Part III. Organometallic complexes in catalysis.
Introduction and definitions.
Catalysts containing d-block metals are of immense importance to the chemical
industry. In 1990 in the US, the value of chemicals (including fuels) produced
with at least one manufacturing catalytic step was 890 billion dollars. The search
for new catalysts is one of the major driving forces behind organometallic
chemistry research.
Catalysts fall into two categories. A homogeneous catalyst is in the same phase
as the reactants (normally in solution); a heterogeneous catalyst is in a different
phase (usually solid) from the reactants.
Heterogeneous catalysts are difficult to characterize. Catalytic mechanisms are
considerably easier to study in solution where such powerful methods as NMR
can be used to assign structures and follow reaction kinetics. In this part, we are
going to look at some homogeneously catalyzed organic reactions.
1
Catalysis: introductory concepts.
A catalyst is a substance that alters the rate of a reaction without appearing in
the products. For a reversible reaction, the catalyst would alter the rate at which
the state of equilibrium is attained; it does not alter the equilibrium constant.
reactants
products
reaction coordinate
An important property of a catalyst is its selectivity, i.e. ability to lower only one
reaction pathway – to the desired product.
2
Catalytic cycle.
A catalytic cycle consists of a sequence of stoichiometric reactions (normally
reversible) that form a closed loop; the catalyst must be regenerated so that it
can participate in the cycle of reactions more than once. For example:
For efficient catalysis, the intermediates must have short “life times”.
The catalytic turnover number (TON) is the number of moles of product per mole
of catalyst; it indicates the number of catalytic cycles, e.g. one can say “after 2 h,
the TON is 2400.” The catalytic turnover frequency (TOF) is the number of moles
of product per mole of catalyst per unit time, e.g. TOF = 20 min-1.
3
Homogeneous catalysis: industrial applications.
We will discuss selected catalytic processes:
1. Alkene hydrogenation
2. Alkene hydroformylation
3. Alkene metathesis
4. Alkene polymerization.
5. Methanol carbonylation
6. C-C coupling reactions
Throughout this section, the role of coordinatively unsaturated 16- (or 14)
electron species and the ability of the metal center to change the coordination
number should be noted.
4
Alkene hydrogenation.
Although addition of H2 to a double bond is thermodynamically favorable, the
kinetic barrier is high and a catalyst is required to permit the reaction to be
carried out at a viable rate without the need for high temperature and pressure.
CH2=CH2 + H2 → C2H6
∆Gº = -101 kJ/mol
Two major pathways seem to occur with homogeneously catalyzed
hydrogenation. One involves monohydrides (MH), and the other involves
dihydrides (MH2). The MH mechanism will be considered first.
RuHCl(PPh3)3 serves usefully in the catalytic hydrogenation of alkenes, showing
very high selectivity for terminal over internal double bonds.
H2
4-vinylcyclohex-1-ene
RuHCl(PPh3)3
25 oC, 1 atm
5
The mechanism of alkene hydrogenation catalyzed by RuHCl(PPh3)3
Steps: (1) alkene addition to the unsaturated RuHCl(PPh3)3, (2) insertion or
nucleophilic attack of H− on the coordinated alkene, (3) H2 addition, (4) insertion
and elimination of the alkane; regeneration of the catalyst.
H
H
C
H
C
R
R
H
H
H
H
Ph3P
C
H
Ph3P
C
H2
18-e
PPh3
Cl
Ru H
PPh3
Ru
Cl
R
PPh3
16-e
Ph3P
H
PPh3
H
H2
R
Ph3P
C
H
H
C
H2
PPh3
Ru
PPh3
Cl
Ru
PPh3
18-e
R
Cl
PPh3
16-e
6
Wilkinson’s catalyst, RhCl(PPh3)3.
Wilkinson’s catalyst, RhCl(PPh3)3, can be easily prepared from RhCl3 and PPh3.
It is commonly used in benzene/ethanol solution in which it dissociates to some
extent; a solvent molecule (Solv) fills the vacant site:
RhCl(PPh3)3 + Solv  RhCl(Solv)(PPh3)2 + PPh3
Steps: (1) H2 addition to the
unsaturated RhCl(Solv)(PPh3)2,
(2) alkene addition, (3)
insertion or nucleophilic attack
of H− on the coordinated
alkene, (4) second insertion
and elimination of the alkane,
regeneration of the catalyst.
7
Asymmetric hydrogenation.
