SYNTHESIS, STRUCTURE AND CATALYTIC APPLICATION OF NOVEL CARBENE COMPLEXES WITH BENZOTHIAZOLIN 2 YLIDENE LIGANDS 1

Chapter One: Introduction Introduction
Chapter One
Introduction

Carbenes, the simplest being methylene CH
2
, are defined as neutral divalent
carbon species bearing two non-bonding electrons.
1
The existence of CH
2
was first
postulated in the 1930s.
1
However, definitive evidence for its existence did not come
until 1959.
1

Carbene chemistry has fascinated and challenged chemists for decades, and in
recent years this field has experienced tremendous growth. The first stable
nucleophilic N, N-heterocyclic carbene (NNHC) was isolated by Arduengo in 1991.
2

Conceptually, NHCs may be considered as phosphine mimics.
3
NHC ligands are
regarded as strong -donors with some degree of back-donation possible.
3
This type
of ligand can stabilize metals in various oxidation states in catalytic reactions.
4

NS NSNN NN
R
R R
RR R RR
NN
R R
R R
1.1 1.2
1.3 1.4
1.5
11
1
1
1
2
2
2
22

Fig 1.1 N-heterocyclic carbenes.
5


Most of the carbene work in literature is focused on N,N-heterocyclic carbenes
(NNHC). The NNHC (1.1-1.3) derived from imidazole, imidazoline and
benzimidazole have been successfully employed as ancillary ligands in catalysis.
5

One way to “enrich” a NNHC is to attach heteroatoms to the parent N,N-heterocycle

Synthesis, Structure and Catalytic Application of Novel Carbene Complexes with Benzothiazolin-2-ylidene
Ligands
1
Chapter One: Introduction Introduction

Synthesis, Structure and Catalytic Application of Novel Carbene Complexes with Benzothiazolin-2-ylidene
Ligands
2
carbene moiety. Such a strategy is being used to tune the electronic properties and the
donating abilities of NHC ligands.
6
Carbene complexes with thiazolin-2-ylidene (1.4)
and benzothiazolin-2-ylidene (1.5) ligands are more acidic compared to their
imidazolin-2-ylidene (1.1) and benzimidazolin-2-ylidene (1.3) analogues. The
replacement of N-R by S in the 1-position makes 1.4 and 1.5 better -acceptors due to
the availability of empty d-orbitals.
7
This larger sulfur atom bears no exocyclic
substituent and might be expected to diminish p-p interactions between the carbene
center and the neighboring heteroatoms (nitrogen) in this case.
8

Prior to this project, there were only a few reports of N,S-heterocyclic carbene
(NSHC) complexes and their use as catalysts.
8-14
As the electronic configuration of
NSHC and the chemical properties of its metal carbene bond, as well as the catalytic
activity are less known than NNHC,

3
it would be in our interest to explore this type of
compound. In this chapter, the development of NSHC ligands and their complexes
will be reviewed and its application in catalysis is discussed.

1.1 The Development of N,S-Heterocyclic Carbene
Complexes
Early work by Breslow described the application of N,S-heterocyclic carbene
or thiazolin-2-ylidene (1.6) as organocatalysts such as the vitamin B1 catalyzed
benzoin condensation reactions (Fig 1.2).
15-16

Transition metal complexes of NSHC were explored quite early. Lappert et al.
and Stone et al. are among the pioneers in synthesizing NNHC and NSHC (Table
1.1).
9-10
Rh(I)-NSHC complex (1.7) was reported in 1974 by Lappert.
9
Stone and his
co-workers managed to synthesize some cationic NSHC carbene complexes of Ir(III),
Chapter One: Introduction The Development of N,S-Heterocyclic Carbene Complexes

3
Synthesis, Structure and Catalytic App
lication of Novel Carbene Complexes with Benzothiazolin-2-ylidene
Ligands
Ni(II), Pd(II) and Pt(II) (1.8-1.15).
10(a)
Later, they also reported Ir(I), Rh(I), Mn(I),
Cr(0) and Fe(0)-NSHC complexes (1.16-1.23).

10(b)


S
N
Cl
HO
N
N
C
H
3
NH
2
1.6

Fig. 1.2 Thiamine (vitamin B1), a coenzyme.
15-16


Raubenheimer et al. reported the synthesis of complexes 1.24 and 1.25 in
1985, ca 10 years after the work of Stone and Lappert.
11(a)
They explored the Au(I)-
NSHC complexes (1.26-1.32) a few years later.
11(b)
Some of the thiazolyl and
thiazolinylidene complexes of cyclopentadienyliron(II) (1.33-1.40),
11(c)
and

molybdenum and tungsten, (1.41-1.44) were prepared and characterized by them.
11(d)

A Pd(II)-NSHC (1.45) was reported by Calò et al. at 2000. This complex was
studied in the Mizoroki-Heck reaction.
12
Hahn and Huynh et al. reported Ir(I)
complexes (1.46-1.49) with coordinated and pendant allyl substituent.
13
Grubbs et al.
also reported Ru(II)-NSHC (1.50-1.56) with applications in olefin metathesis.
14

The transition metal complexes of NSHC are less well known than the
complexes with NNHC ligands. Table 1.1 summarizes the transition metal complexes
with NSHC ligands that are currently known in the literature. As seen in Table 1.1,
only a limited numbers of complexes have been prepared. These complexes cover the
Group 6 and 8-11 transition metals. It clearly suggests that there is much room for the
future development of the chemistry of NSHC transition metal complexes.
Chapter One: Introduction The Development of N,S-Heterocyclic Carbene Complexes

4
Synthesis, Structure and Catalytic App
lication of Novel Carbene Complexes with Benzothiazolin-2-ylidene
Ligands
In the following section a comparison between some related NSHC and
NNHC complexes is discussed. In the literature, most of the syntheses of these
NSHC-complexes were done under inert condition and judicious handling was needed.
In section 1.4, the literature methods for preparation of NSHC- and selected NNHC
metal complexes are reviewed. These complexes are the currently known complexes

that are closely related or to a certain extent they are analogous. The synthesis of
NNHC forms the background of the synthetic route of NSHC complexes described in
this thesis.

