Chemistry of MetalsCatalysis for Sustainable Development

Michael W.-Y. YuDepartment of Applied Biology and Chemical Technology

The Hong Kong Polytechnic University

Chemistry is a unique science….

Drugs for better healthcare

Man-made fibers and materials for high performance apparel

Materials for device fabrication

Optical fiber for high speed communication

Chemical Synthesis improves quality of life

Most chemical products — from perfumes to plastics to pharmaceuticals — are

based on carbon, which currently is supplied by Earth's finite petroleum feedstocks

Industrial chemical processes generate large amounts of waste, the safe disposal of which imposes an increasing burden on the environment

We are facing challenges that our quality of life is becoming Unsustainable …..

Green Chemistry for achieving Sustainable Development

Innovation in catalysis… a route to green chemical synthesis

Catalysis speeds up a reaction, and can

also make new reactions possible that allow different starting materials to be used.

90% of industrial processes for production of fuels, plastics, drugs and other chemicals relies on catalysis

Development of new catalysts is critical for the development of more efficient, economic and greener technologies.

Catalysis – less energyEmploy non-toxic reagents and less wastes

Development of Metal Catalysis for sustainable development….. Hydrogen as fuel for tomorrowo Fuel cell technologyo Solar energy production of hydrogen

Chemical Synthesis via Activation of Inert Chemical bondso Activation of H-H bondo Activation of C-X (X = halide)o Activation of C-H bond

Hydrogen as fuel for tomorrow

Renewable Energy for the Future

• Highly exothermic reaction• Inexhaustible• Non-polluting• Zero carbon emission

Dihydrogen (H2)

2H2 + O2 2H2O

10

What is a fuel cell?• Fuel is reacted with oxygen in an

electrochemical cell to produce energy.– Electricity is generated from oxidation of fuel supplied to

the anode and reduction of oxygen at the cathode.

• Controlled process!!!Oxidation of hydrogen:

cathode: O2(g) + 4e- + 4H+ 2H2O

anode: 2H2(g) 4H+ + 4e-

Each of the anode and cathode reactions are half-cell reactions.The overall cell reaction is: 2H2 + O2 2H2O

11

Catalyst

Anode Cathode

O2H2

electrolyte

e-

H2O

Schematic diagram of fuel cell

A fuel cell works by catalysis, oxidizing the fuel on anode, and forcing the electrons pass through a circuit, hence converting them to electrical power

At the cathode, the oxidant (oxygen) is reduced and takes the electrons back in, combining them with protons to give water

• In acid medium, most metal cannot operate in such condition metal dissolution

• Noble metal (Pt) oxidation / reduction of surface within the potential range of interest

H2 oxidation

O2 reduction– 4 e- + 4 H protons

reduction (complex systems)

– O2 H2O2 or H2O

12

Electron flow

H+

H+

H+ O2

WaterH2O

H2

Proton exchange membrane

Gas permeable electrode with platinum catalyst

Gas permeable electrode with platinum catalyst

2H2 4H+ + 4e-

O2 + 4H+ + 4e- 2H2O

The PEM fuel cell

A proton-exchange membrane (PEM) is used to separate the anode and cathode

Allows H+ to pass through while keeping the gases apart The protons reach cathode and react with oxygen to form water — the

only waste product is water, which is environmentally benign

13

The H2/O2 fuel cell is ideal for driving environmentally friendly vehicles with

zero carbon emission

• Suitable for urban transportation.

Challenges:

1. Platinum is a rare metal$$$$ The operation cost of fuel cell becomes high CO poisoning with low tolerance

Development of new electrocatalysts for fuel cell becomes important!

- reducing platinum loading – metal alloy with Pt

- development of novel Pt-free materials like metal oxide-based catalystMo2C-ZrO2/C, transition metal marcocyclic compounds

2. Storage of hydrogen onboard

H2 gas oxidation

1. Mass transport of dissolved H2 to the surface:

H2(aq) H2(ads)

2. Chemisorption of hydrogen as atoms (breaking H-H bond) H2(aq) 2H(ads)

3. Ionization of hydrogen atoms H(ads) H+

(ads) + e-

4. Transport of the H+ ions away from the electrode surface H

+(ads) H+

(aq)

14

H2(g) → 2H(g) DH = +436 kJ mol-1

Oxygen reduction

1. Large kinetic barrier for the oxygen reduction strong O=O bond: BDE = 463 kJ mol-1

2. For some electrocatalysts (Ag or Pt), two parallel reaction pathways are observed:

– Direct reduction of O2 to H2O (acid medium)

Eo = 1.23V

– An indirect reduction of O2 to H2O2 (acid medium)

Eo = 0.68V

15

2H2OO2 + 4H+ + 4e-

H2O2O2 + 2H+ + 2e-

Catalyst is needed….