If hydrogenation of an alkene can lead to a chiral product, then the alkene is
prochiral. If the catalyst is also chiral, it may favor the formation of one or other
of the R- or S-enantiomers, thereby making the hydrogenation enantioselective.
Asymmetric hydrogenation can be carried out using chiral phosphines.
Enantioselective hydrogenation:
Prochiral alkene
Enantiomeric excess (ee) is defined as follows:
% ee = 100  (R-S)/(R+S), where R and S = relative quantities of R and S
enantiomers. An enantiomerically pure compound has 100% ee.
8
Asymmetric hydrogenation.
An early triumph of the application of asymmetric hydrogenation to drug
manufacture was the production of the alanine derivative L-DOPA which is used
in the treatment of Parkinson’s disease:
The anti-inflammatory drug Naproxen (active in the S-form) is prepared by
asymmetric hydrogenation. Enantiopurity is essential, since the R-enantiomer is
a liver toxin:
CO H
2
CH2
MeO
H2 Ru{(S)-BINAP}Cl2
catalyst
CO2H
C
CH2
H H
MeO
(S)-2-(2-methoxynaphthalen-6-yl)propanoic acid
"Naproxen"
9
Hydroformylation.
Hydroformylation is the conversion of alkenes to aldehydes:
RCH=CH2 + CO + H2 → RCH2CH2CHO + RCH(Me)CHO
linear
branched
The term 'hydroformylation' derived from the idea that the product resulted from
addition of formaldehyde (H2 + CO → H2CO) to the olefin. The name has stuck
even though experimental data indicate a different mechanism. A less common
but more appropriate name is hydrocarbonylation.
Hydroformylation is a homogeneously catalyzed reaction.
Historically, cobalt compounds were preferentially employed as the catalysts,
because of their low cost. Today, most new plants use rhodium complexes,
despite the higher cost of rhodium vs. cobalt:
RhH(CO)(PPh3)3 5g/$300
Co2(CO)8 500g/$290,
RhCl3 5g/$500
CoCl2 1000g/$430,
10
Mechanism of hydroformylation.
The mechanism of cobalt catalyzed hydroformylation was proposed in 1961 by
Heck and Breslow (of the Hercules Powder Company) by analogy with reactions
familiar from organometallic chemistry. Their general mechanism is still invoked,
but has proved difficult to verify in detail.
Under the conditions of the reaction (100 – 200 ºC, 100 – 400 bar) the catalytic
precursor, Co2(CO)8, reacts with H2 to give CoH(CO)4:
18-e
This complex loses CO to produce the unsaturated intermediate CoH(CO)3,
which is the catalytically active species:
16-e
11
Mechanism of hydroformylation.
It is thought that CoH(CO)3 binds the olefin:
16-e
18-e
This intermediate product undergoes an alkene (migratory) insertion into the CoH bond to give an unsaturated alkane complex:
18-e
16-e
12
Mechanism of hydroformylation.
In the presence of CO at high pressure, addition of one CO and formation of a
C-C bond (CO insertion into the Co-alkane bond) take place:
16-e
18-e
16-e
Formation of the final product is thought to occur by attack of H2
(hydrogenolysis) to yield an aldehyde and regenerate the catalyst CoH(CO)3:
13
Formation of a branched aldehyde.
A significant portion of a branched aldehyde is also formed in the cobaltcatalyzed hydroformylation. This product may result from a 2-alkylcobalt
intermediate:
1-alkylcobalt
intermediate
1
2
2
2-alkylcobalt
intermediate
1
14
Improving the selectivity of the catalyst.
The linear aldehyde is preferred for some applications, such as for the synthesis
of biodegradable detergents, and then it is desirable to suppress the
isomerization. It is found that addition of an alkylphosphine to the reaction
mixture gives much higher selectivity for the linear product. One plausible
explanation is that the replacement of CO by a bulky ligand disfavors the
formation of complexes of sterically crowded 2-alkanes:
15
Industrial hydroformylation.
Using Co2(CO)8, propene is converted with H2 and CO into a mixture of
butyraldehyde and iso-butyraldehyde. The reaction is exothermic and the heat is
removed by a tubular heat exchanger.
The n : iso butyraldehyde ratio
is between 3:1 and 4:1
16
Hydroformylation with RhH(CO)(PPh3)2.