Table 1.1 Complexes with thiazolin-2-ylidene ligands.
Complexes Ref.
N
S
Rh
Cl
CO
N
S
1.7


9

S
NR
Ir
Cl
CO
L
L
Cl
1.8: R = H, L = PMePh
2
1.9: R = Me, L = PMePh
2

S
NH
Ir
Cl
CO
L
L
Cl
1.10: L = PMePh
2

10(a)
Chapter One: Introduction The Development of N,S-Heterocyclic Carbene Complexes

5
Synthesis, Structure and Catalytic App
lication of Novel Carbene Complexes with Benzothiazolin-2-ylidene
Ligands

S
N
Cl(L)
2
M
1.11: M = Pt, L = PEt
3
1.12: M = Pt, L = PMePh
2
1.13: M = Pd, L = PPh

3
1.14: M = Pd, L = PMePh
2
1.15: M = Ni, L = PPh
3

S
N
M
PPh
3
OC
PPh
3
R
BX
4
1.16: M = Ir, R = Me, X=F

1.17: M = Rh, R = Me, X = F
1.18: M = Ir, R = Et, X = Ph

10(a)
10(b)

S
N
BF
4
1.19: M = Ir

1.20: M = Rh
M
PPh
3
PPh
3
OC

S
N
Mn
I
CO
CO
OC
OC
1.21

10(b)

S
N
Cr
C
O
CO
CO
OC
OC
1.22

S
N
Fe
1.23
CO
OC
CO
OC

10(b)

NS
C
r
(
C
O)
5
1.24: R = H
1.2
5
:
R
=Et
R

S
N
AuX

1.26: X = 2,4-dimethylthiazole
1.27: X = Cl
1.28: X = (C
6
F
5
)

S
N
H
AuPPh
3
PF
6
1.29

11(a)
11(b)
S
N
H
Au
PF
6
S
N
H
1.30

S
N
Au
S
N
H
1.31

S
N
Au
NBu
4
S
N
1.32

11(b)
Chapter One: Introduction The Development of N,S-Heterocyclic Carbene Complexes

6
Synthesis, Structure and Catalytic App
lication of Novel Carbene Complexes with Benzothiazolin-2-ylidene
Ligands
Fe
L
L
N
S
S

N
H
L-L
1.33: CNC6H4S-o dppe
1.34: CNC6H4S-o dppm
1.35: CNC(Me)CHS dppm
1.36: CNC(Me)CHS dppe
S
N

11(c)

S
N
Fe
OC
CO
CF
3
SO
1.37: CNC6H4S-o
1.38: CNC(Me)CHS
N
H
S

S
N
Fe
OC

CO
1.39: CNC6H4S-o
1.
4
0:
C
N
C
(
Me
)
C
HS
N
S

11(c)

N
S
M(CO)
5
1.41: M = Mo
1.42: M = W
1.43: M = Cr

N
S
W(CO)
5

1.44

11(d)
N
S
Pd
I
I
N
S
1.45

12(a)

Ir
Br
S
N
1.46

Ir
N
Br
S
H
1.47

13
Chapter One: Introduction The Development of N,S-Heterocyclic Carbene Complexes

Synthesis, Structure and Catalytic Application of Novel Carbene Complexes with Benzothiazolin-2-ylidene
Ligands
7

Ir
Br
S
N
1.48

Ir
Br
OC
OC
S
N
1.49

13
NSAr
Ru
Cl
Cl
O
Ar = , 1.50
, 1.51
, 1.52
, 1.53
, 1.54

14

NSAr
Ru
Ph
Cl
Cl
Ar =
PCy
3
, 1.55
, 1.56

14

1.2 The Comparison of NSHC- and NNHC- Metal
Complexes
Some of the NSHC- and NNHC- metal complexes are selected where they are
closely related. In this section, the similarity and differences of NSHC- and NNHC-
metal complexes are discussed. Caló et al. managed to isolate and characterize Pd(II)-
NSHC trans-1.45 in 2000.
12(a)
The analogous Pd(II) complex with 1,3-
di(benzyl)benzimidazolin-2-ylidene had been isolated by the Huynh group in 2005.
17

Both X-ray crystal structures of the Pd(II) complexes were characterized as the trans-
isomer (Table 1.2). Huynh et al reported that the yield of trans-1.46 could be
increased by using DMSO as solvent. Cis-1.45 readily converts to trans-1.45 within
1.5 h upon heating in DMA solvent at 100 C, as observed previously by Caló.

Chapter One: Introduction The Comparison of NSHC- and NNHC- Metal Complexes

8
Synthesis, Structure and Catalytic App
lication of Novel Carbene Complexes with Benzothiazolin-2-ylidene
Ligands
However, there is no report on such trans- to cis- isomerism for the related Pd(II)-
NNHC case with X = I.
The
13
C
carbene
NMR signals of trans-1.45 were more deshielded ( = 210.5
ppm) than trans-1.46 ( = 181.0 ppm). This is due to the better -acceptor behaviour
of NSHC resulting in a more acidic Pd metal center. However, the bond lengths and
angles of both complexes were not significantly different in solid state. Although both
complexes were studied in the Mizoroki-Heck reaction, their results could not be
directly compared as the conditions were different. However, both were active in
catalysis. The details of the catalytic application of Calo’s NSHC will be reviewed in
Section 1.5.

