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.