NonMetathesis RutheniumCatalyzed CC Bond Formation Mechanistic Aspect

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Non-Metathesis Ruthenium-Catalyzed C-C Bond
Formation(Mechanistic Aspect)
Selected Research Topics (1)
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I. Introduction(1)

• C-C bond formation
• Important in synthetic organic chemistry
• Besides metathesis, Ru-catalyzed C-C bond
  formation is a relatively unexplored and new
  field.
• 50 cited literature after 1997.

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Introduction (2)

• Ru assumes wide range of oxidation state, from -2
  to 8. (Common oxidation states 2 to 8)
• Wide range of coordination geometries
• Wide range of catalytic processes with different
  mechanisms.
• High atom economy.

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Atom Economy

• Chemists need to measure the efficiency of
  chemical reactions in order to compare
  alternative routes to products and their
  associated economic and environmental costs.
  Percentage yield has long been used for this
  purpose, as it compares the expected product
  quantity with the actual obtained.

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Percentage yield
Calculating YieldThis compares the expected
(theoretical) mass of product with the actual
mass of product, giving the percentage figure for
the reaction. The expected mass is worked out
from the balanced equation
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Atom Economy
The concept of Atom Economy was developed by
Barry Trost of Stanford University (US), for
which he received the Presidential Green
Chemistry Challenge Award in 1998. It is a method
of expressing how efficiently a particular
reaction makes use of the reactant atoms.
This approach does not take yield into account,
and does not allow for the fact that many
real-world processes use deliberate excess of
reactants. It does, however, help in comparing
different pathways to a desired product.
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Atom Economy Calculation
The Atom Economy of this reaction is 43,
calculated using the relative formula masses.
This means that 43 of the mass of the reactants
ends up in the desired product.
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Atom Efficiency
One problem with the Atom Economy calculation is
that it does not take into account the nature of
the by-products. A reaction that generates tonnes
of carbon dioxide presents a greater
environmental problem than one that produces a
lot of water. It is sometimes helpful to consider
the economy on the basis of the elements
involved. Making maleic anhydride from benzene is
used as an example.
In this case the problem is that 33 of the
carbon available in the reactants is not
incorporated into the desired product, but
becomes carbon dioxide. Although the hydrogen and
oxygen have a much lower atom efficiency, they
are included in a much more benign product -
water.
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Organic reactions are classified as additions,
substitutions and so on. Each type by its nature
has a higher or lower atom economy.
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Initial activation

• Metallacycle formation
• Vinylidene formation
• C-H activation
• C-C activation by coordination

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II. Reactions Involving Ruthenacycle Intermediates

• 2.1. Ruthenacyclopentane

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The coupling of allenes and vinyl ketones
s-bound ruthenium-allyl complex
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• Ruthenacyclopentanes proposed as intermediates in
  the coupling of allenes and vinyl ketones to form
  1,3-dienes.
• Presumably, the steric interactions between the
  R-group and the exo-methylene group of the
  ruthenacycle (3) favor the depicted conformation,
  which leads to the formation of the E-isomer.

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CeCl3 as cocatalyst for enol activation Atom
economy
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Trapping of Ru-allyl complex
nucleophile, such as an alcoholor an amine
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The coupling of dienes and enol esters
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• The cis-geometry of the enol ester is generated
  byb-hydride elimination of Ha via a rather
  strained transition state due to the rigidity of
  the cyclopentane.
• This elimination produces allylruthenium hydrides
  25 and 26 which undergo a reductive elimination.
• It is unclear whether intermediates 25 and 26 are
  s- or p-bound allylruthenium complexes.

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An example
Excellent regioselectivity Via intermediate
24 Electronic control?
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2.2. Ruthenacyclopentene
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The coupling of alkynes and alkenes (Alder-ene
reaction)
for syn-b-hydrogen elimination difficult
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Steric factor control regioselectivity
Single regioisomer
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C-C bond at the a-carbon of the alkynoate.
The placement of an electron withdrawing group at
the b-carbon of the ruthenacycle.
26
Dominance over Diels-Alder reaction
27
Other functional group
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The coupling of alkynes and allylic alcohols
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Alkene partner no allylic proton for b-hydride
elimination
Formation of 1,3-diene, instead of
g,d-unsaturated ketone
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b-hydride elimination not possible
b-hydroxy elimination
32
An example of this process
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Formation of cyclobutene
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• A ruthenacyclopentene, 93
• b-hydrogen elimination in ruthenacyclopentane 94
  is inhibited.
• A reductive elimination to form cyclobutane 95.

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The intramolecular coupling reaction of alkenes
and alkynes
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b-hydride elimination not possible, CO
insertion, then reductive elimination
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52 cycloaddition
b-hydride elimination not possible
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52 cycloaddition
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Preparation of cycloheptane
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Preparation of cycloheptane
43
Ruthenium-catalyzed enyne metathesis to produce
vinylcyclopentenes
Ruthenacycle 120 undergoes a reductive
elimination, in preference to b-hydrogen
elimination, to produce cyclobutene 121and
regenerate the ruthenium catalyst.
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Draw the mechanism of the above reaction.
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2.3. Ruthenacyclopentadiene
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2 2 2 cycloaddition
125 cannot undergo b-hydrogen elimination or
reductive elimination.
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Coordination of oxygen to Ru metal is
important. Reaction fails with cyclopentene
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Good control of regioselectivity
Steric interaction between the R-group and the
metal center, in ruthenacycloheptatriene 127,
forces the larger group to be situated in the
R-position.
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Reactions Involving Heteroatom Additions to
Alkynes
Formation of 1,5-diketone
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• The addition of water to alkynes followed by
  trapping with enones to generate 1,5-diketones.
• A ruthenium enolate 138.
• Insertion of enone to enolate

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Intramolecular reaction
Two different products are formed. Catalytic
cycle must be different from Scheme 11.
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Intramolecular version
Ru enolate
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Additions of Halides
159 affords E vinyl halide 161
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• Complex 158, a more covalent species results in
  internal attack and a cis halometalation. The
  resulting vinyl ruthenium species (160)
  eventually generates Z vinyl halide 162.