Table 1.2 A comparison of Pd(II)-NSHC and Pd(II)-NNHC metal complexes.
NSHC- NNHC-
Structure
N
S
Pd
I
I
N

S
transi
-
1.45

N
N
Pd
I
I
N
N
transi-1.46

Synthesis
N
S
H
I
Pd(OAc)
2
N
S
Pd
I
I
N
S
+
THF, Reflux

- 2 AcOH
trans-1.45
2
+
N
S
Pd
N
S
I
I
c
i
s-1.45

- yield of trans-: 80%
- cis- : 12%
N
N
H
I
Pd(OAc)
2
N
N
Pd
I
I
N
N

+
(i) or (ii)
- 2 AcOH
trans-1.46
2
+
N
N
Pd
N
N
I
I
cis-1.46

(i) THF, RT: trans-, 40%
cis-, 54%
(ii) DMSO, 80 C: trans-, 77%
cis-, 20%

 (
13
C
carbene
)
ppm
trans-,  = 210.5 ppm trans-,  = 181.0 ppm
Chapter One: Introduction The Comparison of NSHC- and NNHC- Metal Complexes

9

Synthesis, Structure and Catalytic App
lication of Novel Carbene Complexes with Benzothiazolin-2-ylidene
Ligands
Another relevant comparison is of Ir(I)-NSHC
13
and Ir(I)-NNHC
18
complexes.
Reaction of [Ir(

-OMe)(cod)]
2
with 3-(2-propenyl)benzothiazolium bromide or 1,3-
di(2-propenyl)benzimidazolium bromide under similar conditions gave different
complexes .

Ir
O
O
Ir
N
N
H
Br
+
2
Ir
N
N
Br

acetone
Ir
N
N
BF
4
AgBF
4
1.46 1.47

Scheme 1.1 Formation of Ir(I)-NNHC complexes 1.46-1.47.
20

For the Ir(I)-NNHC, the synthetic pathway was straightforward (Scheme 1.1)
where the five-coordinated and n
2
-C coordinated mode of Ir(I)-NNHC (1.46) was
obtained.
18
The cationic derivative [Ir(cod)(n
2
:n
2
-C-NNHC)]BF
4
, (1.47) was obtained
by treatment of 1.46 with AgBF
4
.
18

Instead of the target complex of the five-
coordinated Ir(I) for NSHC complex (1.48) (Scheme 1.2),
13
similar reaction gives the
unexpected complex, N-coordinated unsubstituted benzothiazole ligand complex, 1.49.
The difference can be explained by the radical [1,3]-sigmatropic rearrangement of N-
allyl dibenzotetraazafalvalene. In order to obtain complex 1.48, a different synthetic
pathway was designed. [Ir(

-Cl)(cod)]
2
is used as the substrate to react with AgBF
4

in CH
3
CN to help replace chloride by CH
3
CN. The benzothiazolium salt was added
followed by KO
t
Bu as an external base. Using this procedure, the five-coordinated
Ir(I)-NSHC (1.48) was obtained.
The reaction between [Ir(

-Cl)(cod)]
2
and 1,3-di(2-propenyl)-
benzimidazolium bromide in ethanol with excess of NaOEt gives the four-coordinate
complex 1.52 (Scheme 1.3).

13
The excess presence of NaOEt leads to slow
Chapter One: Introduction The Comparison of NSHC- and NNHC- Metal Complexes

10
Synthesis, Structure and Catalytic App
lication of Novel Carbene Complexes with Benzothiazolin-2-ylidene
Ligands
hydrogenation of the carbene ligand allyl substituents. Ir(I)-NSHC 1.50 with the N-
propylbenzothiazolin-2-ylidene ligand was obtained by using the excess of NaH.
Bubbling CO into the solution of 1.50 affords complex 1.51.
13


Ir
O
O
Ir
N
S
H
Br
+
2
Ir
Cl
Cl
Ir
2 AgBF
4

CH
3
CN
Ir
NCCH
3
NCCH
3
BF
4
N
S
H
Br
Ir
Br
N
S
BF
4
Ir
Br
S
N
1.48
Ir
N
Br
S
H

1.49
Ir
Br
S
N
1.50
Ir
Br
OC
OC
S
N
1.51
CO
CH
2
Cl
2
KO
t
Bu
NaH
acetone

Scheme 1.2 Formation of Ir(I)-NSHC complexes 1.48-1.51.
13

Ir
Cl
Cl

Ir
N
N
H
Br
Ir
N
N
Ir
Br
N
N
1.52
Br
+
NaOEt
EtOH

Scheme 1.3 Formation of Ir(I)-NNHC complex 1.52.
13

The two examples given above suggest that there are times when different
formation pathways could be needed for the analogous NSHC and NNHC complexes.
Their catalytic properties have not been studied yet.
Table 1.3 shows the comparison of
13
C
carbene
NMR signals and selected Ir-C
bonds for analogous NSHC and NNHC complexes. All the chemical shifts for the

Chapter One: Introduction The Comparison of NSHC- and NNHC- Metal Complexes

Synthesis, Structure and Catalytic Application of Novel Carbene Complexes with Benzothiazolin-2-ylidene
Ligands
11
carbon resonances of Ir(I)-NSHC complexes are shifted downfield ( = 202.1 - 218.9
ppm) compared to the analogous complex with NNHC ( = 172.3 – 191.2 ppm). The
Ir-C
carbene
distances in complexes with NSHC ligands are comparable with the
analogous benzimidazolin-2-ylidene complexes, which indicates that both the N,N-
and N,S-stabilized carbene ligands have -donor properties.
13, 18


Table 1.3 Comparison of the
13
C
carbene
NMR signals and selected Ir-C
carbene
bond data of
analogous NSHC and NNHC complexes.

