
HexylC
O
OH
COH
O
R MgBrHCl
RC
OH
OTHF, 25 oC, 1 h
CO2 from combustion
125 oC
25 oC
NH2HO
HN
HO COH
O
CO2
99%
89%
98%
OC
O
O
Ph
OC
O
O
nBu
OC
O
O
Ph
OC
O
O
Cl
Cl
O
R
OC
O
O
K2CO3 ( 2 mol %) , ZnBr2 ( 2 mol %)
N N
( 2 mol %)
CO2 from combustion
125 oC
25 oC
NH2HO
HN
HO COH
O
CO2R
90%
91%93%
92%
DMSO, 24 h, 80 oC
Angew. Chem. Int. Ed. 2014, 53, 771-774.
CO2(aq) CH3OH(aq) H2O(l)3 H2(aq)+
G-79 (kJ/mol), H -106 (kJ/mol)
+
The Highest Oxidation State of Carbon
> Thermodynamically Stable
Eco-friendly Methanol Production
Methanol
Carbon Dioxide
- Greenhouse gas
Hydrogen Transfer
- Renewable
- Nontoxic - Nonflammable
- Inexpensive
Homogeneous Catalyst
CO2
Ru(acac)3, Triphos3 H2 CH3OH H2O
H
O
OH H
O
OR
Sc(OTf)3, ROH
-H2O
a) (TON 2.5)
(TON ~221)b)Sanford
Leitner
HNTf2
Ru
Cl
PMe3Me3PPMe3
OAcMe3P
a)
N
N
P(tBu3)2
RuCO
H
b)
Ph2P
Ph2P
PPh2
Triphos
Sanford, J. Am. Chem. Soc. 2011, 133, 18122
Leitner, Angew. Chem. Int. Ed. 2012, 51, 7499
- High selectivity
- Rational tuning of the reactivity
- Mild reaction condition
Advantages of homogeneous catalyst
CO2 H2+H
CO
O2 MeOH
H2 (10 ~ 50 bar)
MeOHN
N
P(tBu3)2
RuCO
H
CO2O
OC
O HOOH
O
H2 (50 bar)MeOH
HN
PPh2
PPh2
RuCO
H
Cl
Milstein, Nature Chem. 2011, 3, 609
Ding, Angew. Chem. Int. Ed. 2012, 51, 13041
[Ru]
[Ru], KOtBu+
- H2O
Indirect Way to Produce Methanol
R H
O
R R
O
R OR
O
R NR2
O
RO OR
O
RO NR2
O
aldehyde ketone ester carboxamide carbonate carbamate
less electrophilic carbonyl group
There are no reports of TH with these compounds
OH
Hydrogen source
Transfer hydrogenation (TH) :2-propanol is used as both solvent and hydrogen source
Hydrogenation : High pressure of H2 gas is used
Indirect Way to Produce Methanol
Seunghyo Kim
H O
O
H O
O
H O
OH O
O
H O
O
OO
O
OO
O
OO
O
nBu
OO
O
Ph
OO
O
>99% 94%>99% >99% 34%
>99%91% >99% 93% >99%
H O
O
R
OO
ROH CH3OH
CH3OHOO
O
+
+
H
H
HO
R
OH
[Ru], K2CO3
transfer hydrogenation
TON up to 16600
TON up to 3240
[Ru], K2CO3
Ru CON
PR2
P
H
H
Ph2Cl
[Ru]
O O
O
6%
H O
O
OH
81%
reduced
ACS Catalysis 2014, 4, 3630-3636.
The first transfer hydrogenation of cyclic carbonates and formyl esters.
N-Formamide Synthesis from Nitrile & Amine:Using Methanol as C1 Source
Byungjoon Kang
CO
H
H
HH
Methanol
◦ One of the most abundant chemical on earth (> 100 Mtonne/year).
◦ Harmless, renewable, and environmentally benign.
◦ Easily handled in laboratory scale. (O2 and moisture stability)
◦ Can be synthesized by environmental friendly method.
Methanol : Promising C1 source
Classical C1 Feedstock
CH3I CH3MgBr
H CCl3
O
Cl Cl
O
...
