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First Course Handout (FCH); Course-CSO201A: Organic Chemistry: Fundamentals and Applications,
Department of Chemistry, IIT Kanpur
Instructors: Prof. Manas K. Ghorai and Dr. Ramkrishna Sarkar
1. Course Content:
Olefin Metathesis: Catalysts and Catalysis (8 L): Introduction, Olefin metathesis, Catalysts types (Schrock, Grubbs-I, Grubbs-II),
Ring closing metathesis (RCM), Ring opening metathesis (ROMP), ene-yne metathesis, Industrial and Organic Synthesis
applications
Transition metal catalysed cross coupling reactions (8 L): Palladium based reactions such as Heck, Stille, Suzuki, Sonogashira,
Buchwald-Hartwig couplings; Tsuji-Trost C-C bond formations; Mechanism and stereochemistry of various coupling reactions.
Industrial and Organic Synthesis applications
Visible Light Photocatalysis (8L): Introduction, An Overview of the Physical and Photophysical Properties of catalysts, Visible-
Light-Mediated Free Radical Synthesis, Atom Transfer Radical Addition using Photoredox Catalysis, Metal-Free Photo (redox)
Catalysis, Application of Visible-Light Photocatalysis in the Synthesis of Natural Products
Click chemistry (8L): Introduction, Mechanistic and synthetic perspectives, Various types of click chemistry, Applications of click
chemistry in the area of peptide, and nucleic acids, drug discovery, and development, Azide–alkyne click reaction in polymer
science 2
First Course Handout (FCH); Course-CSO201A
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First Course Handout (FCH); Course-CSO201A
6) Evaluation:
Final Exam: 50%
Mid Semester: 35%
One quiz (surprise/announced) /assignment: 15%
8) Grading Policy:
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Olefin Metathesis
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Metathesis
q A chemical reaction between two compounds in which parts are interchanged and form two new
compounds. It is also called a double displacement reaction
Ethylene
q Alkenes are also called olefins (oil-forming) as alkenes (smaller) form oily products when they are reacted with
chlorine or bromine
q Robert H. Grubbs, Richard R. Schrock, and Yves Chauvin were awarded the 2005 Nobel Prize in Chemistry for
their contribution to olefin metathesis
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https://www.nobelprize.org/prizes/chemistry/2005/summary/
Classifications of metathesis reactions
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9.1.2023
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Olefin Metathesis: The Beginning
q In 1964, R. L. Banks and G. C. Bailey at Phillips Petroleum Company described olefin disproportionation converting propylene
to an equal mixture of ethylene and 2-butene.
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Propylene Ethylene 2-butene
q In 1967, Nissim Calderon examined the disproportionation reaction of 2-pentene and coined the term “olefin metathesis”.
Observed
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J. Am. Chem. Soc. 1968, 90, 15, 4133–4140
Chauvin’s mechanism
cyclopentene 2-pentene
q Chauvin (in 1971) examined the reaction of cyclopentene and 2-pentene with catalyst tungsten(VI) oxytetrachloride and
tetrabutyltin
q The three principal products C9, C10 and C11 were found in a 1:2:1 regardless of conversion.
Metallacycle
intermediate
q Chauvin proposed a four-membered metallacycle intermediate that explains the statistical distribution of products.
Die Makromolekulare Chemie. 141 (1): 161–176. doi:10.1002/macp.1971.021410112 13
Chauvin’s mechanism
Initiation R1
Same starting (Catalyst)
materials +
R2
Propagation
Overall mechanism
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Statistical distribution
Cross-metathesis-1 Cross-metathesis-2
Self-metathesis-1 Self-metathesis-2
Overall reaction
Product ratio
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Chemical reaction and Activation energy
A B ΔG=ΔH−TΔS ΔG = change in Gibbs free energy of
the reaction; ΔH = change in enthalpy
(Reactant) (Product) ΔG < 0 spontaneous reaction ΔS = change in entropy
ΔG> 0 nonspontaneous.
