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Poater, A.; Cavallo, L. Theor. Chem. Acc. 2012 , 131 , 1155. Deactivation Pathways in Transition Metal Catalysis Why Study Catalyst Decomposition? active for catalysis inactive for catalysis decomposition "One of the reasons for [the] limited understanding [of catalyst deactivation] is that academic groups usually focus on the more rewarding improvement of activity and/or selectivity of a catalyst, since more or less rational strategies can be followed, rather than investing resources to follow catalyst deactivation along unexplored pathways."

Deactivation Pathways in Transition Metal Catalysis · Deactivation Pathways in Transition Metal Catalysis Why Study Catalyst Decomposition? active for catalysis inactive for catalysis

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Poater, A.; Cavallo, L. Theor. Chem. Acc. 2012, 131 , 1155.

Deactivation Pathways in Transition Metal CatalysisWhy Study Catalyst Decomposition?

active for

catalysis

inactive for

catalysis

decomposition

"One of the reasons for [the] limited understanding [of catalyst deactivation] is that academic groups usually focus on the more rewarding improvement of activity and/or selectivity of a catalyst, since more or less rational strategies

can be followed, rather than investing resources to follow catalyst deactivation along unexplored pathways."

0.0

10.0

20.0

30.0

40.0

50.0

60.0

70.0

80.0

90.0

100.0

0 10 20 30 40 50 60 70 80

% C

atal

yst

Number of Cycles

Deactivation Pathways in Transition Metal CatalysisWhy Study Catalyst Decomposition?

What happens if you lose 10% of your catalyst each cycle? 5%? 2%?

Deactivation is much more studied in industrial

settings where low catalyst loadings are critical.

Even a modest improvement can have a large effect on TON!

Crabtree, R. H. Chem. Rev. 2015, 115 , 127.

Deactivation Pathways in Transition Metal CatalysisWhy Study Catalyst Decomposition?

decomposition

But first, some definitions:

Irreversible processes that involves extensive breakup of bonds in a chemical structure:

n Degredation: deletirious ligand functionalization or bond rupture

n Decomposition: collapse of the metal complex as a whole

n Deactivation: permanent loss in catalytic activity

n Inhibition: reversible process that leads to loss in activity

Crabtree, R. H. Chem. Rev. 2015, 115 , 127.

Deactivation Pathways in Transition Metal CatalysisA Scarce Topic in the Literature

Ligand loss or deleterious functionalization

Multimetallic processes, cluster formation

Catalyst poisons

Substrate or product inhibition

LnPd(0)

MN

N

N

NM

CN– CO thiols O2

N

BrN

O

Deactivation Pathways in Transition Metal CatalysisOutline

N N

RuCl

H2Ir

L

IrH2

PCy3PCy3

L

L

Cy3P

HH2Ir

2+

IrIII

N

NN

2+

N

Hydrogenation Cross Metathesis Photoredox

Xu, Y.; Mingos, M. P.; Brown, J. M. Chem. Commun. 2008, 199.

Deactivation Pathways in Transition Metal CatalysisCrabtree's Catalyst

IrN

PCy3

+ Crabtree's Catalyst

n discovered in 1977n reactivity for tetrasubstituted olefins

MeMe

Me Me

Me

Me

catalyst

RhCl(PPh3)3

[Rh(cod)(PPh3)2]PF6

[Ir(cod)PCy3(py)]PF6

TOF (mol substrate per mol cat. per hour)

60 70 0 0

4000 10 0 0

6400 4500 3800 4000

Brown, J. M. Angew. Chem. Int. Ed. Engl. 1987, 26, 190.

Deactivation Pathways in Transition Metal CatalysisCrabtree's Catalyst

IrN

PCy3

+

C

A B

D H2, CH2Cl2

A B

C DH H

Me

OHMe

Me

OHMe

20 mol% cat, 99:1 dr

Me CO2Me Me CO2Me

2 mol% cat, 89:11 dr

Verendel, J. J.; Pàmies, O.; Diéguez, M.; Andersson, P. G. Chem. Rev. 2014, 114 , 2130.