• For dioxygen reduction reaction to take place, the

dioxygen bond must be weakened, • A strong interaction with the surface of the catalyst will

be necessary

– Electrocatalyst becomes important in the selectivity of product.

16

Binding of dioxygen to metal

• End-on

• Side-on

• Bridging

17

O O

M

M

O

O

O O

MM

Dioxygen is bonded to metal atom with π bond of O2 and metal surface.

Two bonds are formed with two metal centres in each end of the O2 molecule.

Dioxygen molecule is bonded between metal atom with bent structure.

Binding of O2 to metal leads to weakening of the O-O bond

M-O2 complexes are reactive…

18

Overall result: Breaking of O=O bond to form 2H2O molecules

Mn+ O2

O

Mn+1

O Mn+ H2O2

Mn+ 2H2O

2e-/2H+

4e-/4H+superoxo

O O

Mn+2

peroxo

4e-/4H+

Mn+ 2H2O

O O

Mn+1 Mn+1

bridging peroxo

4e-/4H+

2Mn+ 2H2O

Where does the H2 come from…?

• Steam Methane Reforming High-temperature (800 – 900 oC) steam is

combined with methane in the presence of a Ni catalyst to produce hydrogen. This is the most common and least-expensive method of production in use today

• Water is the most abundant source of Hydrogen

2H2O(l) 2H2(g) + O2(g) DH = 285.9 kJ mol-1

• Turning water to H2 is a highly endothermic process

• Dependent on Fossil Fuel• CO2 emission!!!

Water electrolysis

• Zero carbon emission??• Great demand of high

quality water• Expensive

Learning from Nature….

• Higher green plants use solar energy to convert H2O into O2 and reducing equivalents in NADPH for reduction of CO2 to carbohydrates…

• This process is known as Photosynthesis

2H2O + 4hn O2 + 4H+ + 4e-

nCO2 + 2ne- + 2nH+ (CH2O)n

22

Chlorophyll – pigments for Photosynthesis

• Macrocyclic structure • Conjugated C=C bond• Mg2+ cation (structure stabilization)

23

hn

Ground state

p bonding

*p antibonding

chlorophyllExcited state

p bonding

*p antibonding

chlorophyll

A

electron transfer

“hole” – oxidizing!!

radical anion – reducing!!

chlorophyll cation

p bonding

*p antibondingA-

charge separation

Chlorophyll captures light

energy to form reactive chemical species….

Light Reactions

2H2O O2 + 4H+ + 4e-

• Active site (Oxygen Evolving Center) contains a Mn4 cluster• Four photons are required to effect 4e oxidation of 2H2O molecules

Oxygen Evolving Center (OEC) of PSIIFerreira, K. N., Iverson,T. M., Maghlaoui, K., Barber, J., Iwata, S. Science 2004, 303, 1831

• Light drives the oxidation of Mn to higher oxidation states• Highly oxidizing Mn would damage the associated proteins of the PSII complex;

protein being replaced every 30 minutes

Artificial Photosynthesis

Design a man-made catalytic system that mimics Nature for photo-driven water oxidation…

DyeA D OEC

e-e-e-e-

2H2O

O2 4H+

HEC

2H+

H2

e-

e-

anode cathodepermeablemembrane

hn

Dye-sensitized photovoltaic cells

• Photoexcitation of dye is followed by electron injection into the conduction band of the TiO2 film

• The dye is regenerated by a redox system (e.g. I- / I3- couple)

Ruthenium complexes as dye for photovoltaic cells

• Stable complexes, over 100 million turnovers (servicable for 20 years)• Carboxylic acid groups for metal anchoring to TiO2 (key to charge injection)• Tunable color by structure modification• Wide absorption range [400 (visible) – 900 nm (near IR)]

Figure extracted from Gratzel, M. Inorg. Chem. 2005, 44, 6841

Working principle

• Photoexcitation causes charge separation between Ru and the ligand Ru becomes one-electron oxidized; ligand becomes one-electron reduced