The catalyst precursor, RhH(CO)(PPh3)3, loses a phosphine to form the 16-e
catalyst RhH(CO)(PPh3)2, which promotes hydroformylation at moderate
temperatures and 1 atm. This behavior contrasts with the cobalt carbonyl
catalyst, which typically requires 150 ºC and 250 atm.
The n:iso ratio is
as high as 20:1
17
Alkene metathesis.
The alkene metathesis reaction is one of the most original and unusual
transformations in chemistry. Yves Chauvin, Robert H. Grubbs, and Richard R.
Schrock were collectively awarded the 2005 Nobel Prize in Chemistry for their
work in catalytic alkene metathesis.
Cross metathesis (CM):
A
A
B
B
A
B
Remarkably, the strongest bond in the alkene, the C=C double bond, is broken
during the reaction. The resulting RHC= fragments are exchanged between the
alkenes that participate in the reaction. Normally, the products are statistical,
unless the reaction can be driven in some way such as by removal of a volatile
product like C2H4:
2RHC=CH2 → RHC=CHR + H2C=CH2
18
Types of catalyst.
Two types of efficient alkylidene catalysts are in common use, the Schrock and
Grubbs catalysts:
2
3
3
6 3
3 2
i
2
Of these, the Grubbs catalyst is particularly useful because it is highly tolerant of
organic functionality and is relatively air- and moisture- stable.
19
Mechanism of cross-metathesis (CM).
2RHC=CH2 → RHC=CHR + H2C=CH2
This will be considered for the RuCl2(=CHR)L2 catalyst. It is now well established
that the first step involves phosphine dissociation in solution:
RuCl2(=CHR)L2 (16-e) → RuCl2(=CHR)L (14-e) + L
Metalacyclobutane
intermediate
20
Ring-closing olefin metathesis
Ring-Closing Metathesis (RCM): is a powerful method for forming carbon-carbon double bonds
and for macrocyclizations.
• RCM) allows synthesis of 5- to 30-membered cyclic alkenes. The E/Z-selectivity depends on
the ring strain.
• The reaction can be driven to the right by the loss of ethylene.
• Ru-catalysts tolerate a variety of functional groups. The second generation Grubb's catalysts
(containing NHC) are more versatile.
Conrad et al, Org. Lett., 2002, 4, 1359.
21
Ring-closing metathesis (RCM).
22
Ring-opening metathesis polymerization (ROMP).
norbornene
Norsorex (SdF Chimie)
dicyclopentadiene
23
Alkene polymerization.
Alkene polymerization is one of the most important catalytic reactions in
commercial use. The Ziegler-Natta catalysts, for which Ziegler and Natta won
the Nobel prize in 1963, account for more than 15 million tones of polyethylene
and polypropylene annually.
The common Ziegler-Natta catalyst is TiCl4/AlEt3, which is active at 25 ºC and 1
atm; this contrasts with the severe conditions required for thermal polymerization
(200 ºC, 1000 atm). Not only are the conditions milder, but the product (HDPE,
m.p. = 135 ºC, d = 0.96 g/cm3) shows much less branching than in the thermal
method (LDPE, m.p. = 115 ºC, d = 0.91 g/cm3).
Polypropylene made by Ziegler-Natta polymerization is highly crystalline
stereoregular material – an isotactic polymer.
H
CH3
H
C
CH2
H
CH3
C
CH2
H
CH3
C
CH2
H
CH3
C
CH2
H
CH3
C
CH2
CH3
C
CH2
CH2
24
Mechanism of Ziegler-Natta polymerization.
The catalyst can be made by mixing TiCl4 and AlR3 (e.g. AlEt3 - triethylaluminum)
in heptane. The catalyst thus formed is a solid of complex constitution. It is
evident that exchange of halogen atoms and alkyl groups occurs, and that the
catalyst contains titanium alkyls. It is proposed that the active sites have
octahedral structure with a vacant site (i.e. unsaturated). (1) Ethylene is
coordinated to the metal and (2) a carbon-carbon bond is formed by insertion:
25
Mechanism of Ziegler-Natta polymerization.
Further ethylene coordination will occur, followed by insertion:
Eventually, the chain growth is terminated by β-hydrogen abstraction from the
chain:
26
Metallocene polymerization catalysts
The development of Ziegler-Natta catalysts has, since the 1980’s, included the use of
metallocenes – complexes of early transition metals with Cp ligands or ligands derived
from cyclopentadiene.