Deactivation Pathways in Transition Metal CatalysisCrabtree's Catalyst

Ir

H

S

py

H

PCy3

S

Ir

H

S

py

H

PCy3

Ir

H

S

py

H

PCy3 migratoryinsertion

Ir

S

py

H

PCy3

H

reductiveelimination

SH2

H3CCH3

Ir

S

H

py

H

PCy3

Ir

H

py

H

PCy3

Ir

H

py

H

PCy3 migratoryinsertion

reductiveelimination

S

H3CCH3

Ir

H

H

py

H

PCy3

H

H H

HH

H2

IrI/IrIII IrIII /IrV

Verendel, J. J.; Pàmies, O.; Diéguez, M.; Andersson, P. G. Chem. Rev. 2014, 114 , 2130.

Deactivation Pathways in Transition Metal CatalysisCrabtree's Catalyst

Ir

H

S

py

H

PCy3

S

Ir

H

S

py

H

PCy3

Ir

H

S

py

H

PCy3 migratoryinsertion

Ir

S

py

H

PCy3

H

reductiveelimination

SH2

H3CCH3

Ir

S

H

py

H

PCy3

Ir

H

py

H

PCy3

Ir

H

py

H

PCy3 migratoryinsertion

reductiveelimination

S

H3CCH3

Ir

H

H

py

H

PCy3

H

H H

HH

H2

IrI/IrIII IrIII /IrV

Ir

Xu, Y.; Mingos, M. P.; Brown, J. M. Chem. Commun. 2008, 199.

Deactivation Pathways in Transition Metal CatalysisCrabtree's Catalyst

H2Ir

L

IrH2

PCy3PCy3

L

L

Cy3P

HH2Ir

2+

H2, CH2Cl2

low [alkene]–

K2PtCl4

N

PCy3

+

n bulkier ligands can prevent trimerisation through steric hindrance

n low catalyst concentration can prevent trimerisation

n complexes with BArF counterion rather than PF6 are less moisture sensitive

Lightfoot, A.; Schnider, P.; Pfaltz, A. Angew. Chem. Int. Ed. 1998, 37, 2897.

Deactivation Pathways in Transition Metal CatalysisCrabtree's Catalyst

H2, CH2Cl2

n complexes with BArF counterion rather than PF6 are less moisture sensitive

P NIr

O

tBu

o-tolo-tol

+ X–

Me

MeO

Me

MeO

X– mol% cat. conditions conversion %

PF6–

PF6–

BArF–

4%

4%

0.3%

rigorously dry

57%

99%

99%

Deactivation Pathways in Transition Metal CatalysisOutline

N N

RuCl

H2Ir

L

IrH2

PCy3PCy3

L

L

Cy3P

HH2Ir

2+

IrIII

N

NN

2+

N

Hydrogenation Cross Metathesis Photoredox

Deactivation Pathways in Transition Metal CatalysisOlefin Metathesis Catalysts

EtO2C CO2EtCO2EtEtO2C metathesis cat.

Schrock Chauvin Grubbs

PCy3

RuCl

PCy3

Cl

Ph 10 minutesPCy3 [Ru]

H2N NH2

unidentified, inactivebyproducts

Moore, J. S. et. al. Adv. Synth. Catal. 2009, 351, 1817.

Deactivation Pathways in Transition Metal Catalysis

Olefin Metathesis Catalysts

unstable to:

n coordinating solvents (MeCN, DMSO, etc.)

n lewis basic functionality

n amines in particular

PCy3

RuCl

PCy3

Cl

Ph

Grubbs generation I

PCy3

RuCl

PCy3

Cl

Ph 10 minutesPCy3 [Ru]

H2N NH2

unidentified, inactivebyproducts

Moore, J. S. et. al. Adv. Synth. Catal. 2009, 351, 1817.

Deactivation Pathways in Transition Metal CatalysisOlefin Metathesis Catalysts

RuR

RuR

RR Ru products

Bimolecular Catalyst Decomposition

Crabtree, R. H. J. Organomet. Chem. 2005, 690, 5451.

Deactivation Pathways in Transition Metal Catalysis

Olefin Metathesis Catalysts

P

P

Me

MeMe

iPr

iPr

iPrMeO

OMe

PCy2N

Me

MeMe

NMe

MeMe

widely studied 2 e– spectator ligand

sterically and electronically tunable

strong σ-donor, weak π-acceptor

very tight binding to metal

sterically large ligand

Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18.