• Excited state is a stronger oxidant and reductant than its ground state

Ground state

d p (Ru)

*p ligand

[Ru(bpy)3]2+

Excited state

d p (Ru)

*p ligand

[Ru(bpy)3]2+*

formally Ru3+ center

formally one-electron reduced ligand

hn

Photoelectrochemical dehydrogentaion of alcohol and generation of hydrogen

• Electrochemical isopropanol oxidation by Ru-oxo• Platinum electrode for 2H+/H2 couple• Electrochemical water oxidation remains a challenge

[Ru(dpp)RuII(H2O)]4+TiO2

2H+ H2

photoanode

h

[Ru(dpp)RuIV=O]4+TiO2

[Ru*(dpp)RuII(H2O)]4+TiO2

e- e-

[Ru(dpp)RuII(H2O)]4+TiO2

cathode

2e- Pt

OH

O

ACTIVATION OF DIHYDROGENMetal-dihydrogen interaction

Alkene Hydrogenation

• Exothermic reaction (DH ~ 120 kJ mol-1)• Catalyst required: Pt, PtO2, Pd• Syn addition to C=C bond• BDE (H2) = 436 kJ mol-1 (critical reaction barrier)• C.f. BDEs (kJ mol-1) for: Cl-Cl (242); C-H (414)

catalystC C C C

H H

H H

weak p-bond strong s-bond

2 X strong s-bonds

Waste-free reaction!

• Metal-hydride formation from “M + H2”?

• Coordination of H2 to M

• Breaking of H-H bond• M-H covalent, polarized, reactive!!• c.f. 2Na + H2 2NaH

H-H cleavage

LnM H2 LnMH

HLnM

H

H

-+

metal-dihydrogen complex

metal-hydride (H-)

Rh-catalyzed homogeneous alkene hydrogenation

Ph3PRh

Ph3P

H

Cl

PPh3

H

Ph3PRh

Ph3P

H

Cl

H

18-electron, coordinatively saturated

16-electron, coordinatively unsaturated

PPh3Ligand DisscoiationIII III

Ph3PRh

Ph3P

H

Cl

H RhPh3P

HPPh3

HCl

Metal-Alkene -Complex

Ph3PRh

Ph3P

H

Cl

CC

H

Hydride Insertion

Metal-Alkyl Complex

Reductive Elimination

Ph3PRh

Ph3P

ClI III

IIIIIIAlkene Coordination

H2

H H

Reversible changes of oxidation states: RhI RhIII

• Preparation of stereochemically pure compounds• Enantiomers have different binding properties to

receptors thereby exhibiting different bioactivities• Hazard of serious side-effect (e.g. thalidomide)• Diastereomeric resolution (max. yield 50%)

Chiral Technology for Drug Synthesis

Asymmetric Hydrogenation

• Chiral ligands

Ph2PPPh2

P

P

Et

EtEt

Et

Me

Me O

OPPh2

PPh2

H

H

**

DIPAMP (chiral at phosphorus)By Knowles in 60s(Nobel 2001)

DIOP (chiral at backbone)By Kagan in 70s

BINAP(Axially chiral backbone)By Noyori in 80s(Nobel 2001)

DuPhos(chiral at backbone)By Burk in 90s

37

Asymmetric Hydrogenation: application

Practical application of asymmetric hydrogenation in Eli Lilly Company (Making drugs).

FeP

Me

CF3

CF3

CF3

CF3

PPh2

L* =

Peroxime proliferator activated receptor (PPAR) agonist, for treatment of diabetes.

COOH

OEtBnO

COOH

OEtBnOH2

[Rh(NBD)2]BF4

MeOH

L*

COOH

OEtO

O

HN

Me

Me

Houpis, Org. Lett. 2005, 7,

38

Ketone Hydrogenation

R OR'

O O

R OR'

OH O(R)-BINAP Ru(II)

H2 (70-103 atm)

93-100 % yield98-100 % ee

b-ketoesters:

Ru

RuP

P O

O

Cl

H

H3C

OCH3

(R)

P

P

Cl

H

O

O

OCH3(S)

higher energy

Murahashi, Chem. Rev. 1998, 98, 2599

H3C

lower energy

P

P PPh2

PPh2=

39

Ketone Hydrogenation: Examples

R Y

OO

R' R'

Y = OR, SR, NR2

R Y

OOH

R' R'