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Catalyst in Olefin metathesis
Catalyst
(Nissim Calderon)
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11.1.2023
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Chauvin’s mechanism
(Catalyst)
Initiation
Dance of the “catalyst pair” and the “alkene pair”
Propagation
The “catalyst pair” and the A united ring dance with one of leave their old partners and
“alkene pair” dance their hand holding onto the dance on with their new ones
previous partner
https://www.nobelprize.org/uploads/2018/06/popular-chemistryprize2005.pdf
2+ 2 cyclo addition of Metallacycle Metathesis product
alkene and metal intermediate
alkylidene 20
Chauvin’s mechanism in details
Initiation
1, 2 3, 4
Metallacycle New metal
intermediate alkylidene
Catalyst
1 2 3 4
2 3 4
1, 2 Metallacycle
3, 4
Product
intermediate
1 2 3 4
2 3 4
Tunable
reactivity Stable
Catalyst
requirements
Metathesis in the presence of other functional
Tolerance of groups. The compound is important for anti-
Well-defined functional groups cancer activities.
ü Schrock catalyst,
ü Grubbs catalyst
Molybdenum-based Schrock catalysts Grubbs Catalyst® 1st Generation 23
Schrock catalyst
q In 1990, Schrock and co-workers reported the construction of a group of very active, well-defined molybdenum,
tungsten, and tantalum catalysts
q Schrock catalysts are more active but sensitive to oxygen and moisture
q Reactivity and selectivity of metathesis reaction can be tuned by varying the ligands
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Metathesis using Schrock catalyst
Disadvantages of Schrock’s
catalyst
1.Poor functional group tolerance
2.This catalyst is very sensitive to
With a Schrock catalyst modified with a BINOL ligand, in a O2 and moisture.
norbornadiene ROMP leading to highly
, stereoregular cis,
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isotactic polymer.
E and Z selectivity
q The inherent reversibility of olefin metathesis (products can re-enter the catalytic cycle) and the higher reactivity of Z alkenes
(versus E isomers) causes E forms predominantly 26
Z selectivity in cross metathesis using Schrock catalyst
q The free rotation of large monodentate aryloxide causes the incoming alkene to be oriented such that its substituent (R2) is
situated syn to that of the alkylidene (R1).
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Anti-tumor agent KRN7000
q Z-Selective CM thus provides access to shorted route (9 steps than 14 otherwise) is the shortest synthesis of route KRN7000
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Nature, 2011, vol-471, 461-466 doi:10.1038/nature09957
12.01.2023
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Grubbs catalyst
(Catalyst)
q Grubbs catalysts are a series of ruthenium-based transition metal carbene complexes, less reactive than Schrock catalyst
But more selective
q Grubbs catalysts tolerate many functional groups, are air-tolerant and are compatible with a wide range of solvents
The first well defined ruthenium catalyst developed by Grubbs. It was prepared from
RuCl2(PPh3)4 and diphenylcyclopropene.
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SonBinh T. Nguyen, Lynda K. Johnson, and Robert H. Grubbs* J. Am. Chem. Soc. 1992, 114, 10, 3974–3975
Grubbs catalyst
q Grubbs’ catalysts are used in a daily basis as (standard) catalysts for metathesis
q The first-generation Grubbs catalyst was the first well-defined Ru-based catalyst. It is also important as a
precursor to all other Grubbs-type catalysts
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Grubbs 2nd and 3rd generation catalyst
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Polymer and block copolymer
Monomer
Dimer
A
Trimer
Tetramer Polyethylene (PE)
Polymer (homopolymer)
Polymerization B
2,3-Dideuterio-norbornene (DDNB)
Catalyst
Polynorbornene (PNB) ROMP
(homopolymer) PNB-b-PDDNB
Grubbs Catalyst
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SonBinh T. Nguyen, Lynda K. Johnson, and Robert H. Grubbs* J. Am. Chem. Soc. 1992, 114, 10, 3974–3975
Cross metathesis (CM) and reactivity of olefins
The desired product will be a maximum yield of 50%, (homometathesis), 25% yield (each)
q The reactivity of one of the partners can be controlled by either electronic or steric factors in favor of CM
q Electron-rich olefins exhibit higher reactivity in metathesis
q One olefin can be added in excess
Grubbs catalyst
only One double
bond reacts
q The Self-metathesis products are present in the reaction mixture and can be also converted into the expected CM
Allylic alcohol
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Isomerization of olefin in metathesis
q C–C double bond could undergo isomerization (migration)
q Participation of the isomerized products in the metathesis can results in a large number of by-products