Complexes L = NSHC L = NNHC

 (
13
C
carbene

)(ppm)
a
 (
13
C
carbene
)(ppm)
b

IrBr(cod)(n
2
-C-L) 202.1 (1.46) 172.3 (1.49)
[Ir(cod)(n
2
, n
2
-C-L)]BF
4
- 173.3 (1.50)
IrBr(cod)(C-L) 218.9 (1.52) 191.2 (1.51)
IrBr(CO)
2
(L) 209.2 (1.48) -


Ir-C
carbene
Length (Å) Ir-C
carbene
Length (Å)

IrBr(cod)(n
2
-C-L) 1.98(6) (1.46) 2.02(3) (1.49)
[Ir(cod)(n
2
, n
2
-C-L)]BF
4
- 1.94(2) (1.50)
IrBr(cod)(C-L) 1.98(4) (1.52) 2.01(4) (1.51)
a: Measured in CD
2
Cl
2
.
b: Measssured in CDCl
3
.


1.3 Preparative Methods for NSHC- and NNHC- Metal
Complexes
In this section, the literature of synthetic methods of metal-carbene complexes
will be reviewed. Some of the NNHC metal complexes are discussed in comparison
with NSHC metal complexes.

Chapter One: Introduction Preparative methods for NSHC- and NNHC- Metal Complexes

12

Synthesis, Structure and Catalytic App
lication of Novel Carbene Complexes with Benzothiazolin-2-ylidene
Ligands
1.3.1 Preparation of N,S- and N,N-heterocyclic Carbenes
A variety of methods for the generation of free carbenes are known (Scheme
1.4). The most commonly used method is based on deprotonation at the C2-position
of the azolium salts with bases such as, Li(NiPr
2
) (LDA) and K[N(SiMe
3
)
2
] (Scheme
1.4 (a)) to yield the corresponding free carbenes.
19

The stable carbene 3-(2, 6-diisopropylphenyl) thiazole-2-ylidene is formed
from the reaction of 3-(2, 6-diisopropylphenyl)-4,5-dimethylthiazolium chloride with
potassium hydride in tetrahydrofuran (THF) at room temperature (Scheme 1.4 (b)). In
the presence of a protic acid, the dimerization reaction would proceeds smoothly.
Both monomer and dimer of 3-(2,6-diisopropylphenyl) thiazole-2-ylidenes have been
isolated.
8


N
N
R
H
base

THF, r.t.
R'
X
N
N
R
R'
R''
R''
R''
R''
(a)
N
N
R'
R'
R
R
S
N
N
R'
R'
R
R
K
THF,
(c)
S
N

i
Pr
(b)
H
N
N
N
Ph
Ph
Ph
N
N
N
Ph
Ph
P
h
vacuum
- MeOH
(d)
OMe
H
S
N
i
Pr
S
N
S
N

[H]
+
KH
THF, r.t.
C
2 position
i
Pr
Pr
i


Scheme 1.4 Different approaches to preparation of free NSHCs and NNHCs.
8, 20-31

Chapter One: Introduction Preparative methods for NSHC- and NNHC- Metal Complexes

13
Synthesis, Structure and Catalytic App
lication of Novel Carbene Complexes with Benzothiazolin-2-ylidene
Ligands
A different route to generate free NHCs involves the reductive desulfurisation
of imidazolin-2-thiones with potassium in refluxing THF (Scheme 1.4 (c)). This
reaction gives the corresponding imidazolin-2-ylidenes in high yield.
22

Thermal elimination of methanol from a 5-methoxytriazole allowed the
isolation of the first triazole based free NHC (Scheme 1.4 (d)). This carbene was the
first commercially available free carbene.
23

This method is also used for preparation
the NHC’s from imidazolidines
23-26
and benzimidazolines.
27

(a)
N
N
N
N
R R
R R
N
N
2
R
R
N
S
H
X
N
S
N
S
N
S
N
S

(b)
N
S
H
X
N
S
N
S
N
S
N
S
(c)
Et
3
N
0
o
C
90
o
C
2 h
O
O
Et
3
N
0

o
C
O
2
N
N
R
H
R
X
base

Scheme 1.5 Chemical reactivities of selected azolium salts.
8, 21-31


Equilibrium mixtures of tetraaminoethylene and free NHC have been studied
for some benzimidazolin-2-ylidenes (R=iso-butyl) (Scheme 1.5 a).
28
This equilibrium
known as the Wanzlick Equilibrium is postulated more than 30 years ago.
29-30
However, this is not observed for benzothiazolin-2-ylidene.
A [1,3]-sigmatropic rearrangement of the electron-rich olefin occurs when the
ethylene dimer is heated to 90 C for 2 hours (Scheme 1.5 b).
31
These ethylene dimers
Chapter One: Introduction Preparative methods for NSHC- and NNHC- Metal Complexes

14

Synthesis, Structure and Catalytic App
lication of Novel Carbene Complexes with Benzothiazolin-2-ylidene
Ligands
are highly sensitive to oxygen. Baldwin et. al reported that exposure of a
dichloromethane solution of 3-methylbenzothiazole-2-ylidene dimer to oxygen at 0
C gave the amide compound in high yield (Scheme 1.5 c).
32


1.3.2 Preparative methods based on NNHC’s
The NNHC carbene complexes were previously prepared by the coordination
of the free NNHC ligand to a metal precursor. Free NNHCs are strong -donor
ligands that can displace other donor ligands such as phosphines from both Pd(0)
33-36

and Pd(II)
37-40
phosphine complexes.