IdealAlternative
◦ Thermodynamic huddle of methanol utiliza-tion
CH3OHcatalyst
H2
CH2O + Coupling partner Product
Key step!
General Scheme for Methanol Utilization
CH3OH + H2CH2OMethanol Formaldehyde
H = 84 kJ/mol
CH3CH2OH + H2CH3CHO
Ethanol Acetaldehyde
H = 68 kJ/mol
+ H2
Benzyl alcohol
H = 54 kJ/molPh OH Ph OBenzaldehyde
Methanol utilization is relatively unexplored compare to normal alcohol !
N-Formamide Synthesis from Nitrile & Amine:Using Methanol as C1 Source
Methanol : Promising C1 source
◦ C-C Bond Formation
[Ir] (5 mol%)toluene 80 C
24 h
PMBO
CH3OH+
PMBO
OH
67 %
IrP
P
O
O
NO2
Cl
P-P = DPPF
[Ir]
M. J. Krische, Nature Chem. 2011, 3, 287
[{Cp*RhCl2}2] (7.5%)Cs2CO3 (5 equiv), O2
CH3OH+
T. J. Donohoe, Angew. Chem. Int. Ed. 2014, 53, 761
R
O
R'65 C, 24 h R
O
R'
[{Cp*IrCl2}2] (0.2%)KOtBu (1 equiv)
CH3OH+
Feng Li, Chem. Eur. J. 2013, 19, 14030
150 CNH HN NH
◦ C-N Bond Formation
N-methylation
CH3OH+
Feng Li, RSC Adv. 2012, 2, 8645
SNH2
O O[Cp*IrCl2] (0.1%)NaOH (1 equiv)
150 C
SNH
O O
N-formylation
CH3OH+
F. Glorius, Org. Lett. 2013, 15, 1776
NH2
Ru(cod)(2-methylallyl)2ICy·HCl, KOtBu, styrene N
Htoluene, 120 C, 24 h(- ethylbenzene)
H
O
CH3OH+
N. Asao, Chem. Eur. J. 2013, 19, 11832
NH2AuNPore cat, O2 N
H120 C, 20-72 h(- H2O)
H
O
: Stoichiometric amount of activating reagent required !
Long reaction time !
N-Formamide Synthesis from Nitrile & Amine:Using Methanol as C1 Source
N-Formamide synthesis using methanol
R C N + CH3OHRuH2(CO)(PPh3)2(IiPr)
R NH
H
O
R NH2 + CH3OHRuH2(CO)(PPh3)2(IiPr)
-H2
(No byproduct)
R NH
H
ORu
H
NN
OC PPh3
HPh3P
RuH2(CO)(PPh3)2(IiPr)
◦ No base. No hydrogen acceptor. No stoichiometric oxidant.
◦ High redox- and step-economy.
N
HN
N
HN NH2
OH
HN
HN
O
HO
O
HO O Leucovorin
OHHNHN
OH
HO O
Formoterol
OO
O
OHN
O
H10
3
Orlistat
N-Formamide : versatile functional group with high bio-activity
N-Formamide Synthesis from Nitrile & Amine:Using Methanol as C1 Source
N-Formamide synthesis using methanol
R C N + CH3OHRuH2(CO)(PPh3)2(IiPr) (10%)
R NH
H
O
Benzene, 90 C, 3 - 10 h12 - 20 equiv.
R NH2 + CH3OHRuH2(CO)(PPh3)2(IiPr) (10%)
R NH
H
O
Toluene, 110 C, 24 h- H220 equiv.
