Organometallic Reactions

and Homogeneous Catalysis

• Ref: Weller, p.636
• Oxidative addition: [IrCl(CO)L2], PdL4 (L = PPh3)
• Reductive elimination: C-C and C-H elimination
• Migratory insertion: M(CO)R, M(olefin)H/R
migration vs. insertion pathway
• Homogeneous vs. heterogeneous catalysis
• Rh-catalyzed hydrogenation of olefins
• Co-catalyzed hydroformylation of olefins
• Monsanto process
• Suzuki Coupling
• CH Activation

1
 Why we learn organometallic chemistry?
Haber−Bosch process

Key to food supply

Nature: nitrogenase enzyme

The Nobel Prize in
Chemistry 1918
and 1931

2
Why we learn organometallic chemistry?

One of the most widely used coupling reaction in drug synthesis

The Nobel Prize in

Chemistry 2010

3
 Oxidative Addition

Oxidative Addition
(i) •Coordination no.  2
n A •Oxidation no.  2
M + A-B n+2
M B
Reductive Elimination

(ii)
A •C.N.  1, O.N.  2
n OA n+2
M + A-B M +B

Chemistry focuses on electrons

4
 Requirements for oxidative addition:
(i) The complex is coordinately unsaturated: 18 e rule
(ii) Higher oxidation states (n + 2 or n+1) of metal are
accessible

Examples:
Na[Mn(CO)5] + MeI → [Mn(CO)5Me] + NaI

Mn(-I), TBP Mn(I), Oct

5
Example: Vaska compound Ir(CO)Cl(PPh3)2

A B B B
OC PR3
Ir Ir or Ir
R3P X A
A
Vaska compound
Ir(III) d6
Ir(I), d8 octahedral
square planar
Different isomers are possible
A-B = H-H, H3C-I, H-X etc. • A and B can be cis or trans
• Two PR3 can be cis or trans

6
 Examples of oxidative addition of Vaska compound

Electronic: A-B electron poor electron-withdrawing => strong backbonding

Steric: A-B less bulky Metallocyclopropene
(cf. metallocyclopropane for olefin complex)

Strong backbonding=> IrIII

[Ir] = Ir(PPh3)2(CO)Cl
Different isomers are
possible

Ir(III) peroxo
O22-: peroxide
Silyl hydride
complex

SnCl3-:
anionic ligand
(stannyl)
acyl
7
Expect: Electron-rich complexes undergo OA more easily

e.g. R' X' R'

OC PR3 X'
Ir Ir
R3P X

Rate of O.A. R: Et > Ph > C6H4F

bigger than Rh,
X : I > Br > Cl
- Interection
between Ir
 (ii) Which one, (1) [Ir(CO)Cl(PPh3)2] or (2) wI
reacher VE is

[Rh(CO)Cl(PPh3)2], undergoes OA with H2 more easily?

reactive
less electronegative, more

5:56:58 PM 8
Oxidative addition with 18e complexes

PPh3
Ar-X
Ph3P Pd X
Pd PPh
Ph3P 3 Ar PPh3
PPh3
18e, Pd(0) e.g. Br 16e, Pd(II)

- PPh3

"Pd(PPh3)2"
14e

9
 Reductive Elimination
(i) C-H bond formation
e.g. cis-PtIV(H)(CH3)2(I)(PEt3)2 → cis-PtII(PEt3)2(Me)(I) + H-CH3

(ii) C-C bond formation

e.g. fac-[PdIV(Me)3(PPh3)2I] → trans-[PdII(PPh3)2(Me)I] + CH3-CH3

cis-[NiII(Ar)(CH3)(PEt3)2] ⎯→ "Ni0(PEt3)2" + Ar–CH3 (Ar = aryl)

*Pd and Ni complexes are catalysts for C-C bond forming

reactions

10
(iii) C-N/C-O bond formation

C-N/C-O bond R.E. is challenging compared with C-C R.E. Why?

11
• Necessary condition for RE: the two leaving ligands
must be CIS to each other

CH3
RE
Ph3P Pd CH3 H3C CH3 + Pd(0)
PPh3
cis

Ph CH3
Ph No RE
Ph P Pd P
H3C Ph

12
• Expect: electron deficient complexes undergo RE
more readily.

• Cationic complexes undergo RE more easily than

their neutral analogues

RE rate: [Fe(bpy)Et2]+ > [Fe(bpy)Et2]

 (ii) Which one, A or B, undergoes RE more easily?

