Synthetic and structural studies of copper, gold and palladium heterocyclic carbene complexes

1
Chapter 1. Introduction


1. General Properties of N-Heterocyclic Carbenes (NHCs)
N-heterocyclic carbenes (NHCs) have attracted significant interest over the
past decade as versatile and prolific ligands in catalysis, triggered mainly by
the starting use of NHC complexes in catalysis by Herrmann and co-workers,
1
and the preparation of Grubbs‘ second-generation and related catalysts.
2-5

Back in 1993, transition metal heterocarbenes were believed to exhibit
bonding properties similar to those of trialkylphosphines and
alkylphosphinates.
6
Six years later, Nolan et al. reported that, based on
structural and thermochemical studies, NHCs, with the exception of the
sterically demanding (adamantyl) carbene, generally behave as better donors
than the best phosphines donor ligands.
7
In numerous instances, simple
substitution reaction routes involving replacement of phosphines by NHC
ligands improved not only the catalytic activity but also thermal stability of the
resulting organometallic complexes. This is presumably due to the more
powerful σ-donating ability of NHCs than the closely related phosphine
ligands, forming stronger bonds to transition metals and thereby also leading
to electron-rich metal centers.
8-11
As phosphine mimics, NHCs avoid the

drawbacks of phosphine ligands such as air sensitivity, high toxicity and
thermal instability. In addition, it is relatively easy to modify the structural and
electronic components of the NHC manifold to bring a range of desirable traits
to the NHC-stabilized compounds.

As a result of the rapid and extensive development in NHCs work, many

2
review articles on NHCs have been published,
12-18
and NHCs continue to be a
hot research topic in organometallics, as evident from over 100 NHC-related
publications appearing in JACS alone in the two-year period of 2008-2009.
19

However, most of these studies were focused on Pd-, Ni-, Ru- and Rh-NHC
complexes. NHC complexes of copper and gold have been relatively
overlooked in spite of the wide use of copper and gold in catalysis, medicine
etc.
20-31


Preparations of copper and gold NHC complexes have been reported for
decades.
15
For example, Arduengo and co-worker isolated the first copper
carbene complex in 1993.
32
Study of gold NHC complexes started even earlier.
In 1974, Lappert‘s group reported the generation of ionic complexes

[Au(NHC)
2
]X (X = anion) from electron-rich olefins.
33
In the same year,
Fehlhammer‘s group also claimed the formation of Au(I)- and Au(III)-NHC
complexes through the spontaneous cyclization of isocyanide ligands.
34
In
1989, Au(I)-NHC complexes were isolated by Burini et al. through the
reaction of AuCl(PPh
3
) with lithiated benzylimidazoles, followed by
protonation.
35
However, copper and gold NHC complexes did not attract
significant research interest in the past.

With fruitful advancement in the study of transition-metal NHC complexes,
the value of copper and gold NHC complexes is being increasingly
appreciated by current researchers.
17,36-47
The research interest centers on the
structural and bonding curiosities of σ-dominant carbene moiety on the
electron-rich and soft late-metals that usually require an intricate balance of σ

3
and π ligands.
48,49
Another key focus is on the application of copper and gold

NHC complexes in catalysis and medicine.
50
Recent developments in the
chemistry of copper and gold NHC complexes are summarized herein.
17,36-43


1.1 Copper(I) N-Heterocyclic Carbene Complexes
1.1.1 General Synthetic Methods for Cu(I)-NHC Complexes
Four methods are usually applied in the synthesis of Cu(I)-NHC complexes
15

(Scheme 1.1): (1) Reaction of free carbenes with suitable copper sources.
51
In
this method, imidazolium salts are deprotonated by a strong base e.g. NaO
t
Bu,
KO
t
Bu, or KH to produce free NHC ligands which are further used to react
with copper sources e.g. Cu(I) halide to obtain Cu(I)-NHC complexes in dry
THF or acetonitrile. (2) Transmetalation from relevant NHC complexes.
52
In
this method, Ag(I)-NHCs are often used as carbene transfer-agents to prepare
Cu(I)-NHC complexes because the Cu-NHC bond is stronger than the
Ag-NHC bond.
53
(3) Alkylation of azolylcuprates.

54
In this method,
Cu(I)-NHC complexes are obtained from alkylation of thiazolyl or
imidazolyl-cuprates complexes formed from the reaction of Cu(I) sources with
lithiated azoles. (4) Direct reaction of imidazolium salts with copper base.
55,56

In this method, reactions of imidazolium halide with Cu
2
O or CuOAc or
copper powder give Cu(I)-NHC complexes. The acidity of the imidazolium
moiety determines the ease of deprotonation of the C-proton by copper base.