NH
H
O
87 %
NH
H
O
91 %
MeO
NH
H
O
Cl
89 %
NH
H
O
73 %
NH
H
O
74 %
NH
H
O
72 %
NH
H
O
68 %
NH
H
O
71 %
NH
H
O
60 %
O
HN H
O
82 %
N H
O
87 %
NH
H
O
O
66 %
N H
O
88 %
N
NH
H
O
71 %
NH
O
H
95 %
ONH
H
O
80 %
NH
H
O
95 %MeO
N-Formamide Synthesis from Nitrile & Amine:Using Methanol as C1 Source
N-Formamide synthesis using methanol: mechanistc aspect
Ph C N + CH3OHRuH2(CO)(PPh3)2(IiPr) (5%)
Ph NH
H
O
Benzene, 80 C12 equiv.Benzonitrile
◦ Reaction Profile Study
0 20 40 60 80 100 120 140 160 180 2000
20
40
60
80
100
am
ou
nt
(%)
Time (min)
Benzonitrile Formamide Benzylamine N-Benzylidene benzylamine
Ph N Ph
N-Benzylidene benzylamine
Ph NH + Ph NH2
NH3
Benzylamine
Explanation for side product generation
◦ Deuterium Labelling StudyRuH2(CO)(PPh3)2(IiPr) (5%)
Benzene, 80 CPhCN + CD3OD Ph N
HD(86%)
OD(50%)
D(66%)5 equiv.
59 %
R C N R NH2
2 CH3OH
2 [Ru]2 [Ru]H2
CH2O
CH2O
[Ru]R N
HH
O[Ru]H[Ru]H2
R NH
H
O
: Hydrogen transfer from methanol to nitrile !
RuH2(CO)(PPh3)2(IiPr) (5%)
Benzene, 80 C, 1 hPhCN + CD3OD Ph
CN
D(34%)5 equiv.
CD3OH+
: RuH2 mediated activation of nitrile α carbon !
◦ Proposed Mechanism
◦ N-Formylation with formaldehyde is also possi-ble! RuH2(CO)(PPh3)2(IiPr) (5%)
Benzene, 80 C- H2
Ph NH2 +
2 equiv. 75 %
CH2O n Ph NH
H
O
Summary
R OH + R' CN
oxidation reduction
R' NH2+RCOOH
R NH
O
R'
coupling reagent
Single-Step, CatalyticRedox-NeutralFacile Isotope Labeling100% Atom Economy
Ru Catalyst
stoichiometric reagentsby-products (wastes)
R1 CN +HO
HON
O
O
R1 + 2H2
R2
R3
R2
R3
[Ru]
[M]
[M-H2]
H2
R R' R'
HN
OHRor
R R' R'N
ORor
H O
OR
O O
ROH CH3OH
OO
O
well known process
+
+
HHCO2
R
HOR
OH
[Ru], K2CO3
Transfer Hydrogenation
TON up to 16600
TON up to 3240
[Ru], K2CO3
ROH
O
R
H2
CH3OH
R C N
R NH2
+ CH3OH R NH
O
H
+ CH3OH R NH
O
H- 2 H2
[Ru]
[Ru]
Atom-, Redox-, Step-Economy
Catalysts for Change!
Classical Chemical Synthesis
CatalysisSustainable Chemical
Synthesis
Prof. Hajime Hirao (computional study)
Dr. Xiangya XuDr. Zhenqian Fu
currentJeong-Bin LeeByungjoon KangSeung Hyo KimKicheol KimJaewoon KimJungwon KimSeoksun KimSangseung ParkMinha KimSang Min KimGunsoon Kim
alumniDr. Jong-Tai HongBenjamin PooiHansoo Song
R R'
OH
R R'
O+ H2
Fe(acac)3 8.5 mol%1,10-phenanthroline 8.5 mol%
K2CO3 8.5 mol%
toluene 0.5 mLreflux, 48 h
0.4 mmol
OH OH
MeO
OH
F3C
OH
Br
OH
Cl
OH
I
OH OH
Cl
OH
OMe
OH OH OH
>99% >99% >99% >99% >99% 93%
70% 87% 97% 94% 87% 93%
Fe-catalyzed Dehydrogenation
