Kelly Wiggins21 April 2009

“Like all sciences chemistry, is marked by magic moments. For someone fortunate enough to live such a moment, it is an instant of

intense emotion: an immense field of investigation suddenly opens up before you.” –Yves Chauvin, 2005 Nobel Laureate

Metathesis Catalysis

Outline

• History

• Mechanism

• Development of Catalysts

• Applications

• Current and Future Directions

Carbene Crash Course

Carbene - highly active organic compound in which a carbon atom has only 6 valence electrons

R2

R1Types of Stable Carbenes

* Fischer carbenes – carbene coordinated to metal with electron withdrawing ligands

* Schrock carbenes – carbene coordinated to metal with electron donating ligands

* Persistent carbenes - N-heterocyclic carbenes (NHCs)

M

R'

R

M

R'

R

N N MesMes

A New Reaction• 50’s and 60’s 1st observed by industrial chemists

– 1956 Eleuterio - DuPont - “looked like somebody took a pair of scissors, opened up cyclopentene and neatly sewed it up again.”

– 1960 Peters and Evering – Standard Oil Co.

– 1964 Banks and Bailey – Phillips Petroleum

• 1967 Calderon coins term “olefin metathesis”– One carbon of a double bond and all its substituents exchanges places with

a carbon of another double bond with all of its substituents

M. A. Rouhi, C&EN. 2002, 80(51), 34.R.H. Grubbs, Nobel Lecture, 2005.

*

MoCl6

Et3N

n

• 1967–1975 What is the mechanism?

– Caulderon’s Pairwise (Conventional) Mechanism

– Chauvin’s Metallacyclobutane

N. Calderon, E. A. Olfsead, J. P. Ward, W. A. Judy, K. W. Scott, J. Am. Chem. Soc., 1968,,90, 4133

History of Olefin Metathesis

J. L. Herisson, Y. Chauvin Makromol. Chemie, 1971, 141, 162

R.H. Grubbs, Nobel Lecture, 2005. Y. Chauvin, Nobel Lecture, 2005

• 1975 Grubbs - Deuterium Labeling

– Examined ring closing metathesis (RCM)

Mechanistic Studies

11

02

11

PairwiseChauvin

Predicted Product Ratios

R. H. Grubbs, P. L. Burk and D. D. Carr,J. Am. Chem. Soc. 1975,97,3265.T. J. Katz and R. Rothchild, J. Am. Chem. Soc. 1976,98,2519.R.H. Grubbs, Nobel Lecture, 2005

Supports Chauvin’s Mechanism!

Chauvin’s Mechanism

Yves Chauvin

Metallocycles

σ- bond metathesis

olefin insertion

olefin metathesis

alkyne insertion

alkyne metathesis

M CR2 M CR2M

CH2

CR2

CH2

M R

H H

M R

HH

M

H

R

H

M R M R M R M CR2M CR2 M

HC CH

CR2

M CR2M CR

CHHC

M

CH

CR

CH

Y. Chauvin, Nobel Lecture, 2005

Span of Olefin Metathesis

Types of Metathesis

R1R 2 R1

R 2+

**

n

**

n

R 2

R1

+

R2

R1

cross metathesis (CM) ring closing metathesis (RCM)

ring opening cross metathesis (ROCM)

acyclic diene metathesis (ADMET)ring opening metathesis polymerization (ROMP)

C.W. Bielawski, R.H. Grubbs Prog. Polym. Sci. 32 (2007) 1.R.H. Grubbs, Nobel Lecture, 2005R.R. Schrock, Nobel Lecture, 2005Y. Chauvin, Nobel Lecture, 2005

A Good ROMP Catalyst

• Well-defined

• Initiation faster than propagation

• Limits chain transfer and termination

• Soluble in organic media

• Show high stability to moisture, air, temperature, and a variety of organic functional groups

C.W. Bielawski, R.H. Grubbs Prog. Polym. Sci. 32 (2007) 1.

ROMP Mechanism

C.W. Bielawski, R.H. Grubbs Prog. Polym. Sci. 32 (2007) 1.

Chain Transfer in ROMP

C.W. Bielawski, R.H. Grubbs Prog. Polym. Sci. 32 (2007) 1.

Moving toward a Catalyst

• Katz -1976 “First” well-defined catalyst

•Little MW control

•PDI > 1.85R=Ph or OMe

Katz suggested that the presence of a carbene on the catalyst

would facilitate reactivity.

Thomas J. Katz

C.W. Bielawski, R.H. Grubbs Prog. Polym. Sci. 32 (2007) 1.Rouhi, M. A. C&EN. 2002, 80(51), 34.