[(COD)Pd(NQ)]
THF, -78
o
C to RT
NQ = 1, 4-naphthoquinone
1.57
N
N
N
N
Pd

N
N
Pd
O
O
O
O


Scheme 1.6 Synthesis of dinuclear Pd(II) complex from the coordination of the free NNHC
ligand to [(COD)Pd(NQ)] 1.57.
42


Scheme 1.6 shows the reaction of the free NNHC IMes and [(COD)Pd(NQ)]
to yield a Pd(0) complex 1.57. The NNHC can also displace the 1,5-cyclooctadiene
ligand in the Pd(II) precursors [MCl
2
(COD)] to form Pd(II) dinuclear complexes
[Pd
II
L(NNHC)(

-X)]
2.
41-43
Other mixed-ligand complexes such as
Pd
II
X

2
(NNHC)(PR
3
),
44
Pd
0
(NNHC)(PR
3
),
33,45
Pd
0
(NNHC)(NNHC’),
45
and
Pd
II
(hydrocarby)(NNHC)
38,46-47
complexes can be obtained by this synthetic route.
Chapter One: Introduction Preparative methods for NSHC- and NNHC- Metal Complexes

15
Synthesis, Structure and Catalytic App
lication of Novel Carbene Complexes with Benzothiazolin-2-ylidene
Ligands
Other metal carbene complexes synthesized by the coordination of the free
NNHC ligands include Cr,
48

Mn,
49
, Co,
51
Re,
50
Ru,
51-53
Rh,
54
Pt,
55
Cu,
56
Ge,
57
Ga
58

complexes. Extra precaution is needed to handle the air- and moisture-sensitive free
NNHC ligands when this method is employed. This method is still rare in
synthesizing NSHC-metal complexes. This is probably because the [1,3]-sigmatropic
rearrangement can occur.

1.3.3. Preparative methods based on bond cleavage of electron rich
olefins
Another approach to generate heterocyclic carbene complexes involves the
bond cleavage of the “carbene dimer” (an electron-rich olefin (ERO)) in the presence
of appropriate metal precursors. This method was employed extensively and has been
reviewed by Lappert and co-workers.

59-62


S
N
N
S
S
N
N
S
Rh
CO
Cl
[RhCl(CO)
2
]
2
1.7

Scheme 1.7 Synthesis of Rh(I) by bond cleavage of an electron rich olefins.
59


Scheme 1.7 shows the synthesis of a Rh(I) complex 1.7 using the ERO
approach. Mono-, di- or tri-carbene complexes of Cr, Mo, W, Mn, Fe, Ru, Ir, Os, Co,
Ni and Au in various oxidation states were obtained by using this preparative
method.
45-46,63
Other complexes with benzimidazolin-2-ylidene ligands have been

synthesized by cleaving of ERO by PdI
2
,
64-65
[{RhCl(cod)}
2
]
66
or [Mo(nor)(CO)
4
]
28
(nor = norbornadiene). A limitation of this ERO-based synthesis approach is that the
Chapter One: Introduction Preparative methods for NSHC- and NNHC- Metal Complexes

16
Synthesis, Structure and Catalytic App
lication of Novel Carbene Complexes with Benzothiazolin-2-ylidene
Ligands
EROs are only accessible with NNHCs containing primary alkyl or unhindered aryl as
substituents.
56

1.3.4. Preparative methods based on imidazolium salts with basic
metal
Preparation of carbene complexes from azolium salts and palladium acetate is
the most commonly used synthetic method. This method involves the deprotonation
of an appropriate azolium salt by a basic metal. Pd(OAc)
2
is a preferred precursor in

the preparation of Pd(II) carbene complexes.
33
However, metal precursors with
acetylacetonates and alkoxides have also been used.
67
The use of imidazolium halides
or imidazolium salts of other coordinating counterions gives products PdX
2
(NNHC)
2

(X = anion of imidazolium salt). The first report of this method involved the reaction
of Hg(OAc)
2
and 1,3-diphenylimidazolium perchlorate.
68
The advantages of the
deprotonation method are simplicity, relative stability toward oxygen and moisture,
with the reaction normally involving only one step without the need to isolate free
carbene.

N
S
H
I
Pd(OAc)
2
N
S
Pd

I
I
N
S
THF
+
Reflux
1.45

Scheme 1.8 Synthesis of a Pd(II) carbene complex 1.45 from Pd(OAc)
2
.
12


The Pd(II) carbene complex with 3-methylbenzothiazolin-2-ylidene 1.45 was
synthesized by using the method as shown in Scheme 1.8.
12
However, this method has
successfully applied mainly to Pd(II) carbene complexes.
Chapter One: Introduction Preparative methods for NSHC- and NNHC- Metal Complexes

Synthesis, Structure and Catalytic Application of Novel Carbene Complexes with Benzothiazolin-2-ylidene
Ligands
17
Other metal precursors such as [(cod)Ir(

-OR)
2
Ir(cod)] can be used for the

synthesis of carbene complexes.
69
This method based on azolium salts with basic
metal has been used to synthesize a variety of carbene complexes of Group 6 to 11
metals from benzimidazolium, benzothiazolium, pyrazolium, triazolium and
tetrazolium salts.
70
Moreover, this method can be modified by using bases such as
NaH, NaOAc, KOtBu or MHMDS (M = Li, Na, K). Many NHC complexes bearing
three-,
71-72
four-,
51
six-
73
or seven
74
-membered cycles have been synthesized by in situ
deprotonation of azolium salts.