Deactivation Pathways in Transition Metal Catalysis

Olefin Metathesis Catalysts

RuCl

PCy3

Cl

Ph

NN MesMes

Functional Group Tolerance

R

O

OHRHO O

HHR

O

HR

O

R R

O

NH

RR

O

OR

Moore, J. S. et. al. Adv. Synth. Catal. 2009, 351, 1817.

Deactivation Pathways in Transition Metal Catalysis

Olefin Methathesis Catalysts

RuCl

PCy3

Cl

Ph

NN MesMes

RuCl

NH

Cl

Ph

NN MesMes

HNMe

Me

4 5

CO2EtEtO2C

RCM

ROMP

NH2Me

Moore, J. S. et. al. Adv. Synth. Catal. 2009, 351, 1817.

Deactivation Pathways in Transition Metal Catalysis

Olefin Metathesis Catalysts

RuCl

PCy3

Cl

Ph

NN MesMes

RuCl

NH

Cl

Ph

NN MesMes

HNMe

Me

4 5

CO2EtEtO2C

RCM

ROMP

NH2Me

bulky small

Ireland, B. J.; Dobigny, B. T.; Fogg, D. E. ACS Catal. 2015, 5, 4690.

Deactivation Pathways in Transition Metal Catalysis

Olefin Metathesis Catalysts

NN MesMes

RuCl

OCl

iPr

1 mol%

amine (n mol%)PhH, 60 ºC, 24 h

Ph PhPh

Ireland, B. J.; Dobigny, B. T.; Fogg, D. E. ACS Catal. 2015, 5, 4690.

Deactivation Pathways in Transition Metal CatalysisOlefin Metathesis Catalysts

RuCl

L

Cl

Ph

NN MesMes

L

H2NR

RuCl

L

Cl

Ph

NN MesMes

LH2N R Ru

ClL

Cl

NN MesMes

L RuCl

L

L

Cl

NN MesMes

L

Benzylidene abstraction

+ L

Ph NH

R

Lummiss, J. A. M.' McClennan, W. L.; McDonald, R.; Fogg, D. E. Organometallics 2014, 33, 6738.

Deactivation Pathways in Transition Metal Catalysis

Olefin Metathesis Catalysts

Ireland, B. J.; Dobigny, B. T.; Fogg, D. E. ACS Catal. 2015, 5, 4690.

Deactivation Pathways in Transition Metal CatalysisOlefin Metathesis Catalysts

RuCl

L

Cl

Ph

NN MesMes

L

H2NR

RuCl

L

Cl

Ph

NN MesMes

LH2N R Ru

ClL

Cl

NN MesMes

L RuCl

L

L

Cl

NN MesMes

L

Benzylidene abstraction

+ L

Ph NH

R

Ireland, B. J.; Dobigny, B. T.; Fogg, D. E. ACS Catal. 2015, 5, 4690.

Deactivation Pathways in Transition Metal CatalysisOlefin Metathesis Catalysts

RuCl

L

Cl

Ph

NN MesMes

L

H2NR

RuCl

L

Cl

Ph

NN MesMes

LH2N R Ru

ClL

Cl

NN MesMes

L RuCl

L

L

Cl

NN MesMes

L

Benzylidene abstraction

+ L

Ph NH

R

Metallacyclobutane deprotonation

RuCl

Cl

R

H2IMes RuH2IMes

Cl

Cl Ph

RH

H

Ph

NR3RuH2IMes

Cl

Cl

R

PhHNR3+

R

Ph

Ru decomp.

Hong, S. H.; Chlenov, A.; Day, M. W.; Grubbs, R. H. Angew. Chem. Int. Ed. 2007, 46, 5148.

Deactivation Pathways in Transition Metal CatalysisOlefin Methathesis Catalysts

RuCl

PCy3

Cl

Ph

NN MesMes N N

RuCl

OCl

Me

Me

N N

RuCl

Cl

Ph

PCy3

EEMe MeEE

Me Me

metathesis catalyst

CH2Cl2, 24 h

yield = 0% yield = 76% yield = >95%

Hong, S. H.; Chlenov, A.; Day, M. W.; Grubbs, R. H. Angew. Chem. Int. Ed. 2007, 46, 5148.

