Olefin Metathesis: Catalysts and · PDF fileOlefin Metathesis: Catalysts and Catalysis...
Transcript of Olefin Metathesis: Catalysts and · PDF fileOlefin Metathesis: Catalysts and Catalysis...
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Olefin Metathesis: Catalysts and Catalysis
Matthew Cohan
and Dr. Marcetta Darensbourg
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Outline
• Introduction – What is metathesis? – Why is it important?
• Reactions – Simple synthesis reactions – Catalysis for C-C formation – Olefin metathesis
• Historical background – Nobel prizes – Mechanisms
• Catalysts types – Grubbs – Schrock
• Industrial and Synthetic Organic Applications
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Metathesis • Metathesis in the general sense is the formation of a product that has
exchanged bonds between starting materials. – A-B + C-D A-D + C-B
– Double replacement/displacement reaction.
• Metathesis in acid-base chemistry and ion exchange is well defined and simple. However, until recently, bond formation in organic reactants is difficult without the presence of catalysts.
• In the past 30 years or so industry has used olefin metathesis to form alkenes into other alkenes through a variety of mechanisms.
Spessard, G and Miessler, G. Organometallic Chemistry. 2010
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Metathesis Reactions
• Simplest are ion exchange in salts and acid-base neutralization
– KCl + NaF NaCl + KF
– H2SO4 + 2NaOH Na2SO4 + 2H2O
• More synthetically useful reactions include
– The Grignard, Diels-Alder and Wittig reactions
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Wittig Reaction
• Provides the same end goal of C-C bond formation but through a ring opening/closing pathway. A pathway that has similarity to catalytic olefin metathesis.
• Then the ring opening step forms the all important
C=C bond.
• Not Catalytic!
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Classification of Olefin Metathesis Reactions
Ring Opening Metathesis Polymerization:
Ring Closing Metathesis; Ring Opening Metathesis:
Cross Metathesis:
Ring Closing Metathesis; Ring Opening Metathesis
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from Coleman, Stanford
2
Cross Metathesis: Midsize alkenes converted to smaller/ larger alkenes
U
U
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Ring Opening Metathesis Polymerization:
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Olefin Metathesis Catalysis: The Beginning
• Transition metal-chlorides in the presence of co-catalysts were the first to be studied that afforded C-C bond formation, e.g., CH3CH2AlCl2 and WCl6
• Calderon proposed two mechanisms for the above:
transalkylation and transalkylidenation. Experiments with deuterated alkenes indicated a transalkylidenation mechanism.
• This was the start Grubbs took to find a catalyst to perform
synthetically useful reactions. Calderon, N. et al; J. Polym. Sci., Part A1 1967, 5, 2209-2217.
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A Bit of History for the Olefin Metathesis Reaction
Phillips Petroleum; 1964: Olefin “Disproportionation” (symmetry forbidden by W-H Rules). Catalysts: W(CO)6, Mo(CO)6, MoxOy/Al2O3
Goodyear Tire Company:
Calderon: Isotope distribution studies proved olefin was split at the C=C bond:
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Nobel Prizes
Historical Frame of Reference
• Previously mentioned Grignard, Diels-Alder and Wittig reactions awarded in 1912, 1950 and 1979.
• Chauvin, Grubbs and Schrock were awarded in 2005 for their work in olefin metathesis. – Preceded by decades of research
prior to 2005.
• Chauvin was the first to produce a viable mechanism for olefin metathesis.
• Schrock accidently created first stable metal carbene catalyst at MIT.
• Grubbs gave synthetic chemists an air stable and water-soluble metal carbene.
“For the development of the metathesis method in organic synthesis.”
Schrock Grubbs Chauvin
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Chauvin Mechanism 1971 Olefin Metathesis: Conversion of smaller to larger alkenes;
Begins with a Transition Metal Carbene (alkylidene).
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Other Proposed Mechanisms
Rowland Pettit, the Cyclobutane Intermediate Possibility:
Robert Grubbs, the Metallocycle Intermediate Possibility:
Robert Grubbs, updated :
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1976: From Fischer-Type Carbene, Casey discovers valuable clues to mechanism
Question to class: Synthesize the tungsten complex beginning from W(CO)6 and PhLi. What else is needed?
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Other Proposed Mechanisms: Now, getting to the truth: Fred Tebbe, 1976, the Tebbe reagent
In 1980 Grubbs uses the Tebbe Reagent and isolates:
Class: Can you analyze the Tebbe Reagent? With and without the Me2AlCl?
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Grubbs also Uses Cp2Ti=CH2 in Natural Product Synthesis
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Grubbs’ First Generation O.M. Catalyst: Synthesis
τ = 0.10
Addison’s tau value: trigonal bipyramid has τ = 1; square pyramid has τ = 0.0
Grubbs Catalyst: Structure X-ray Diffraction Analysis of Crystals
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Grubbs’ 1st generation Catalyst
16e- complex
Complex first needs to lose PCy3 proceeds through Diss. Mech.
J. Am. Chem. Soc. 1996, 118, 100-110
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Lead up to 2nd Generation Catalyst
• Let’s replace PR3 ligand with a
heterocyclic carbene and see what happens. – Increased catalytic activity, but why?
• [Ru] center prefers basic olefins over rebinding PCy3
Chem. Rev. 2010, 110, 1746–1787
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Kinetic Comparison of Phosphines and N-heterocyclic Carbenes (NHC)
Class: What is k 2/k-1?
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Grubbs’ Second Generation O.M. Catalyst
τ = 0.06
Grubbs Catalyst: Structure X-ray Diffraction Analysis of Crystals
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τ = 0.10 τ = 0.06
Grubbs’ Catalysts: Comparison of 1st and 2nd Generation Catalysts
Addison’s tau value: trigonal bipyramid has τ = 1; square pyramid has τ = 0.0
1st Generation 2nd Generation
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Class: What advantage do the large bulky ligands give? Protection for A reaction pocket.
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Schrock Catalyst: The First Alkylidene
Schrock Nobel Lecture
synthesis
mechanism
First alkylidene structure
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Schrock: Mo alkylidene selectivity
J. Am. Chem. Soc. 2009, 131, 3844; Nature 2011, 471, 461
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Hoveyda-Grubbs’ O.M. Catalyst: anchored alkylidene
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Modifications are endless:
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Ruthenium-based metathesis catalysts 3, 19, and 20.
Published in: Georgios C. Vougioukalakis; Robert H. Grubbs; Chem. Rev. 2010, 110, 1746-1787. DOI: 10.1021/cr9002424 Copyright © 2009 American Chemical Society
Modifications – even more:
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Effects of [Ru] Modification
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Catalyst Comparisons
Grubbs Catalyst(s)
• Less reactivity; greater selectivity for less bulky and or strained alkenes
• Bench stable
• Higher substrate functional group tolerance
Schrock alkylidene
• Greater reactivity with bulky and e- deficient alkenes
• Inert condition-stable
• Low substrate functional group tolerance
Nobel Chemistry Prize Lectures. Grubbs’ and Schrock’s
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Applications
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The SHOP Process Shell Higher Olefin Process
J. Chem. Educ. 1988, 65, 605
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from Coleman, Stanford
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Mind Boggling Complexities!!!
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Applications of Olefin Metathesis: Natural Products Synthesis
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Applications of Olefin Metathesis: Natural Products, Macrocycles
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Applications of Olefin Metathesis: Natural Products, RCM