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EZ solvent dependent
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Trapping of Ru enolate by Aldol condensation
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Addition of carboxylic acid
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• Ruthenacyclopentadiene intermediate

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Reactions Involving Additions to Ruthenium
Vinylidene Species
Oxygen nucleophiles addition of alkynes and
allyl alcohols to give b,g-unsaturated ketones
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Addition of alkynes and allyl alcohols to
give b,g-unsaturated ketones
Bond formation occurs on the more substituted
terminus of the p-allylruthenium complex
(185). intrinsic selectivity of the reductive
elimination.
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Examples
Excess allylic alcohol needed because of redox
isomerization.
isomerization suppressed.
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Rosefuran synthesis
195, a compound of interest in flavoring and
perfumery
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Using a propargylic alcohol with another pendant
alcohol, initial vinylidene formation followed by
elimination of water forming the allenylidene
197.
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As an example
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Carbon nucleophiles
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Draw mechanism
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Reactions Involving Carbametalations
fromRuthenium Vinylidene Species
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• dimerization of alkynes to form enynes

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Example
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Cumulene formation via isomerization
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The reaction is not limited to alkynes bearing
electron-withdrawing groups.
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Coupling partner 1,3-dienes with similar
mechanism
Mechanism
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Allene as coupling partner
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Coupling of olefin with alkynes to generate
1,3-dienes
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An example
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• Reactions Involving Allyl-ruthenium Intermediates

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p-Allylruthenium complexes of electrophilic nature
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Retention of configuration
Double inversion of configuration
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Additionto the more substituted terminus of the
ruthenium p-allyl.
With alkenes
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With secondary amines
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With alcohols
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Role of CO ???
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p-allylruthenium complexes of nucleophilic nature
to occur by direct insertion into the s-allyl
complex to provide 277 rather than by addition
(via allyl inversion) of the s-allyl complex to
the aldehyde.
With aldehydes
87
C-C bond formation occurs exclusively at the more
substituted carbon of the p-allylruthenium
complex.
Role of CO ???
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Carbometalation by Allyl-Ruthenium Complexes
Compared with RMg, RLi
With 1,3-butadiene
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Notably, in contrast to the addition of aldehydes
(eq 52), addition of acrylamide occurs
selectively to the less substituted terminus of
the s-allylruthenium intermediate.
With acrylamide
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syn-addition
No-syn b-hydride elimination possible
With unactivated olefins
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Reactions Involving C-H Activation

• Activation of Aromatic C-H

Compared with RMg, RLi
Aromatic C-H with alkenes or alkynes
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Directing group An ortho ketone
A vinyl silane
At the less hindered o-position
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An alkyne
syn-addition
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Imine as directing group
Regioselectivity
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Directing groups

• Ketone, imine, ester, nitriles, amines

For example,
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In the presence of CO
benzimidazole
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Activation of Vinylic C-H
Directing group X Two possible intermediates 333
or 334
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Which CH bond is activated?
103
In the presence of CO
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Activation of Aldehydic C-H
Acylruthenium complex
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• For example

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With dienes
p-allyl intermediate Regioselective C-C bond
at more substituted carbon
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Reactions Involving sp3-CH Activation
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Michael reaction 1,4-addition
R2CuLi
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Indole formation
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Reactions Initiated by Hydrometalations
An aldol reaction
An enolate
How to generate a lithium enolate?
Compare with lithium enolate!
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An example
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Dimerization of acrylonitrile
an equivalent of propionitrile
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115
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Reactions involving carbonylation
By ruthenium carbonyl complexes
118
Mechanistic aspects
119
Lactone formation

• Mechanism

A coordinating group is needed
120
Imine cyclization
121

• Examples

122

• With ethylene insertion

123
Bis-insertion of CO
124
Decarbonylation
125
Allenic alcohol
Mechanism?
126
Reactions Involving Additions of Diazo Compounds
Cyclopropanation
Carbenoid mechanism
127
A coordination mechanism.
Coordination of diazo compound and the
alkene Metathesis by products
128
Ruthenium catalysts
129
Asymmetric cyclopropanation
130
Pybox ligand
131
Addition of diazo-compounds to acetylene
1,3-dienes
Examples
132
Radical reactions

• Low-valent ruthenium complexes

Ru(III) radical
133

• Grubbs catalyst
• The addtition of chloroform to styrene

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• Intramolecular cyclization

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Mechanism
136
Asymmetric verison the e.e. is very poor. Why??
137
Trichloracetic acid derivatives
Mechanism
138
Further examples
139
Lewis Acid Catalyzed Reactions
140
the hetero-Diels-Alder reaction
Reaction between silyl enol ether and aldehyde
The oxa-ene reaction of electron-deficient
aldehydes and alkenes is catalyzed by cationic
ruthenium-salen complex
141
Ruthenium(2) catalyzes the Claisen rearrangement
of allyl vinyl ethers and diallyl ethers.
A ruthenium-catalyzed Friedel-Crafts alkylation
with alcohols and formates.
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Reactions of Vinyl Halides
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• The End