olefin metathesis: fundamental chemistry applications nobel

Olefin Metathesis:Fundamental Chemistry

Applications

NCKUDiscussion

June 25, 2008

Nobel

Olefin Metathesis

Rearrangement of olefins (C=C bonds)by catalyst.

C C

H

H CH3

H

C

C

HH

H H

C C

H

H CH3

H

+CCH3H

CCH3H

+

Olefin

MetathesisCatalyst

A compound or substance that promotes achemical reaction

• Metal complexes• Enzyme• Acid or base

Catalysis

Energetics of Catalysis

CatalyticPath

A B

E

2H2 + O2 H2O

Olefin Metathesis Mechanism

RHC=CHR RHC=CHR RHC CHR+ 2[M] CHR

[M] CHRRHC=CHR

[M] CHR

[M]

RHC CHR

CHR

RHC CHR

[M]

RHC CHR

CHR

RHC=CHR

RHC=CHR

RHC=CHR

[M] CHR

LnM=CHR

THE METAL-CARBENE HAS FORMED

M C*

METATHESIS ON THE WAY

MC*

C1C1

C2C2

METATHESIS ON THE WAY

C1C1

MC2

C1C2

C1C2

METATHESIS ON THE WAY

M

C1

C1C2

The Ruthenium Story

Synthesis of an IonophoreO

O OO

n

O

O

O

RuCl3

RuCl3

Benzene/Ethanol n

F. W. Michelotti, W. P. Keaveney, J. Poly. Sci., Part A, 1965, 895

O

OO

nTi, W based Catalysts

No Polymer

Ruthenium Catalyst Synthesis

Ill defined, highly active, little initiation

Well defined, good activity, 100mg/week

!

Functional Groups

Dumb

Smart

Metal-Centered-Functional Group

N N

Ru

PCy3

Cl

Cl

Ph

Olefins

Acids

Alcohols, water

Aldehydes

Ketones

Esters, Amides

Activity Similar to Moand Retains tolerance

Uses and ApplicationsResulting from Stable,

Tolerant Catalysts

RuR

D

D1

Cl

ClD=2 electron donor

General Catalyst Structure

Carbon-Carbon Double BondForming Reactions

CMR1

R2R1

R2

n

RCM

n

ROMP

n

ADMET

n

Materials

Unanticipated Applications!

Polymer Synthesis

Mechanical PropertiesChemical Function

What are Polymers?

Large molecules made by connectingsmall molecules (called monomers).

Size Does Matter!Monomers - Gas or liquid - High Mobility

Oligomers (small polymers) - Viscous liquid - Reduced mobility

Polymers - Gels or solids - Little or no mobility

Polyethylene: The Simplest Polymer

C C

H

H H

HC C

HH

H H

C C

HH

H H

C C

HH

H H

C C C

HH

H H

C

H

H

H

H

Ethylene Repeating Unit

Multi-use polymer

Properties depend on how polymer is synthesized and processed.

Dicyclopentadiene-Thermoset Polymer

PolyDCPD-9mm Ballistic Protection

Products Made With DCPDROMP

Sports EquipmentTruck Parts

Consumer products

www.plastictechnology.combaseball.eastonsports.com

[Ru] cat.n

DCPD poly(DCPD)

2006 Combine (8 Year Program)

Ring Closing Metathesis

RCM

O

OEt

O

EtO

O

OEt

O

EtO

+ CH2=CH2

Ring Closing Metathesis withWell Defined Catalysts

(CH2)X

O Ph

O Ph

SiMePh

O

O

93%

92%

71%

+CH2=CH2

+CH2=CH2

+CH2=CH2

MoPh

Me

Me

N

i-Pri-Pr

RfO

RfO

G. C. Fu and R. H. Grubbs, J. Am. Chem. Soc., 1992, 114, 5426-5427. J. Am. Chem. Soc. 1992, 114

(18), 7324-7325. , J. Am. Chem. Soc., 1993, 115, 3800-3801

G. C. Fu, S. T. Nguyen, and R. H. Grubbs, J. Am. Chem. Soc. 1993, 115, 9856-9857.

Ru Ph

Ph

PCy3

PCy3

Cl

Cl

Pharmaceutical Applications

Drugs

Boehringer IngelheimHepatitis C Drugs

15

T. Nicola, M. Brenner, K. Donsbach, and P. Kreye, Organic Process and Development, 2005, 27.

HCV Serine Protease InhibitorBoehringer Ingelheim’s BILN 2061Phase II Clinical Trials in US and Europe

N

HN

O

O

O

NO

OO

O

S BrO

O

N

HN

O

O

O

NO

OO

O

S BrO

O

Ru

toluene

N

HN

O

OH

O

NO

OO

O

N

S

N

N

MeO

400 kg.

GSK Osteoporosis Drug

Protease Inhibitor of cathepsin K

NO

R1 O

NO

R1 O

NO

R1 OO

NNHR

O

R2

R1= amide, sulfonamide, peptide

R2 = aminoacid side chain

The Prince the Two Princesses

GREEN CHEMISTRY

Environmentally friendly chemistry

Green Chemistry• Starting material

– Renewable– Simple structures

• Processing– Minimize number of steps– Few/no by products– No/little solvents (Water)– Low energy input

• Products– Replace polluting materials– Replace petroleum based material

A Codevelopment Program for theConversion ofSeed Oils to

Value added Chemical

Cargill- Materia- Caltech-DOEReplace petroleum based products

with those from renewable resourcesSeed oils (corn and soy beans) are highly unsaturated (many double bonds)

and can be modified by Olefin Metathesis

to value added functional molecules

Cargill anticipates that it will have commercial sales in 2006 of several million pounds of a proprietary Ruthenium-metathesis based product derived from a renewable resource that will replace a petroleum-based material.