A
B
13
Science 2015, 347, 1218–1220.
Metal-catalyzed cross-coupling of RX with Grignard reagents (RMgX)

cat. M(0) or M(II)

RMgX + R'X' R-R' M = Ni or Pd

M(II) R'MgX
(reducing agent)
R
R-X II
M(0) M X
O.A.

R'MgX (Grignard)
R-R' R
R.E. (Alkylating agent) (transmetalation)
M R'

Kumada coupling 14
 Exercise
• Propose mechanism for the following reaction
[Pt(PPh3)4] + 2HCl → Pt(PPh3)2Cl2
What is the by-product of the above reaction?
H
2PPh3 PPh3
Pt(PPhe)y
-

HG
c
Pt(PPhs)c 7
Pt
hu/heating 0. A
U
PPh3

0. A
HC
V

H
U
- PPh3 H I PPhs
-

H2
Pt < Pt
R. E. U
U I
PPh3 PPhs
H

15
 Exercise
• Rank the O.A. rate of the following substrates with
Pd(PPh3)4. I
3
2

• Rank the R.E. rate of the following compounds.

3 Y 2 I

16
 Summary

O.A. R.E.
TM Electron rich Electron poor
A-B reagent Electron poor Electron rich

17
 Migratory Insertion (migration)

•Coordination no.
•Oxidation no.

Examples (a) CO insertion

R L
L O
M CO M C R
Alkyl Acyl

18
1,2-insertion: insertion with
h2-ligand such as alkene
results in the formation of
h1-ligand without change in metal
oxidation state

19
Mechanism

A A L A
L
M B M B M B
Migratory insertion is easy if
(i) M-A bond is weak
(ii) L is a strong nucleophile

Therefore, rate of MI with PPh3 (to give CpM(COMe)(PPh3)(CO)2)

CpCr(CO)3Me > CpMo(CO)3Me > CpW(CO)3Me

Metal-carbon bond strength, D(M-C): Cr < Mo < W

TM:M-C bond
strength increases down the
group

Main group:M-C decreases down the

group 20
Two possible pathways

21
Examples:
H3C Ph3P O
PPh3 C CH
OC CO OC
Mn Mn 3
OC CO OC CO
CO CO

Note. Another optical

isomer is formed for
Insertion pathway

PPh3
H PPh3
H Mo
Mo CH2
C H
H C CH3
H

22
 De-insertion (elimination)
•Microscopic reverse of migratory insertion
•Should proceed by the same mechanism

De-insertion
e.g. [Mn(CO)5(COMe)] → [Mn(CO)5Me] + CO (decarbonylation)

LnM-CH2CH2R → LnM-H + CH2=CHR (b-H elimination)

ALKYL HYDRIDE (will be discussed later)

23
 Consider the decarbonylation of Mn(CO)4(13CO)[C(O)Me]

(i) For CO de-insertion pathway

O Me
axial C
equatorial CH3
OC *CO
OC CO
OC
Mn
CO Mn 25% probability
O Me OC CO
CO
C CO
OC *CO
Mn
OC CO
CO
*C = C-13
O Me
CH3
C OC *CO
OC *CO
Mn
Mn 75% prob.
OC CO
OC CO
CO CO

➢Expect: 25% unlabeled and 75% C-13 labeled cis product

24
 (ii) For methyl migration pathway

O Me
C CO
OC *CO OC Me
Mn Mn 25% prob.
OC CO
CO OC CO
O Me CO
C Me O
OC *CO CO
C Me *CO
OC
Mn
CO
OC *CO Mn
50% prob.
Mn
CO OC CO
OC CO
CO CO
*C = C-13
cis
Me O CO
C OC *CO
OC *CO
Me
Mn
CO
25% prob.
Mn
CO
OC CO
CO trans

➢Expect: 25% unlabeled, 50% labeled cis, 25% labeled trans

25
➢ The observed distribution of cis to trans product is about 2 to 1.

➢ Methyl migration pathway is involved in both

the decarbonylation of Mn(CO)5[C(O)Me]

and its microscopic reverse, i.e. migratory insertion,

of Mn(CO)5Me with CO.

26
Applications of Na2[Fe(CO)4] (Collman’s reagent) in organic synthesis

e.g. synthesis of carbonyl compounds

27
 Homogeneous Catalysis

Homogeneous catalysis Heterogeneous catalysis

• Soluble catalyst Solids, metal, oxides

• Same phase Different phase
• Difficult product separation Easy separation
• Mild conditions High temp, pressure
• More selective low selectivity
• Easy to study mech. Difficult
• FINE CHEMICALS BULK CHEMICALS
e.g. drugs

28
 Catalysis
catalyst
Substrate + reactant Product
(S) (R) (C) (P)

Why Transition Metals?

