olefin metathesis: fundamental chemistry applications nobel
TRANSCRIPT
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
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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,
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