Deactivation Pathways in Transition Metal CatalysisOlefin Metathesis Catalysts

RuCl

PCy3

Cl

Ph

NN MesMes N N

RuCl

OCl

Me

Me

N N

RuCl

Cl

Ph

PCy3

EEMe MeEE

Me Me

metathesis catalyst

CH2Cl2, 24 h

yield = 0% yield = 76% yield = >95%

Hong, S. H.; Chlenov, A.; Day, M. W.; Grubbs, R. H. Angew. Chem. Int. Ed. 2007, 46, 5148.

Deactivation Pathways in Transition Metal CatalysisOlefin Methathesis Catalysts

N N

RuCl

Cl

Ph

PCy3

40 ºC

CH2Cl2, 12 h

N

RuCl

N N

RuCl

N

24% 38%

Hong, S. H.; Chlenov, A.; Day, M. W.; Grubbs, R. H. Angew. Chem. Int. Ed. 2007, 46, 5148.

Deactivation Pathways in Transition Metal CatalysisOlefin Methathesis Catalysts

N N PhPh

RuCl

Cl

Ph

PCy3

N

Ru

NN

Ru

N

– PCy3N N PhPh

RuCl

Cl

Ph Cl

Cl H

Ph

NN

RuCl

Cl

Ph

Cl

Cl

C–H activation hydride insertion

R.E. 40 ºC

CH2Cl2, > 7 daysno reaction

Hong, S. H.; Chlenov, A.; Day, M. W.; Grubbs, R. H. Angew. Chem. Int. Ed. 2007, 46, 5148.

Deactivation Pathways in Transition Metal CatalysisOlefin Metathesis Catalysts

N

Ru

N

Cl

Cl

1.2 equiv PCy3

CH2Cl2, 36 h

N N

RuCl

quantitative

HPCy3+Cl–

PCy3 assistance required for second C–H insertion

Hong, S. H.; Chlenov, A.; Day, M. W.; Grubbs, R. H. Angew. Chem. Int. Ed. 2007, 46, 5148.

Deactivation Pathways in Transition Metal CatalysisOlefin Methathesis Catalysts

RuCl

PCy3

Cl

Ph

NN MesMes N N

RuCl

OCl

Me

Me

N N

RuCl

Cl

Ph

PCy3

EEMe MeEE

Me Me

metathesis catalyst

CH2Cl2, 24 h

yield = 0% yield = 76% yield = >95%

Deactivation Pathways in Transition Metal Catalysis

Olefin Metathesis Catalysts

RuCl

PCy3

Cl

Ph

NN MesMes

A metathesis catalyst that tolerates free amines has yet to be reported.

Deactivation Pathways in Transition Metal CatalysisOutline

N N

RuCl

H2Ir

L

IrH2

PCy3PCy3

L

L

Cy3P

HH2Ir

2+

IrIII

N

NN

2+

N

Hydrogenation Cross Metathesis Photoredox

Deactivation Pathways in Transition Metal CatalysisPhotoredox Catalysis

most organicmolecules

photoredoxcatalysts

absorb light fromordinary light bulbs

Targeted delivery of energy via selective excitation of photoredox catalyst

200 nm 300 nm 400 nm 500 nm 600 nm 700 nm

Visible lightUV light

IrIIIN

N

N

Deactivation Pathways in Transition Metal CatalysisPhotoredox Catalysis

IrIIIN

N

N

Photons converted into ~55 kcal/mol chemical potential energy

Typical reaction: oxidation or reduction

New paradigm for reaction development

Photoredox reaction: oxidation and reduction

Stephenson, C. R. J. et al. Chem. Sci. 2015, 6, 537.

Deactivation Pathways in Transition Metal CatalysisPhotoredox Catalysis

IrIIIN

N

N

Ir(ppy)3 (0.375 mol%)

NaHCO3, DMAblue LED

NH

Me

NH

MeCO2Et

BrO

OEt

3 equiv 85%2

Ir(ppy)3

Kinetic analysis indicates:

(1) substrate or product inhibition, or

(2) [Ir(ppy)3] is not constant due to deactivation

Stephenson, C. R. J. et al. Chem. Sci. 2015, 6, 537.

Deactivation Pathways in Transition Metal Catalysis

reference

Photoredox Catalysis

PhotoredoxCatalytic Cycle

SET

SET

IrIV

IrIII

visible light

oxidant

*IrIII

reductant

BrO

OEt

O

OEt

NH

Me

NH

MeCO2Et

NH

MeCO2Et

NH

MeCO2Et– H+

Stephenson, C. R. J. et al. Chem. Sci. 2015, 6, 537.