• Variable oxidation states Oxidative addition
Reductive elimination
• Variable coordination no. and geometry
• Capable of binding/activating substrates
• Steric factors and stereochemistry can be controlled
by ligands => selectivity (e.g. asymmetric catalysis
using chiral ligands)
29
General consideration of catalysis

(a) Uncatalyzed reaction,

higher activation barrier (DG*)

(b) Catalyzed reaction,

Lower activation barrier
Note. DGo is the same as that of (a)

(c) A pathway with an intermediate

that is more stable than the product

A catalyst increases the rate of a

reaction by introducing new pathway
with a smaller DG*; the reaction profile
contains no high peaks and no deep
troughs.
30
Catalytic performance:
• Turnover number, TON, (catalyst loading)
• Turnover frequency, TOF
• Selectivity (chemoselectivity, regioselectivity,
enantioselectivity)

Chirality 31
Catalytic cycle: a sequence of reaction that consumes the reactants and forms
the products, with the catalytic species being regenerated after the cycle.

Catalytic cycle

Precatalyst (18e/16e)
Product
forming step
catalyst (16e/14e)
P S
substrate &
reactant
C P S-C binding
substrate
S
modification C R
R
32
Catalysts
• Reactivity: rate of reaction (TOF)
• Stability: high turnover (TON)
• Selectivity: regio- and/or stereo-selectivity
of products

33
 Summary

Weak M-L bond=> faster MI

Migration or Insertion?
Decarbonylation of Mn(CO)4(*CO)(COMe) => migration pathway for MI

Homogeneous catalysis
➢ Advantages and disadvantages
➢ Why transition metals (variable oxidation state, activation mode and
selectivity control)
➢ Catalytic cycle (catalyst regeneration)
➢ Catalytic performance (reactivity, stability and selectivity)
34
(1) Rh-catalyzed hydrogenation of olefins

RhL3Cl H H Rh(PPh3)3Cl
+ H2
R L = PPh3 Wilkinson’s catalyst
R

•Ambient condition Use of a chiral catalyst

•Syn addition => asymmetric hydrogenation

•Terminal olefins are hydrogenated faster than internal ones

35
 Why mechanism is important?

➢ One mechanism can present a series of reactions (Suzuki,

Neigishi, Kumada, Sonogashira couplings).
➢ The mechanism can explain the reaction phenomenon.
➢ The mechanistic understanding can benefit the selectivity
control and efficiency enhancement.
➢ Researchers can develop new methodologies based on
mechanistic understanding.

36
 d8 square planar (16e rule)
Proposed Mechanism coordination compounds

RhL3Cl
H H
solv -L H2
R
RhL2Cl(solv)
Oxidative addition
Reductive solv = solvent
Elimination Cl
Cl L H
L H Rh
Rh L H
L solv
solv
(Alkyl comlex) R (hydride comlex)
H
Cl
L H
Rh R
L H
Migratory R
insertion (Olefin complex)

37
 Related catalytic reactions, hydro-X-tion

+ isomer

X = H, hydrogenation

X = SiR’3, hydrosilylation (will be discussed in main group chemistry)

X = BR’2, hydroboration

38
Co-catalyzed isomerization of alkenes:
Related catalysis involving migratory insertion and reductive elimination (1,2-shift)

Propanal Terminal olefin

Internal olefin

Migratory insertion
a
b-H elimination b

39
Rate decreases when excess PPh3 is added.
[RhL3Cl] H H
+ H2
R R

[RhL3Cl] H H
+ H2 (SLOWER)
R with excess L R
L = PPh3

The first step involves PPh3 dissociation

[Rh(PPh3)3Cl] “[Rh(PPh3)2Cl]” + PPh3

Precatalyst: RhL3Cl
Active form of catalyst : RhL2Cl or RhL2Cl(solv)
40
Quiz
[Rh(PEt3)3Cl] (A) or [Rh(PPh3)3Cl] (B), which is a
less active hydrogenation catalyst. Why?
more rich, better ligard
Sp I dissociation
Slower ligand
[Rh(PEt3)3Cl] “[Rh(PEt3)2Cl]” + PEt3 K1

[Rh(PPh3)3Cl] “[Rh(PPh3)2Cl]” + PPh3 K2

Sp
K2 > K1

41
[Tolman] Cone angle of phosphine ligands (q)
The angle of the cone that contains all the ligand

Large q
 PR3 is bulky C
 Large dissociation constant
M P
q C
Kd C
NiL4 NiL3 + L (at 25oC)
q Kd
PMe3 118o ~10-9
PEt3 132o ~10-5
PPh3 145o large

42
5:56:58 PM 43
Spacing-filling diagram Measurement of q
for Fe-PPh3 1 pm = 1x10-12 m

44
(2) Co-catalyzed hydroformylation of olefins
(oxo process)

R H [Co2(CO)8] R H
+ CO + H2 H CHO
H H 150oC, 250 atm H H

• Aldehydes, e.g. butyraldehyde (R = CH3), are versatile

chemical intermediates in industry
• The hydroformylation of long-chain alkenes is the basis for
production detergent alcohols

45
Proposed mechanism
O.A.

Pre-catalyst

R.E.
Catalyst

O.A.