4

Scheme 1.1 Preparation methods for Cu(I)-NHC complexes

According to the survey of Lin et al., over 60% of Cu(I)-NHC complexes in
the literature were synthesized from free carbenes and only 22% of
Cu(I)-NHC complexes were synthesized by the Ag-carbene transfer route.
15

Although there are few reports comparing these two methods, Meyer et al.
observed that the Ag-carbene transfer route could give a higher yield than the
free carbene method.
57
The third and fourth methods for the preparation of
Cu(I)-NHC complexes are rarely used.

1.1.2 Structure and Reactivity of Cu(I)-NHC Complexes
There are generally three types of copper NHC complexes: monocarbene
[(NHC)CuX] and [(NHC)CuL]X, dicarbene [(NHC)
2
Cu]X (X = anion) and di-,
tri- and multinuclear copper(I) NHC complexes.

1.1.2.1 Monocarbene Cu(I)-NHC Complexes [(NHC)CuX] and
[(NHC)CuL]X

For [(NHC)CuX]-type complexes, X can be a halide or other coordinating
anion. Among them, [(NHC)CuX] (X = halide) complexes are most important.
Nolan and co-workers prepared a series of [(NHC)CuX] (X = halide)

5
complexes through the free carbene method (examples are given in Fig. 1.1)
with either unsaturated or saturated NHCs.
58
Further studies indicated that
[(NHC)CuX] (X = halide) complexes function not only as catalysts or catalyst
precursors but also as starting materials for synthesis of [(NHC)CuX] (X ≠
halide) or cationic [(NHC)Cu(L)]
+
species.


Fig. 1.1 Structures of [(NHC)CuCl] complexes

For example, [(NHC)Cu(O

t
Bu)] complexes (I-8), which can be obtained from
the reaction of [(NHC)CuCl] (I-7) with NaO
t
Bu
59
, are known to be the active
species in many transformations to yield [(NHC)CuX] (X ≠ halide) or cationic
[(NHC)Cu(L)]
+
species, as outlined in Scheme 1.2. Subsequent reaction of
complexes I-8 with triethoxysilane in the presence of excess 3-hexyne yielded
[(NHC)Cu(vinyl)] complexes (I-9) as the first hydrocupration product.
59,60

Complexes I-8 also react with triethoxysilane to form hydride copper NHCs
(I-10) which are powerful catalysts for the hydrosilylation of ketones.
61


6
[(NHC)CuCl]
[(NHC)CuO
t
Bu]
[(NHC)Cu(CF
3
)]
Cu
NHC

Cu
NHC
Cu
NHC
B
O O
Cu
NHC
O
B(pin)
Cu
NHC
O O
Ph Ph
Ph
B(pin)
Cu
Ph
B(pin)
B(pin)
Cu
Mes O
B(pin)
Cu
[(NHC)CuMe]
([NHC)CuOAc]
AlMe
3
=
B

O
O
pin = pinacolate
= 2,3-dimethyl-2,3-butanediolate
CO
2
(EtO)
3
SiH
Ph
Ph
O
O
C
F
3
S
i
M
e
3
(EtO)
3
SiH
3-hexyne
C
p
L
i
B(pin)

2
Ph
CO
2
, -CO
B(pin)
2
, - OB(pin)
2
Mes
HO
B(pin)
H
Mes
H
O
I-7
I-8I-10
I-9
I-11
I-12
I-13
I-14
I-17
I-15
I-16
I-18
I-19
NHC
NHC

I-20
NaO
t
Bu
H
(NHC)Cu
2
NHC

Scheme 1.2 Reactions of [(NHC)CuO
t
Bu] complexes

Complex I-11, obtained from the reaction of the Cu(I)-NHC complexes with
dibenzoylmethanoate (α,β-diketonate), is an efficient catalyst for the
three-component coupling of electrophilic alkenes, aldehydes and silane.
62

Complex I-12, [(NHC)CuX] (X = cyclopentadienyl), could be prepared by
reacting a [CuCl(NHC)] or [(NHC)Cu(O
t
Bu)]-type species with
cyclopentadienyl lithium.
63
X-ray structures show an η
5
-type bonding mode
for the cyclopentadienyl ligand in I-12. Although saturated NHC complex
[(SIPr)Cu(O
t