1.3.5 Preparative methods based on transmetallation from lithiated
heterocycles
N-heterocyclic carbene complexes can be obtained from lithiated heterocycles
(azoles) by transmetallation. Raubenheimer and co-workers have reported the
preparation of carbene complexes from lithiated heterocycles. The reaction involved
the initial deprotonation of an azole compounds followed by an alkylation reaction.
11(e)

(CO)
5

Cr C
OEt
Ph
+
N
S
Li
H
N
S
N
S
(OC)
5
Cr
(OC)
5
Cr
Et
HCl / Et
2
O
[Et
3
O][BF
4
]
1.24
1.25

Scheme 1.9 Reaction of 2-lithiobenzothiazole with [Cr(CO)
5
{C(OEt)Ph}].
11(a)

Scheme 1.9 shows the reaction of 2-lithiobenzothiazole (LiBtz) with
[Cr(CO)
5
{C(OEt)Ph}].
11(a)
In this reaction, the alkoxyphenylcarbene ligand is
Chapter One: Introduction Preparative methods for NSHC- and NNHC- Metal Complexes

18
Synthesis, Structure and Catalytic App
lication of Novel Carbene Complexes with Benzothiazolin-2-ylidene
Ligands
replaced and complexes 1.24 and 1.25 are formed upon acidification or alkylation.
Both of these complexes were isolated in extremely low yields (1% and 5%
respectively). Another limitation of this method is the use of highly sensitive lithio-
compounds.
Several N,S-heterocyclic carbene complexes containing Cr, Mo, W,
11(a), 11(d)

Fe
11(c),75
and Au
11(b),76
have been prepared from a lithiated thiazole. Hahn and
Waldvogel et al. obtained W-NNHC complexes from the reaction of lithiated N-

ethylbenzimidazole and [W(CO)
5
(thf)]. Subsequently, this compound reacts with HCl
yielding the tungsten complex with a NH,NR-stabilized benzimidazolin-2-ylidene
ligand.
77


1.3.6. Preparative methods based on carbene transfer to other metal-
NNHC/NSHC complexes
Besides the above synthetic routes, carbene transfer is another useful way of
obtaining transition metal carbene complexes. Complexes of Ni(II),
78-79
Pd(II),
80

Pt(II),
81
Au(I),
82-91
Rh(I),
92-101
Ir(I),
96,100,102
Ru(II),
103-108
Ru(III),
106
Cu(I),
85,108-113

Cu(II),
108,109,111,113
have been prepared. This method is particularly useful for
preparing carbene complexes with NNHC ligands bearing base-sensitive functional
groups or an activated -hydrogen. Pd(II)-NNHC complexes were obtained by
transferring of the NNHC ligand from a Ag(I)-NNHC complex to various Pd(II) metal
precursors: PdCl
2
,
114-116
PdCl
2
(CH
3
CN)
2
,
83-84,117-124
PdCl
2
(PhCN)
2
,
95,119

[Pd(allyl)Cl]
2
,
125-126

Pd(cod)CH
3
Cl,
41,118-119,127-128
Pd(cod)Cl
2
,
41,118,119,128-130
Pd(cod)Br
2
,
41
Pd(cod)CH
3
Br.
41
Ag(I)-NNHC complexes can be prepared from Ag
2
O
and carbene precursors and they have become widely used carbene transfer
Chapter One: Introduction Preparative methods for NSHC- and NNHC- Metal Complexes

19
Synthesis, Structure and Catalytic App
lication of Novel Carbene Complexes with Benzothiazolin-2-ylidene
Ligands
reagents.
131
Carbene transfer reactions can be carried out under aerobic conditions and
in the presence of water.

83
It offers great advantages to those reactions which were
previously carried out under an inert atmosphere.
83


N
N
Et
Et
H
Br
N
N
Et
Et
N
N
Et
Et
Ag
AgBr
2
Ag
2
O
Pd(MeCN)
2
Cl
2

-AgBr
N
N
Et
Et
N
N
Et
Et
Pd
Cl
Cl
1.58
1.59

Scheme 1.10 Transfer of carbene ligand from Ag(I)-NNHC complex 1.58 to Pd(MeCN)
2
Cl
2

to give Pd(II) carbene complex 1.59.
84,124-133

This method has become popular since it was discovered by Wan and Lin in
1998.
84,132-133
They have shown that Ag(I)-NHC complex 1.58 can be used as a
convenient reagent to transfer the NNHC ligand to a Pd(II) precursor, giving Pd(II)-
NNHC complex 1.59 (Scheme 1.10).
The study of the Ag(I) carbene intermediates have been discussed in the

literature
80(b),134
and notably AgX(NNHC) and [Ag(NNHC)
2
][AgX
2
], in their
dinuclear forms.
135
Other more in-depth reviews on Ag(I)-NNHC carbenes are also
available.
130-131
Garrison and Youngs have reviewed the properties of silver NNHC
complexes.
136
The coordination chemistry of Ag(I)-NNHC complexes and their
antibiotic properties have also been described.
137


N
N
R
R
M(CO)
5
N
N
Pd
N

N
Cl
Cl
R
R R
R
PdCl
2
(PhCN)
2
DCM, r.t.
M = Cr (1.60), Mo (1.61), W (1.62)
1.63
+M(CO)
3
(PhCN)
2
+2(CO)
2

Scheme 1.11 Tramsmetallation of imidazolin-2-ylidene ligands in Cr, Mo and W complexes
to a Pd(II) complex.
80(a),121

Chapter One: Introduction Preparative methods for NSHC- and NNHC- Metal Complexes

Synthesis, Structure and Catalytic Application of Novel Carbene Complexes with Benzothiazolin-2-ylidene
Ligands
20
Cr, Mo and W complexes (1.60-1.63) with saturated imidazolin-2-ylidene

ligands have been used as reagents to transfer the corresponding carbene ligands to
Pd(II) (Scheme 1.11).
80(a),121
There are some rare cases where the pyrazolin-3-ylidene
ligands of chromium complexes were transferred to Au(I), Pd(II) and Pt(II)
complexes.
138