M.I.

M.I.

46
Selectivity H2, CO CHO OHC H
H
+
R Co cat. R R
major minor
linear branched
R
1 2

Co H
H goes to C2 H goes to C1

R R H
H
R R
H H
CHO Co CHO
Primary alkyl complex Co
major Less crowded Secondary alkyl
More crowded minor
More stable
Less stable
47
•When P(n-Bu)3 is added, the linear/branch selectivity is
improved
R Bu R
Co Bu
P Bu
Bu Co P Bu
Bu
less stable
P steric repulsion

is a very bulky ligand

e.g. Addition of P(n-Bu)3 gives about 90% linear products (a mixture of

aldehyde and alcohols)

• However, PR3 increases the hydridic character of the hydride ligand

=> [HCo(CO)3(PR3)] is a strong hydrogenation catalyst
=> Side-products: alcohols (hydrogenation of aldehydes)
alkanes (hydrogenation of alkenes)

48
Rate dependence on CO partial pressure

•At low pressure, rate  as PCO

•Above a certain threshold, rate  as PCO 

At high pressure, CO suppresses the formation of one of the

catalytic species, [HCo(CO)3]. An increase in CO pressure will
lower the concentration of [HCo(CO)3]

HCo(CO)4 HCo(CO)3 + CO

49
Rh(I) catalyst
More selective than the Co catalyst

e.g. HRh(CO)(PPh3)3
The linear/branched ratio is as high as 20:1
(cf. 3:1 and 9:1 for HCo(CO)4 and HCo(CO)3(PBu3),
respectively)

50
Proposed mechanism for the Rh-catalyzed hydroformylation
cat. Rh(H)(CO)(PPh3)3
+ CO + H2 CHO
(i) R R

51
 Summary
Examples
•Dissociation of L
Cone angle of PR3
Isomerization of olefins
Hydro_x_ation
(e.g. hydrosilylation,hydroboration)

•Linear/branched
selectivity
•Effect of added PBu3

•Organometallic and organic

cycles, MeC(O)I intermediate

52
 (4) Monsanto acetic acid synthesis
• CH3OH + CO → CH3COOH
• 3.5 Mt of acetic acid are produced a year worldwide (e.g. used
in manufacture of vinyl acetate, cellulose acetates, and
pharmaceuticals)
• 60% of the world’s acetyls are manufactured using the
Monsanto process.
• Catalyst: [Rh(CO)2I2]- (or RhX3 + CO + I-)
• Mechanism: involves organometallic & organic cycles

• An alternative to the Rh catalyst is the Ir-catalyzed methanol

carbonylation commercialized by BP (Cativa Process)
catalyst: [Ir(CO)2I2]-

53
(i) Organometallic cycle
Me
I CO Rate-determining
Rh
OA I CO MI step
I
MeI
O

I C Me
-
I Rh
I
+ 1 CO I CO
Rh I
-
I CO

O
Me I
CO
C O I C Me
Rh
I OC CO
RE I

Overall reaction: MeI + CO → MeC(O)I

54
(ii) Organic cycle MeI
MeOH

HI H2O

Me
Me
C O
C O
I
HO

55
Cativa Process

56
 Why I-? (iodide is corrosive)

Iodide is
➢ A good leaving group
oxidative addition of Rh(I) with MeI is easy
➢ Soft, Rh(I) is soft
➢ A good nucleophile:
MeOH + HI → MeI + H2O is fast

57
➢ Problem:
Oxidation of [Rh(CO)2I2]- by HI
[Rh(CO)2I2]- + HI →[Rh(CO)2I4]- + H2 + CO

[Rh(CO)2I4]- loses CO easily => decomposition of catalyst

➢ Solution:
(i) Under a pressure of CO
(ii) Adding small amounts of H2

58
59
C-H Bond Activation

• No pre-functionalization is required
• Atom-economy
• Selectivity control

60
C-H Bond Activation by TM

61