Asymmetric hydrogenation ofketo esters

PR (OR'')2

OO

R' R'

PR (OR'')2

OOH

R' R'

Asymmetric hydrogenation ofketo phosphonates

R

O

S

ONa

OO R

OH

S

ONa

OO

Asymmetric hydrogenation ofketo sulfonates

HYDROGENATION OF FUNCTIONALIZED KETONES

R

O

OHR

OH

OHAsymmetric hydrogenation ofhydroxy ketones

R

O

NR'2 R

OH

NR'2Asymmetric hydrogenation ofamino ketones

40

Ketone Hydrogenation: Selected practical examples

O

O

N

MeO OMe

COPh

trans-RuCl2[(R)-Xyl-BINAP][(R)-DAIPEN]

t-BuOK, i-PrOH, 25 ¢XC, 8 atm H2

O

OH

N

MeO OMe

COPh

97% ee>99% yield

HO

OH

NH

MeO OMe

HCl

(R)-denopamine

O

OO

Me

Me

OTBS

MeO

O O

glycoside derived -keto ester

O

OO

Me

Me

OTBS

MeO

O OH

(S)-config. (R)-config.

O

OO

Me

Me

OTBS

MeO

O OH

%dr (S)/(R) = >99/1

%de = >98%

RuBr2[(R)-BINAP]

45 oC, 1 atm. H2

MeOH, 24 h

Thomassigny, C.; Greck, C. Tetrahedron: Asymmetry 2004, 15, 199.

Kawaguchi, T.; Saito, K.; Matsuki, K.; Iwakuma, T.; Takeda, M. Chem. Pharm. Bull. 1993, 41, 639.

ACTIVATION OF ARYL HALIDESFormation of Reactive Organopalladium Complexes

Biaryls are important targets for organic synthesis

Biaryls

Cross Coupling Reactions – little by-products

• Aryl halides are poor electrophiles for SN1 / SN2• Due to sp2 hybridized C-X bond:

– Lower polarity – Stronger C-X bond

• Catalyst is required for Biaryl Coupling Reactions

X

M = main group element(e.g. Li, MgX, B, Sn)

nucleophileelectrophile C-C bond formation

A AB B

X = halide

M

PR3

PdR3P

R3PPR3

0

four-coordinate18e species

2 PAr3

PR3

Pd

PR3

two-coordinate14e species

X R3P

Pd

R3P X

four-coordinate16e species

R3P

Pd

PR3X

isolated trans-complex

0 II II

d10 d8

R3P

Pd

R3P X

Oxidative Addition

concerted three-center T.S.

Oxidative Addition turned Aryl Halides to reactive Arylpalladium

Favored by strong s-donors (alkyl vs aryl phosphines)

Rate : tBu3P > Ph3PReactivity trend: C-I > C-Br >>> C-Cl >>> C-Fc.f. Mg + ArX ArMgX (Grignard reagent)

Coordinatively unsaturatedElectron rich

Stable square planar complex

45

Suzuki coupling reaction

X

X = I, OTf, Br, Cl(recent application)

R

palladium complex

base(R'O)2B

R R''R''

Developed in early 80s, by Akira Suzuki.

Suzuki, Chem Rev. 1995, 95, 2457.Suzuki, J. Organomet. Chem. 1999, 576, 147

Catalytic cycle

• Oxidative addition: Pd(0) Pd(II) + C-X bond breaking • Ar’ group transfer from B Pd “transmetallation”• Reductive elimination: C-C bond formation step + Pd(0) regeneration

Pd(0) Ar-X

Pd(II)X

ArPd(II)Ar'

Ar

Ar Ar'

Ar'-MMX

General catalytic cycle for cross coupling

M = borate

oxidative addition

transmetallation

reductive elimination

Examples

Muller, D.; Fleury, J-P. Tetrahedron Lett. 1991, 32, 2229

(OH)2B O

NEt2

CONEt2

Br

O

NEt2

CONEt2

Pd(PPh3)4

Na2CO3

DME, reflux

Fu, J-M.; Sharp, M. J.;Snieckus, V. Tetrahedron Lett. 1988, 29, 5459

CN

Cl (OH)2B

CN NN

NNH

N

O

HO2C

Valsartan (antihypertensive drug)