NSAr
Cl
NSAr
Ru
Ph
Cl
Cl
PCy
3
Ru
Ph
Cl
Cl
1) Ag
2
O, CH
2
Cl
2
, r. t.
2)

Ar =
PCy
3
PCy
3
, 1.55
, 1.56

Scheme 1.12 Ruthenium carbene complexes with thiazole-2-ylidene ligands prepared by the
carbene transfer method.
14


Grubbs and co-workers used the carbene transfer method to synthesize
ruthenium carbene complexes. A new series of ruthenium-based olefin metathesis
catalysts bearing thiazole-2-ylidene ligands, 1.55 and 1.56 were prepared in this way
(Scheme 1.12).
14


1.3.7. Preparative methods based on the oxidative addition of M
0
by
imidazolium salts
The oxidative addition of 2-chloro derivatives of azolium salts (5-
methylthiazole, benzothiazole, benzoxazole and N-methyl-2-chloro-5-
methylthiazolium cation) to complexes of iridium, palladium, platinum and nickel
were first described by Stone et al.
10
and Roper et al.

139
For example, oxidative
addition of 2-chlorobenzothiazole to IrCl(CO)(PMe
2
Ph)
2
afforded
IrCl
2
(CO)(NSHC)(PMe
2
Ph) 1.64 (Scheme 1.13).
10(a)

Chapter One: Introduction Preparative methods for NSHC- and NNHC- Metal Complexes

21
Synthesis, Structure and Catalytic App
lication of Novel Carbene Complexes with Benzothiazolin-2-ylidene
Ligands
Various NNHC complexes were pepared by oxidative addition of azolium
salts to low-valent metal precursors (Ni
0
, Pd
0
, Pt
0
, Rh
I
, Ir

I
, Fe
0
, Mn
0
, Cr
I
).
10(b),140
.
This requires C
2
-X bond activation (C
2
= carbon at 2-position between S and N; X =
halogen)

S
N
Cl
S
NH
Ir
C
l
PMe
2
Ph
CO
Cl

PhMe
2
P
IrCl(CO)(PMe
2
Ph)
2
1.64

Scheme 1.13 Preparation of IrCl
2
(CO)(NSHC)(PMe
2
Ph) complex by oxidative addition of a
2-chlorobenzothiazole to a IrCl(CO)(PMe
2
Ph)
2
precursor.
10(a)


N
N
M
N
N
Mes
Mes Mes
Mes

+
N
N
BF
4
r. t.
THF
N
N
M
N
N
H
N
N
Mes
MesMes
Mes
BF
4
M = Ni, 1.65
Pd, 1.66
M = Ni, 1.67
Pd, 1.68

Scheme 1.14 The oxidative addition reaction of imidazolium salts with low-valent (M = Pd,
Ni) to give carbene-M-hyrido complexes.
141-142

Cavell and co-workers showed that the oxidative addition of imidazolium salts
to Ni(0)-NNHC 1.65 at ambient temperature or Pd(0)-NNHC 1.66 at 55 C led to
tris(NNHC) hydrido complexes 1.67-1.68 (Scheme 1.14).
141-142
They also reported the
density functional calculations suggesting that the M
II
(hydrido)(NNHC) complexes
could be generated by oxidative addition of 2-H-imidazolium salts to zerovalent
Group 10 metal precursors.
140(b),143
The aforementioned oxidative addition reactions
may be relevant to the application of imidazolium salts (typically ionic liquids) in
catalysis with low-valent M
0
(M = Pd, Ni) complexes bearing strong -donor ligands
Chapter One: Introduction Preparative methods for NSHC- and NNHC- Metal Complexes

22
Synthesis, Structure and Catalytic App
lication of Novel Carbene Complexes with Benzothiazolin-2-ylidene
Ligands
as precatalysts.
144
Some NNHC-metal complexes were synthesized by oxidative
addition, for example the Pt(II),
145-147
Pd(II),
148-150
Ir(III)

151
Ru(III),
151
Os(III)
152
and
Ga(III)
153
NNHC-complexes.


Pd
H
3
C
N
N
BF
4

H
N
N
BF
4
+COD+Pd(
1.69 1.70
0)

Scheme 1.15 Reductive elimination of a Pd(II)-NHC complex.

3(e), 47, 155-156


The ‘reverse’ reaction, namely the reductive elimination of 2-
organylimidazolium salts from Pd
II
(hydrocarbyl)(NNHC) complexes, was also found
to be facile under certain circumstances.
154
Cavell et al. synthesized a variety of
methylpalladium carbene complexes of the type [Pd(Me)(NNHC)(chelate)] (chelate =
cod) from 1,3-dimethylimidazolium-2-ylidene and PdClMe(cod) where a methyl
ligand is cis to the NNHC ligand.
37,47,127
The cationic complex
{[Pd(Me)(dmiy)(cod)][BF
4
] (dimy = dimethylimidazolin-2-ylidene) 1.69 has three
different type of Pd-carbon bonds and it decomposes upon heating to Pd
0
, cod and the
1,2,3-trimethylimidazolium salt 1.70 (Scheme 1.15).
3(e),

47,155
The reductive
elimination process could be considered as an important pathway in the deactivation
of catalytically active NNHC complexes as suggested by theoretical and experimental
studies.
117, 156-157

Cavell et al. combined the principle of oxidative addition and reductive
elimination reactions (Scheme 1.16).
158-159
The nickel catalyst [Ni(PPh
3
)
2
] which was
generated in situ underwent oxidative addition to the C
2
-H bond of an imidazolium
salt to form a nickel(II) hydrido complex. The alkene is then inserted into the Ni-H
Chapter One: Introduction Preparative methods for NSHC- and NNHC- Metal Complexes

Synthesis, Structure and Catalytic Application of Novel Carbene Complexes with Benzothiazolin-2-ylidene
Ligands
23
bond in this complex. This was followed by reductive elimination to give the 2-
alkylimidazolium salt 1.73.