Towards an Efficient Catalyst

Titanium– isolable metallocyclobutane

– catalyzes ROMP of norobornene with good MW control, PDI ~ 1.2

– reactive with heteroatoms

Tantalum • higher activity than Titanium

• reactive with heteroatoms

• catalyst tailoring– the bulky, electron rich aryloxides

decreased side reactions

– PDI ~ 1.1 with bulky as opposed to PDI ~ 1.6 with less bulky groups for ROMP of norbornene

Ar = 2,6-diisopropylbenzene

Ar = 2,4,6-triisopropyl benzene

C.W. Bielawski, R.H. Grubbs Prog. Polym. Sci. 32 (2007) 1.R.H. Grubbs, Nobel Lecture, 2005R.R. Schrock, Nobel Lecture, 2005

Tungsten Catalysts

Basset’s Tungsten Catalyst

•wider functional group tolerance (acetates, nitriles, anhydrides)

•bulky alkoxide ligands show stereoselectivity

•high activity, increased side reactions

Schrock’s Imido-alkoxy Catalyst

•alkoxides varied to modulate activity

•limited functional group tolerance

C.W. Bielawski, R.H. Grubbs Prog. Polym. Sci. 32 (2007) 1.R.R. Schrock, Nobel Lecture, 2005

Schrock’s Catalyst

•Molybdenum alkylidenes, well-defined

•highly active

•good functional group tolerance

•ester, amide, imide, ketal, ether, cyano, trifluoromethyl,

and primary halogens

•must be used in inert conditions, no water

•stereochemical control through chiral alkoxy ligands

Molybdenum Catalysts

isotactic polymer

Richard R. Schrock

C.W. Bielawski, R.H. Grubbs Prog. Polym. Sci. 32 (2007) 1.R.R. Schrock, Nobel Lecture, 2005

Ruthenium Catalysts

Robert H. Grubbs

First Generation

Second Generation

Grubb’s Catalysts

•highly stable

•minimal side reactions

•e- donating lingands

•readily initiated benzylidine moiety

•increased functional group tolerance (Schrock tolerance + water, alcohols, acids)

•Selective to alkyl substituted double bonds

•ROMP highly strained rings

• σ donating NHC ligand increases electron density on the metal

•reacts with e- deficient double bonds

•more reactive, faster phosphinedissociation

•more stable, bench top ROMP

C.W. Bielawski, R.H. Grubbs Prog. Polym. Sci. 32 (2007) 1.R.H. Grubbs, Nobel Lecture, 2005

Why should we care?

RCM Applications in Pharmaceuticals

R.H. Grubbs, Nobel Lecture, 2005

But . . .we like polymers

Crosslink

R.H. Grubbs, Nobel Lecture, 2005

Dicyclopentadiene (DCPD)

A ROMP in Water!

Water Soluble Grubb’s Catalysts

•incorporation of charged ligands allows for water solubility

•HCl promotes initiation and prevents decomposition

•PDI < 1.24 for homopolymers

C.W. Bielawski, R.H. Grubbs Prog. Polym. Sci. 32 (2007) 1.R.H. Grubbs, Nobel Lecture, 2005

Summary

Mechanism of Olefin Metathesis

Grubb’s First

Generation

Grubb’s Second

Generation

Schrock’s

Catalyst

Olefin Metathesis Catalysts

most reactive

least stable

least tolerant

$ 491/ gram

least reactive

moderately stable

very tolerant

$101/gram

highly reactive

very stable

very tolerant

$316/gram

M CR2M CR2

M

CH2

CR2

CH2

The Nobel Laureates

Yves Chauvin Institut Français du PétroleRueil-Malmaison, France

Robert H. Grubbs Richard R. Schrock Caltech

Pasadena, CAMIT

Cambridge, MA

2005 Nobel Prize in Chemistry

“for the development of the metathesis method in organic synthesis”

Y. Chauvin, Nobel Lecture, 2005 R.H. Grubbs, Nobel Lecture, 2005 R.R. Schrock, Nobel Lecture, 2005

New and Future Directions

• Development of new catalysts– late transition metals with highly donating ligands

– ideal catalyst reacts with all cyclic olefins regardless of functionality

– “universal catalyst”

• Polymerize new monomers– tri- and tetra-substituted olefins evidence of which has been seen in RCM

• Control – structure relates to function

N NMesMes

N

O NN N PhMesMesN N MesMes

N NN N

Development of New Ligands

N

N

Fc

Fc

N

N

Fc

Fc

N

N

Ph

Ph

FcN

N

Fc

CH3

N N MesMes

OO

Fe

N

N

R

R

Development of Redox Active Ligands

E. Rosen, J. Kamplain, D. Sung, D. Varnado, C.W. Beilawski. Manuscript in preparation.C.W. Bielawski, R.H. Grubbs Prog. Polym. Sci. 32 (2007) 1.

Schrock Carbene•triplet carbene•high oxidation states •early transition metals•non pi-acceptor ligands on metal •non pi-donor substituents on carbene

Fischer Carbene•singlet carbene•low oxidation state metals •middle and late transition metals •pi-electron acceptor ligands on metal•pi-donor substituents on carbene (alkoxy and alkylated amino)

M

R'

R

M

R'

R

Carbenes

Grubb’s Idea

Ruthenium

•low oxophilicity – good functional group tolerance

•readily bonds to carbon

•RuCl3 showed increased activity in protic media

•extraordinary tolerance to polar functionality