Deactivation Pathways in Transition Metal CatalysisPhotoredox Catalysis

IrIIIN

N

N

Ir(ppy)3 (0.375 mol%)

NaHCO3, DMAblue LED

NH

Me

NH

MeCO2Et

BrO

OEt

3 equiv 85%2

Ir(ppy)3

Kinetic analysis indicates:

(1) substrate or product inhibition, or

(2) [Ir(ppy)3] is not constant due to deactivation

Stephenson, C. R. J. et al. Chem. Sci. 2015, 6, 537.

Deactivation Pathways in Transition Metal CatalysisPhotoredox Catalysis

IrIIIN

N

N

Ir(ppy)3 (0.375 mol%)

NaHCO3, DMAblue LED

NH

Me

NH

MeCO2Et

BrO

OEt

3 equiv 85%2

Ir(ppy)3

Stephenson, C. R. J. et al. Chem. Sci. 2015, 6, 537.

Deactivation Pathways in Transition Metal CatalysisPhotoredox Catalysis

IrIIIN

N

N

Ir(ppy)3 (0.375 mol%)

NaHCO3, DMAblue LED

NH

Me

NH

MeCO2Et

BrO

OEt

3 equiv 85%2

Ir(ppy)3

mono

di

tri

tetra

penta

Stephenson, C. R. J. et al. Chem. Sci. 2015, 6, 537.

Deactivation Pathways in Transition Metal CatalysisPhotoredox Catalysis

5 (0.375 mol%)

NaHCO3, DMAblue LED

K2PtCl4

NH

Me

NH

MeCO2Et

BrO

OEt

3 equiv "reaction proceeded efficiently"2

IrIIIN

N

NBr

O

OEt

3 equiv

NaOAc 3 equiv

CH2Cl2, blue LEDIrIII

N

N

NIrIII

N

N

N

5

35% 29%

O

EtO

Stephenson, C. R. J. et al. Chem. Sci. 2015, 6, 537.

Deactivation Pathways in Transition Metal CatalysisPhotoredox Catalysis

IrIIIN

N

N

photocatalyst

NaHCO3, DMAblue LED

NH

Me

NH

MeCO2Et

BrO

OEt

3 equiv2

IrIIIN

N

N

Me

Me

Me

0.187 mol%, 18 h 0.187 mol%, 18 h72% 94%

IrIV/III = +0.77 V

IrIIIN

N

N

0.187 mol%, 48 h<50%

IrIV/III = +0.49 V

Me

Me

Me

Me

Me

Me

Meyer, T. J. J. Am. Chem. Soc. 1982, 104 , 4803.

Deactivation Pathways in Transition Metal Catalysis

reference

Photoredox Catalysis

RuII

NN

NN

N

N

Ru(bpy)32+

1CT

3CT

λmax = 453 nm

Meyer, T. J. J. Am. Chem. Soc. 1982, 104 , 4803.

Deactivation Pathways in Transition Metal Catalysis

reference

Photoredox Catalysis

RuII

NN

NN

N

N

Ru(bpy)32+

1CT

3CT

excitation

λmax = 453 nm

Meyer, T. J. J. Am. Chem. Soc. 1982, 104 , 4803. Bernhard, S. Chem. Eur. J. 2007, 13 , 8726.

Meyer, T. J. J. Am. Chem. Soc. 1982, 104 , 4803.

Deactivation Pathways in Transition Metal Catalysis

reference

Photoredox Catalysis

RuII

NN

NN

N

N

Ru(bpy)32+

1CT

3CT

excitation

ISC

λmax = 453 nm

Meyer, T. J. J. Am. Chem. Soc. 1982, 104 , 4803. Bernhard, S. Chem. Eur. J. 2007, 13 , 8726.

Meyer, T. J. J. Am. Chem. Soc. 1982, 104 , 4803.

Deactivation Pathways in Transition Metal Catalysis

reference

Photoredox Catalysis

RuII

NN

NN

N

N

Ru(bpy)32+

1CT

3CT

3d-d

excitation

ISC

thermalactivation

in absence of quencher, thermal

equilibration to 3d-d state can occur

Meyer, T. J. J. Am. Chem. Soc. 1982, 104 , 4803.