Natta JACS 1957 (79) 2975.
Breslow JACS 1957 (79) 5072.
Mechanism:
27
Breslow JACS 1959 (81) 81.
Alkene oligomerization – SHOP process.
The Shell Higher Olefins Process (SHOP) uses a nickel‐based catalyst to produce α‐
olefins for detergent manufacture. The process is complex but the following scheme
gives a simplified catalytic cycle and indicates the form in which the nickel(II) catalyst
probably operates.
T = 80 ‐ 120 °C; P = 70 ‐ 140 bar
Unlike the Ziegler‐Natta process, which aims to produce long polymers, the oligomer
stops growing after addition of ≤10 repeating units of ethylene. The fraction containing
C6 ‐ C18 olefins has commercial value (annual production > 10 Mt).
28
Carbonylation of methanol - Monsanto acetic acid process.
In the Monsanto process (1968) methanol, the primary reaction product from synthesis
gas (H2 & CO), is carbonylated to acetic acid. BP Chemicals developed a similar Ir‐
catalyzed process in 1996. Annually, 3.5 Mt of CH3COOH are produced worldwide.
Key catalytic steps:
(1) Oxidative addition of
methyl iodide to the
catalyst [RhI2(CO)2]−
(2) Insertion and
formation of an acyl
complex
(3) Coordination of CO
(4) Elimination of acetyl
iodide.
29
Catalytic C-C bond formation: cross-coupling
Pd‐catalyzed cross‐coupling of an organometal (R2[M]) with an organic electrophile
(R1X) has emerged over the past 30 years as one of the most general and selective
methods for C‐C bond formation. Contributions to coupling reactions by Ei‐ichi
Negishi and Akira Suzuki were recognized with the 2010 Nobel Prize in Chemistry.
catalyst
R1-X + R2-[M]  R1-R2 + [M]-X
R1 and R2 = alkyl, aryl, alkenyl
catalyst = PdLn (sometimes NiLn)
X = halide (Cl, Br, I), triflate (OTf)
[M] = MgX
(Kumda coupling)
[M] = ZnX, ZrX
(Negishi coupling)
[M] = SnR3
(Stille reaction)
[M] = BX2
(Suzuki reaction)
30
General mechanism of cross-coupling
14-e
14-e
R = alkyl, vinyl, aryl
31
Transmetalation
The mechanism of transmetalation is highly dependent on reaction conditions, and is a
subject of ongoing debate in the literature.
or
32
Kumada coupling, [M] = MgX
Industrial production of styrene derivatives (Hokka Chemical Industry, Japan):
Kumada coupling is the method of choice for the synthesis of sterically hindered biaryls:
NHC ligands bind strongly to
transition metals
33
Negishi coupling, [M] = ZnX
The versatile Ni or Pd catalyzed coupling of organozinc and organozirconium compounds
with various halides or triflates (aryl, vinyl, benzyl, or allyl).
catalyst
R1-X + R2-ZnX
 R1-R2 + ZnX2
R1 = alkenyl, aryl, allyl, benzyl, propargyl
R2 = alkenyl, aryl, alkynyl, alkyl, benzyl, allyl
Cataysts:
NiCl2(PPh3)2 + 2(i-Bu)2AlH 
(PPh3)2Ni(0)
Pd(PPh3)4  (PPh3)2Pd (0) + 2PPh3
Example of application:
77%
34
Stille coupling: [M] = SnR3
The successful cross-coupling in the presence of an epoxide, alcohol, carboxylic acid and
several olefin groups illustrates compatibility of the Stille reaction with common functional
groups. This example is a step in the total synthesis of (+)-Amphidinolide. Note retention of
configuration for the sp2 carbon, which is typical for Stille coupling. The main drawback is
the toxicity of stannanes.
O
Ph
O
Ph
Ph
Pd O
Ph
Pd
Ph
Ph
Pd2(dba)3
Williams, JACS 2001, 123, 765.
35
Suzuki coupling
The original Suzuki reaction was coupling of an aryl boronic acid with an aryl halide using a
palladium catalyst. Recent developments have broadened the possible applications
enormously so that the scope of the reaction partners now includes alkyls, alkenyls, and
alkynyls.
Due to the stability, ease of preparation and low toxicity of the boronic acid compounds, there
is currently widespread interest in applications of the Suzuki coupling, with new developments
and refinements being reported constantly.
A variety of organoboron reagents can be used:
36

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