Na2CO3H2O/toluene/dmso 120 oC

PdCl2 / L

89% yieldca. 2000 TON

P

HO3S

SO3H

HO3S

L =

Haber, S; Egger, N. US Patent 2000, 6-140-265

O

B(OH)2

RO

OR O

OR

OMeO

OMe O

OR

IPdL4

K2CO3

L = phosphine ligand

O

OR

OR

O

RO

OMeO

OMe O

OR

95% yield

Ligands for Suzuki Coupling Reactions

• Strong s-donors promote oxidative addition• Steric bulkiness of ligand increase activity of Pd(0) – more

open for substrate interaction

P

3

P

3P R

2

R = BuR = Me

CH3

P

3

PR2

R = PhR = CyR = tBu

PCy2

Fe

Ph

PhPh

PhPh

PtBu2

N

N

RR

R'

RR

R'

PCy3 PtBu3P(oTolyl)3

Q-Phos

N-heterocyclic carbene

R, R' = MeR = iPr, R' = H

ACTIVATION OF C-H BONDThe Next Challenge

• Using pre-functionalized substrates (e.g. aryl halides)• Expensive• Derived from simple aromatics by halogenation

Coupling reactions with C-H bond???

H MA Bcatalyst

A B

Strong bond energyNon-polar

Formation of Arylpalladium from arenes

• Electrophilic attack of Pd2+ on arenes leads to C-H bond cleavage• pKa: 44 (butane); 37 (C6H6); • Limitation: homocoupling; isomeric products

PdCl2NaOAc

HOAc, heat

Pd

H

X

HX

Pd X

X

X = Cl- or OAc-

HX

Pd

II

II

Pd(0)

oxidants

electrophilic attack by Pd2+

deprotonation

reductive elimination

Cyclopalladated Complexes

• Cyclopalladation of arenes [Ryabov, A. D. Chem. Rev. 1990, 90, 403]

• Five-membered metallacycle

• Example:

C HPd2+

H+

cyclopalladated complex

D

CPd

D

D = donor group (e.g. O, N)

N MeOH NPd OAc

2

+ Pd(OAc)2r.t.

Results from W.-Y. Yu (PolyU)

Suzuki Coupling via C-H Activation

N

O CH3

HN

O CH3

Ar

Ar B(OH)2Pd(OAc)2 (5 mol%), Cu(OTf2) (1 equiv)

Ag2O (1 equiv), toulene, 120oC, 24h(2 equiv)

Shi, Z. and co-workers, Angew. Chem. Intl. Ed. 2007, 46, 5554

Yu, J.-Q. and co-workers, J. Am. Chem. Soc. 2007, 129, 3570

• Using Pd(II) salt as catalyst• Oxidizing agents: Ag(I), Cu(II), benzoquinone

CO2Na

HAr B

O

O

Pd(OAc)2 (10 mol%), benzoquinone (0.5 equiv)

Ag2CO3 (1 equiv), tBuOH, 120oC, 3h

Me

CO2Na

Ar

Me

(1 equiv)

Direct C-H Arylation Methods

Pd(OAc)2 (5 mol%)

AgOAc (1 equiv),

HN

O

Et

I tBu

Br CF3CO2H, 110-120oC

NH

O

Et

Br

tBu

Daugulis, O. and co-workers, J. Org. Chem. 2007, 72, 7720

NH

I+ Ar

BF4-

Pd(OAc)2 (10 mol%),

AcOH,100oC, 12h NAr

Sanford, M. and co-workers, J. Am. Chem. Soc. 2005, 127, 7330

NH

ArO

O O

OAr

Pd(OAc)2 (10 mol%),

CH3CN, AcOH,100oC, 2h(2 equiv)

NAr

Yu, W.-Y. and co-workers @ PolyU (Org. Lett. 2009, 11, 3174 )

Activation of inert chemical bond by metal

• Coordination of stable H-H, C-X and C-H to transition metal

• Weakening of the bonding in reagent molecules

• Generation of reactive “M-reagent” species

MM

Stable Reactive

Activation stepsubstrate

product

Catalysis and Sustainable Development

By catalysis, we can.. Design processes for developing renewable energy technologies Synthesize value compounds from raw materials

o Cost effective (fewer steps)o Environmental friendly (atom economy, no toxic wastes)

Role of metal ion in catalysis Non-redox metal ion (e.g. Mg2+) provide structure support for the

active site Redox active metal ions mediate multiple electron transfer reactions

for oxidation and reduction of substrates Variable oxidation states and coordination mediate bond breaking

and bond formation

Thank You!!