Bu)] (SIPr = 1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-

7
2-ylidene) showed high catalytic activity in fluorination reaction, its
unsaturated NHC analogues [(IPr)Cu(O
t
Bu)] (IPr =
1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) recorded low activity.
Through the study of complex I-13, Vicic et al. found out the possible reason
was side reactions occurring on the unsaturated NHC ring backbone.
64
The
carbene boryl copper complexes I-14 were formed from the reaction of I-8
with B(pin)
2
(pin = pinacolate = 2,3-dimethyl-2,3-butandiolate). I-14 can
promote the reduction of CO
2
to CO effectively through the formation of
I-15
65
as well as activate the diboration of alkenes to form complexes I-16.
66

Furthermore, it can serve as the intermediate for the catalysis of hydroboration
of aryl-substituted alkenes promoted by the corresponding copper NHC
complexes. Compound I-17 was formed through the insertion of alkene to the
Cu-boron bond and it can convert to complex I-18 through hydrogen
elimination and re-insertion.
67,68

The mononuclear copper(I) alkyl complex
I-19, [(IPr)Cu(Me)], was obtained from the reaction of I-20 with AlMe
3
and it
was reported to react with substrates possessing N-H, O-H, and acidic C-H
bonds to form neutral type complexes [(IPr)Cu(X)] (X = anilido, phenoxide,
ethoxide, phenylacetylide, or N-pyrrolyl).
69
Such transformations could be
integral to the development of catalytic cycles when metal-mediated
bond-forming reactions are accessible with these and related copper systems.
The results also indicated that the acidity of the X-H bond could be a key
factor, albeit not likely the sole factor, for kinetic accessibility to these
reactions. Based on these results, Gunnoe et al. predicted that inert bonds eg.
arenes and alkanes might be activated by more electrophilic copper NHC
complexes. In subsequent studies, Gunnoe et al. claimed that Cu(I) NHC

8
anilido complexes were more active than Ru(II) anilido complexes in the
traditional SN
2
transformation of bromoethane.
70
In addition, complex I-19
could react with α-borobenzyl alcohol to from complex I-16.

To improve the stability and catalytic selectivity of copper NHC complexes, a
series of mixed donor carbene complexes were studied. Examples are given in
Fig. 1.2. Compound I-21 was prepared by the treatment of a
pyridyl-functionalized imidazolium salt with Cu

2
O and crystallized as a
monomer with the copper center taking up a T-shaped geometry.
55
The Cu-C
and Cu-N distances are 1.880(6) and 2.454(5) Å respectively. Unlike carbonyl
or phosphine ligands, NHCs were initially known to be non-bridging ligands.
This misconception was shattered when the dinuclear copper complex
[Cu
2
I
2
(PCP)] (PCP = (SP-4)-[-1,3-Bis[(R)-1- ((S)-2-diphenylphosphino-P-fer-
rocenyl)ethyl]imidazol-2-ylidene]) (I-22) emerged.
56
Complex I-22, with a
tridentate PCP ligand based on a ferrocene scaffold, was prepared via the free
carbene method with 92% yield while an alternative method involving the
direct reaction of CuOAc with the imidazolium salt [PCPH]I achieved only
54% yield.


Fig. 1.2 Structures of copper NHC complexes with donor side-arm(s)


9
With μ-X (X = H, O, Cl, I), it is easy to form copper monocarbene dinuclear
compounds in solid state. (Fig. 1.3) For example, the first N,S-heterocyclic
carbene (NSHC) copper complex I-23 was prepared via the alkylation method
in 1994.

71
(Scheme 1.3) The X-ray structure of I-23 indicates that the copper
atom bonds to the carbene carbon of the thiazolylidene ligand and the two
bridging chloride atoms in trigonal planar state.


Scheme 1.3 Preparation of copper(I)-NSHC complexes


Fig. 1.3 Structures of copper NHC complexes with μ-X (X = H, O or I)

As shown in Scheme 1.2, the hydride bridged complex I-10 was obtained by
the reaction of [Cu(NHC)(O
t
Bu)] with triethoxysilane.
59
The hydride species

10
are powerful catalysts for the hydrosilylation of ketones and the conjugate
reduction of α,β-unsaturated cyclic enone and ester.
61,72
In practical use, the
hydride can be prepared by one-pot reaction of [CuX(NHC)]-type (X = halide)
complexes with NaO
t
Bu or KO
t
Bu in the presence of silane.
60