Cargill is planning to produce several million pounds of a proprietary metathesisproduct derived from a renewable resource that will replace a petroleum-based product next year.

Cargill is planning to produce several million pounds of a Cargill proprietary metathesis based product derived from a renewableResource that will replace a petroleum-based product next year.

Oleic Acid to Value Added Chemicals

RO

O

RO

O

RO

O

+

+

H2C CH2 Ru Catalyst

RO

O

R = H or Me

Ru Catalyst

Oleic Acid

Use in Polyolefins and synthetic oils

Use in coatings

Polyesters

Linear hydrocarbon

No Solvents

EthenolysisHomometathesis

OO

OO

OO

OO

OO

OO

OO

OO

OO

OO

OO

OO

OO

OO

OO

OO

OO

OO

Self-metathesis

Hydrogenation

Hydrogenation

Metathesis ModifiedSoybean Oil

Soybean oilHydrogenatedSoybean Oil

Metathesis DimerHydrogenated

Metathesis Dimer

Metathesis Trimer

Metathesis Oligomers

Hydrogenation

Hydrogenation

HydrogenatedMetathesis Trimer

HydrogenatedMetathesis Oligomers

Traditional NatureWaxTM products

Metathesis modified renewable oil waxes havebeen successfully introduced into compressionand extrusion products

• Cargill’s metathesismodified renewableoil wax blends

– Bring enhancedfragrancecapacity andclean burning

– Plusprocessability

Statistical Distribution of CM Products

Insect Pheromones

Omnivorous Leafroller(Platynota stultana)is a pest of apples,

grapes, pears,peaches andnectarines.

Environmentally friendly alternatives to pesticides that utilizemating disruption as a means of controlling insect populations

Peach Twig Borer(Anarsia lineatella)is a pest of peaches,

plums, nectarinesand almonds.

Pheromones in Action

Pheromones in Action

Chemical Structure ofPheromones of Interest

Fgm

n

Fg = Carboxylic Acid Derivative

OAc

OH

PTB Pheromone(Peach Twig Borer Pheromone)

5-Decenyl Acetate(85:15 E:Z ratio)

Peach Twig Borer(Anarsia lineatella)is a pest of peaches,

plums, nectarinesand almonds.

Pheromone by Cross MetathesisOAc

AcOOAc

+

OAc

OAc+

85%

15%

Ru Cat Ru Cat

Ru Cat

50%

-CH2=CH2 -CH2=CH2

PHEROMONE for Peach Twig BorerUsed in Mating Disruption

Catalyst removed with P(CH2OH)3

No Solvents Used

OAc OH+83% 17%

Bugs

OLR is a pest of apples, grapes, pears, peaches, etc. The pheromone, 11-tetradecenyl acetate, can be obtained with the desired trans:cis ratio of82:18 by cross-metathesis of 11-eicosenyl acetate with 3‑hexene.

82:18 E:Z-11-Tetradecenyl Acetate

R.L. Pederson et al. (2002) Adv. Synth. Catal. 344, 728-735.Pederson and Grubbs US 6,219,019

Jojoba plant

Production of the OmnivorousLeafroller (OLR) pheromone

OAc

+

OAc

200ppm 6275°C

excess

OLR PheromoneE and Z-11-Tetradecenyl Acetate

Traditional Synthetic Methods

14 Steps15% overall yield

Metathesis Technology

6 Steps Starting withCommon Seed Oils50% Overall Yield

75% Reduction inproduction costs

OAc

OAc

(Omnivorous Leafroller Pheromone)

Jojoba plantMateria

CH3O

O

9

6 : 1 E:Z ratio

1) Transesterify2) Metathesis3) vacuum distillation

OO

OH

Methyl 5-Hexadecenoate

(+/-) 6-Hydroxy-5-Hexadecanolide

OO

OAc

(+/-) 6-Acetoxy-5-Hexadecanolide

Acetylate

O

O

O

O

O

O

l

m

n

(erythro:threo is >10:1)

l,m,n is 13 or 15

Meadowfoam Oil

Synthesis of MOP

Pederson and Grubbs US 6,219,019

Meadowfoam

Mosquito Oviposition Pheromone-MOP

Group 2008

Jim HeathMike Phelps

Choel ChungJean LiChris Daeffler

Paul ClarkMike Page

John MatsonRon WalkerIrina GorodetskayaYan Xia

ROMP PolymersNew Catalysts and Applications

NSF, NIH, Navy, Materia, Amgen, Cargill

Joseph SamecDaryl AllenGeorgios Vougioukalakis

Donde Anderson, Erin Guidry, Jason Jordan,Soon Hong, Katie Campbell, Chris Douglas, Andrew Hejl,Takashi Koike, Jacob Berlin,Connie Hou, Anna Wenzel, Al Nelson, Masao Yanagawa, Greg Beutner, Tim Funk, Tobias Ritter,Christie Morrill, Brian, Connell, Andrew Waltman, Paula Diaconescu, Diego Benitez, Emmanuelle Despagnet, Anatoly Chlenov, Arnab Chatterjee,

Kevin KuhnIan StewartMike MalarekJ. B. BourgPatricio RomeroMatt Whited

Recently Departed

Materia- M. Giardello, M. Trimmer, Y. SchrodiConsultants- Dan O'Leary, Julie Kornfield