N
N
H
X
+
R
N
N
X
R

cat.
[Ni(cod)
2
/PPh
3
]
(1: 2.1)
RT or 55
o
C
48 h
(5 equiv)
1.71(a), X = BF
4
1.72(b), X = Br
R = Bu, Ph, H
35 - 100 %
1.73(a-b)

Scheme 1.16 Imidazolium C-H/Alkene Coupling Reaction.
158-159


1.3.8 Preparative methods based on template synthesis of metal
carbene complexes
Template synthesis is another method used to prepare metal carbene
complexes. Pd(II)-NHC and Pt(II)-NHC complexes can be obtained by reacting the
aziridine, thirane, oxirane or epoxides with isocyanide ligands or isocyanic acid
bound to Pd(II) or Pt(II).
160-168

Scheme 1.17 shows the reaction of isocyanide ligands
in Pd(II) with thiirane affording the corresponding NSHC derivatives, 1.74.
160
Ruiz et
al. synthesized Mn(I) NHC complexes by metal-mediated coupling of
propargylamines or propargylic alcohols and isocyanide ligands.
169
Hahn et al. also
reported the Pt(II) tetracarbene complexes from the template synthesis of
[Pt(PMe
3
)
4
](CF
3
SO
3
)
2

with 2-azidophenyl ligands.
170

There has been recent interest in NH,O- and NR,O-benzoxazolin-2-ylidene
ligands
171-175
and Cr,
176
W,
176-177

Re,
178
Fe,
179
Pd,
180
Pt
180
and B
181
complexes. Scheme
1.18 shows the synthesis of Pd(II) carbene complex 1.76 by template synthesis. Pd(II).
Chapter One: Introduction Preparative methods for NSHC- and NNHC- Metal Complexes

Synthesis, Structure and Catalytic App
lication of Novel Carbene Complexes with Benzothiazolin-2-ylidene
Ligands
24
Pt(II) complexes with benzo[1,3]oxazin-2-ylidene heterocycles were prepared by
using the cyclization of a -functionalized phenyl isocyanide.
182

Pd
Cl
L
CCl N R
+
S
Pd
Cl

L
Cl
S
N
R
THF, 25
o
C
L = PPh
3
, PMe
2
Ph
R = C
6
H
4
OMe-4, C
6
H
11
NC, C
6
H
11
1.74

Scheme 1.17 Preparation of Pd(II) carbene complexes 1.74 from the reaction of coordinated
isocyanide ligand with thiirane.
160

PdI
2
+
N
OSiMe
3
C
2
CH
3
CN
PdI
I
Bu
4
NF/MeOH
PdI
I
C
C
N
N
Me
3
SiO
OSiMe
3
OHN

ONH
- 2 SiMe
3
1.7
5
1.76

Scheme 1.18 Preparation of Pd(II) carbene complexes by template synthesis.
180


Re
Cl
Ph
3
P
Ph
3
PCl
C
Cl
N
OH
R
e
(
III
)
, 1.77

Re
Cl
Cl
Cl
O
N
O
O
N
H H
O
PPh
3
Re
(
V
)
, 1.78

Fig. 1.3 Re(III) complex 1.77 and Re(V) carbene complex 1.78.
178(a)

The intramolecular nucleophilic attack is influenced by the MCNR -
backbonding or d* back-bonding from the metal center to the isocyanide. For
Chapter One: Introduction Preparative methods for NSHC- and NNHC- Metal Complexes

Synthesis, Structure and Catalytic Application of Novel Carbene Complexes with Benzothiazolin-2-ylidene
Ligands
25
example, the complex with a Re(III) center 1.77, which is a more electron-rich metal

center, is more stable upon cyclization compared to Re(V) 1.78 (Fig. 1.3).
178(a)


1.4 Application of Metal NSHC Complexes in Catalysis
Many metal complexes with NNHC ligands are known to be active in
homogeneous catalysis. Such complexes are supported by the strong -donor
properties of the ligand.
183
As NSHC ligands have also similar -donor properties,
they should also be able to support many catalytically active complexes.
The mechanism of Pd-NNHC-mediated cross-coupling reactions is similar to
those catalyzed by the Pd-phosphine complexes.
3(f)
The established mechanism is
believed to involve three steps: oxidative addition, transmetallation and reductive
elimination in Mizoroki-Heck and Suzuki-Miyaura reactions.
3(f)
The choice of
solvent, temperature and transmetallation promoters (e.g. bases and additives) could
influence the catalytic efficiency.
3(f)
The Mizoroki-Heck
184-195
and the Suzuki-
Miyaura
3(h),

196-208
reactions catalyzed by Pd-NNHC complexes

4, 186(a),209-211
have been
extensively reported.
Although NSHC-metal complexes have been known since the 1970’s,
7,8
the
catalytic activity of Pd(II)-NSHC complexes was not explored until early 2000’s. A
catalytically active Pd(II) complex with 3-methylbenzothiazolin-2-ylidene 1.45 (Fig.
1.4) was synthesized and characterized by Caló et. al
12

Complex 1.45 is a useful precatalyst, showing good catalytic activity in the
coupling of aryl iodides and bromides with styrene or butyl acrylate with TONs of up
to one million using 10
-4
mol% of 1.45 in DMA or DMF (Scheme 1.19).
12(a), 12(g)-(h)