NHC ligands
were found to stabilize the Cu(I)-hydride species in lower nuclearity compared
with the phosphine ligands. Complex I-24, with two bridging O
t
Bu groups,
was prepared by the same procedure as that for the mononuclear compound
I-9.
64
(Scheme 1.2) The sterical bulk of N-substituents in [Cu(O
t
Bu)(NHC)]
complex determines the dinuclear or mononuclear formation. Dinuclear
complexes I-25 and I-26 were all prepared via the free carbene route.
73,74
In
complex I-25, the Cu
2
I
2
core is bridged by a dicarbene ligand with short
Cu

Cu (2.663(1) Å) distance and the average Cu-C
carbene
bond length is 1.923
Å. The structure of I-26 consisting of a Cu
3
I
3
core coordinated by three NHCs,

could be viewed as an adduct of [Cu(NHC)I] and a dinuclear [Cu(NHC)I]
2

molecule, resulting in weak copper-copper interactions (Cu
…
Cu 2.635 and
2.658 Å respectively).

1.1.2.2 Dicarbene Cu(I)-NHC Complexes [Cu(NHC)
2
]X
Fig. 1.4 describes some examples for dicarbene copper complexes. For
azolium salts or copper sources with weak coordinating anions such as BF
4
-
or
PF
6
-
, the free carbene method usually yields cationic [Cu(NHC)
2
]
+
species,
instead of neutral [CuX(NHC)] complexes. The first reported dicarbene
copper complex (I-27a) was prepared via the free carbene route.
32
After that, a
series of [Cu(NHC)
2

]
+
species I-27b-d, containing both saturated and
unsaturated NHCs, were subsequently synthesized.
75,76
In order to avoid the

11
steric congestion resulting from the linear arrangement of two NHC ligands on
the copper center, large torsion angle between the two NHCs or long Cu-NHC
bond distance were usually found in these complexes.
15
For example,
compounds I-27b-c have large torsion angles (80°-85°). A long Cu-C
carbene
bond

distance was found in complex I-27d (2.000 Å). More recently, the
analogue of I-27 with asymmetric N,N’-substituents was reported by Albrech
et al.
77
Compound I-28 with a six-membered NHC ring was obtained by the
free carbene route.
78
The distance between the Mes (Mes =
2,4,6-trimethylphenyl) group and the Cu(I) center in the six-membered ring is
significantly shorter than that in five-membered rings, leading to a long
Cu-C
carbene
bond of 1.934(2) Å and a large torsion angle (80.91°) between the

NHC rings. Compound I-29 with a chelating ligand was synthesized by the
Ag-carbene transfer route.
79
The Cu center was coordinated to two NHC rings
twisted at ca. 53.4°. Compound I-30 contains NHCs with a chelating pyridinyl
substituent on N. The carbene ligands remain in a pseudo-trans arrangement
(C-Cu-C 168.5(2)
o
) with weak Cu-N
py
coordination bond (2.310(4) and
2.439(4) Å). A strong deviation of the N-atoms from an ideal 90
o
angle with
respect to the C-Cu-C axis (77.7(2)
o
and 110.4 (2)
o
respectively) leads to a
disphenoidal geometry.
77



12

Fig. 1.4 Structures of dicarbene [(NHC)
2
Cu]
+

species

1.1.2.3 Di-, Tri- and Multinuclear Cu(I)-NHC Complexes
Fig. 1.5 shows both dinuclear and trinuclear copper NHC complexes. The
homoleptic crown complex I-31 was the first reported copper(I) halide
complexes with di(NHC) ligands and it was prepared via the Cu
2
O route.
80

X-ray structural study indicates the two Cu(NHC)
2
moieties are associated
with a Cu
…
Cu contact of 2.553(2) Ǻ. Trinuclear compound I-32 can be
synthesized by both the free carbene route and the Ag-carbene transfer route,
with the latter method giving a better yield (27% vs 56%).
57
X-ray study
indicates that there are three linear NHC-Cu-NHC units and a 3-fold axis
passing through the central carbon atom anchoring three NHC ligands to
exhibit a D
3
-symmetry in the solid state. Compound I-33 was prepared via
Ag-carbene transfer route and each of the copper atom is linearly coordinated
with two carbene centers.
81
DFT calculation revealed the existence of both σ
and π type interactions between the copper atom and the carbenoid carbon.