ACS Catalysis 2014, 4, 2889-2895
Hansoo Song
FeHN
PiPr2
PiPr2
BrCO
H
FeN
PiPr2
PiPr2
CO
H
Jones, J. Am. Chem. Soc. 2014, 136, 8564
FeOC
OCCl
NH
R2R1N
R
OH
CH3OH
Beller, Angew. Chem. Int. Ed. 2013, 52, 14162 Nakazawa, Chem. Comm. 2014, 50, 7941
Amide Synthesis with Complete Atom Economy
Direct Amide Synthesis from Nitrile and Alcohol
Catalytic Species Identification
Developed Catalytic System
RuH2(CO)(PPh3)3NHC Precursor
NaH
Proposed Catalytic Species ! (Observed with proton NMR)
Ru
H
NN
OC PPh3
Ph3P H
Verif ication
[Ru]IiPr
NH
O
CN
+OH
(5 mol%)
toluene reflux, 48 h 90 %
In-situ NMR Study
benzene reflux withnitrile and alcohol
Ru
H
NN
OC
Ph3P H
N
N+
[Ru](IiPr)2
Ru
H
NN
OC PPh3
Ph3P H
J. Am. Chem. Soc. 2013, 135, 11704
Mechanistic Difference
HOOH + RNC
hydrogen tranfer
[Ru]
O
O
RH2N
2H2
+
O
NH
OH
R
NR
O
O
2H2-
O
NH
O
R
H2
NR
OH
O
H2
[Ru]
[Ru]H2
N
R
H
[Ru]
H
N
R
H
[Ru]
H
R'CH2O H
N
R
H
[Ru]
H
H2O
H
R'
R' NH
O[Ru]H
R
R CN
R'CH2OH
R' NH
O
RN
R
HH
+
[Ru]
[Ru] = [Ru(NHC)Ln]
Hydrogen Transfer as a Substrate-Activating Strategy
O
O
+H2N
N
O
O
Ph
additives (10 mol%)
benzonitrilebutanediolyield (%)entry
1
2
3
4
x
o
o
o
x
x
x
o
trace
11
5
76
additive
RuH2(PPh3)4 (5 mol%) N NBr
(5 mol%) NaH[Ru] = (20 mol%)
Org. Lett. 2014, 16, 4404-4407.
N-Formamide Synthesis from Nitrile & Amine: Using Methanol as C1 Source
Catalytic nitrile alpha position activation
R CN
H+ [M]
R CN
H
[M] R CN
E
- [M]
[M]H
R CN
E
◦ General Concept
+EtO2C CN
CHORuH2(PPh3)4 (3%)
THF, rtCN
CO2Et
S. Murahashi, J. Am. Chem. Soc. 1995, 117, 12436
+[Ni] (3%)
THF, rt
H. Guan, Angew. Chem. Int. Ed. 2013, 52, 7523
CH3CN R OR
OH
CN
O
O
Ni CH2CN
PHiPr2
PHiPr2
[Ni]
+
[Rh(OMe)(cod)]2 (1%)PCy3 (4%)
DMSO, rt, 6h
S. Saito, Chem. Commun. 2008, 2212
CH3CN R O R
OH
CN
+rt, 6h
S. Paganelli, Tetrahedron Lett. 1991, 32, 2807
Ph CNCOOMe HRh(CO)(PPh3)3 (1%)
COOMePh
CN
3
◦ Selected Examples
OH
OO
O
HO
O
OH
O H
O
HO
O
OO
H
O
HMeOH
OH
OH
H2 H2
H2
H2
HOOH
HO OH
- H2
HN
PPh2
PPh2
RuCO
H
Cl
N
PPh2
PPh2
RuCO
H
O
HH
N
PPh2
PPh2
RuCO
H
HN
PPh2
PPh2
RuCO
H
H
R
O
R'
R
O
K2CO3
R
O
R'
TS
R
R'
R
O
R'
+ H2
- H2
R'
H
H
H
H
-HCl
140 oC, 3 h
[Ru] (0.5 mol%)K2CO3 (0.5 mol%)
OO
O
MeOH(D)
H/DH/DH2 / (CD3)2CDOD
+ (D)HOOH(D)
H2 (bar) H2/propanol-d8 MeOH (%, H/D) diol (%, H/D)
0
3
9
35
10:90
25:75
56:44
89 (2:98)
90 (8:92)
93 (21:79)
98 (54:46)
99 (2:98)
99 (7:93)
99 (23:77)
99 (62:38)
Mechanism Study
ACS Catalysis 2014, 4, 3630-3636.