Deactivation Pathways in Transition Metal Catalysis

reference

Photoredox Catalysis

RuII

NN

NN

N

N

Ru(bpy)32+

1CT

3CT

3d-d

excitation

ISC

thermalactivation

in 3d-d state, an antibonding

metal-based orbital is populated.

significant distortion of Ru–N bonds!

Durham, B.; Caspar, J. V.; Nagle, K. J.; Meyer, T. J. J. Am. Chem. Soc. 1982, 104 , 4803.

Deactivation Pathways in Transition Metal Catalysis

reference

Photoredox Catalysis

RuII

NN

NN

N

NRuII

NN

NN N

N

RuII

NN

NN

X

N

N

RuII

NN

NN

X

X

dissociative mechanism

(no entering group dependence for Ru(bpy)2(py)22+)

*Ru(bpy)32+

3d-d state

strong-field d6

+ X– + X–

RuII

NN

NN

N

NRuII

NN

NN

X

X

+ 2X–

X– = Cl–, Br–, NCS–

Durham, B.; Caspar, J. V.; Nagle, K. J.; Meyer, T. J. J. Am. Chem. Soc. 1982, 104 , 4803.

Deactivation Pathways in Transition Metal Catalysis

reference

Photoredox Catalysis

RuII

NN

NN

N

NRuII

NN

NN N

N

RuII

NN

NN

X

N

N

RuII

NN

NN

X

X

dissociative mechanism

(no entering group dependence for Ru(bpy)2(py)22+)

*Ru(bpy)32+

3d-d statestrong-field d6

complex φp (presence of O2) φp (degassed)

[Ru(bpy)3](NCS)2

[Ru(bpy)3](Cl)2

0.039 0.068

0.062 0.100

+ X– + X–

Durham, B.; Caspar, J. V.; Nagle, K. J.; Meyer, T. J. J. Am. Chem. Soc. 1982, 104 , 4803.

Deactivation Pathways in Transition Metal Catalysis

reference

Photoredox Catalysis

RuII

NN

NN

N

N

[Ru(bpy)3]Br2

λmax = 453 nm

RuII

NN

NN

Br

Br

Ru(bpy)2Br2

λmax = 548 nm

Deactivation Pathways in Transition Metal CatalysisPhotoredox Catalysis

Ru

Ir

44

77

Electronegativity (EN)Ligand Field Stabilization Energy (LFSE)

Spin-Orbit Coupling (SO)

EN LFSE SO

increased ligand field stabilization energy makes it more difficult to

populate antibonding 3d-d state, so Ir complexes are more stable

than the corresponding Ru complexes

Tinker, L. T.; McDaniel, N. D.; Curtin, P. N.; Smith, C. K.; Ireland, M. J.; Bernhard, S. Chem. Eur. J. 2007, 13 , 8726.

Deactivation Pathways in Transition Metal CatalysisPhotoredox Catalysis

IrIII

N

N

N

N

+

Ir(ppy)2(bpy)PF6

9:3:1 MeCN:H2O:TEOA

K2PtCl4

H2H2O

IrIII

N

N

L

L

+

no d → π*N^N 3MLCT state!

Lowry, M. S.; Bernhard, S. Chem. Eur. J. 2006, 12 , 7970.

Deactivation Pathways in Transition Metal Catalysis

reference

Photoredox Catalysis

IrIII

N

N

N

N

+

Deactivation Pathways in Transition Metal Catalysis

reference

Photoredox Catalysis

IrIII

N

N

N

N

+

IrIII

N

N

L

L

+

n decomposition by loss of bpy is slow at high quencher concentration

n coordinating anions and low dielectric solvents accelerate decomposition

n high temperature results in more thermal crossing to 3d-d state

Poater, A.; Cavallo, L. Theor. Chem. Acc. 2012, 131 , 1155.

Deactivation Pathways in Transition Metal CatalysisWhy Study Catalyst Decomposition?

active for

catalysis

inactive for

catalysis

decomposition

"One of the reasons for [the] limited understanding [of catalyst deactivation] is that academic groups usually focus on the more rewarding improvement of activity and/or selectivity of a catalyst, since more or less rational strategies

can be followed, rather than investing resources to follow catalyst deactivation along unexplored pathways."