13
I-31 I-32 I-33
Fig. 1.5 Structures of multinuclear Cu(I)-NHC complexes

Complex I-34 was prepared via Ag-carbene transfer with commercially
available copper powder by Chen‘s group recently.
82
(Scheme 1.4) Direct
reaction of bis(pyrimidylimidazoliumyl)methane dihexafluorophosphate
(H
2
L
2
(PF
6
)
2
) with one equivalent of copper powder in acetonitrile yielded a
dinuclear copper complex (I-35) as dark green crystals. In the presence of
excess copper powder, the green solution of I-35 turns red to form I-34. On
the other hand, I-34 also can be oxidized in air to I-35 reversibly. X-ray
structure establishes that the middle copper atom in compound I-34 is linearly
bound to two NHC carbon atoms with a C-Cu-C angle of 171.7(2)
o
and the
two imidazolylidene rings are twisted by 88.62
o
relative to each other. The two
terminal copper atoms lie in triangular geometry connecting with a carbenoid

carbon atom and a pyridine ring of the same ligand as well as an acetonitrile
molecule. The four Cu-C
carbene
bonds fall in the range of 1.902(5)–1.935(4) Ǻ
and the distance of Cu

Cu is 2.852(1) Ǻ in I-34. However, the Cu
…
Cu
distance shortens to 2.587 Ǻ in I-35 reflecting the formation of a covalent
Cu-Cu bond (the sum of covalent radii of two copper atoms is 2.64 Ǻ).
Cu-C
carbene
bond lengths in complex I-35 are 1.920(8) and 1.932(9) Ǻ
respectively, which is consistent with those of other reported copper carbene
complexes.
83
The two imidazolylidene rings coordinated to the middle copper

14
atom are twisted by 79.64
o
relative to each other.


Scheme 1.4 Preparation of compound I-34

Copper complexes of oligo- or polycarbene ligands are rare. Several examples
are given in Fig. 1.6. Gade and co-workers studied copper(I) complexes
containing NHC with oxazolinyl side arm (I-36a-b) and found that they are

monomeric in solution but aggregate in the solid state.
84
The structure was
effected by substituents (R
1
and R
2
) on the oxazolinyl moiety: a dimeric
structure for [{{2-(4,4-dimethyl)-oxazolinyl-(N-mesityl)imidazoylidene}}-
(bromo)copper(I)]
2
(I-36a) and a coordination polymer with infinite chains for
the chiral derivative [{2-(4-S-isopropyl)-oxazolinyl-(N-mesityl)imidazolylide-
ne}(bromo)copper(I)] (I-36b). The structure of I-37 was found to be
remarkably affected by its solvent, forming a polymer in CDCl
3
, but a dimer
in a mixture of dichloromethane/ether. This is possibly due to its low
solubility in the latter solvent system.
55
The structure of I-38 is similar to that
of I-36b.
85



15

Fig. 1. 6 Structures of polymeric Cu(I)-NHC complexes

Complex I-39 was prepared through free carbene route.
86
Unlike the copper
atoms in complexes I-36-38 which connect to two different carbene ligands to
form (-L-Cu(Br)-L‘-)
n
polymer, each copper atom in complex I-39 connects
with the same carbene ligand resulting in a (-L-Cu-(μ-Br)
2
-Cu-L-)
n
polymer.
As the first example of reversible substrate binding at Cu(I) centers in
Cu–NHCs chemistry, complex I-39 could react with nitrogen bases eg.
N-tert-butylimidazole or piperidine to give the corresponding mononuclear
amine adducts I-40.

1.1.3 Catalytic Activity of Cu(I)-NHC Complexes
Copper NHC complexes exhibit high activity in many reactions. A brief
account on Cu(I)-NHC complexes used in catalysis is presented as follows:


16
1.1.3.1 Carbene Transfer Reactions
Carbene dimerization often occurs in carbene transfer reaction and cannot be
avoided with many different metal catalysts. However, Nolan and co-workers
found that this drawback can be prevented with [(IPr)CuCl] (I-1) as the
catalyst in the reaction of :CHCO
2
Et group (from ethyl diazoacetate) with

unsaturated and saturated substrates (olefins, amine and alcohols) to obtain
very high yields. (Scheme 1.5)
87



Scheme 1.5 Cu(I)-NHC complex catalyzed carbene transfer reaction

1.1.3.2 Cross-Coupling Reactions
Although it is challenging to activate ammonia due to the formation of stable
Werner complexes, the copper NHC complex [(SIPr)CuCl] (I-4) was found to
be an efficient catalyst for the preparation of anilines from ammonia.
88

(Scheme 1.6) Despite a low catalytic activity obtained with electron-rich
substrates, complex [(SIPr)CuCl] still shows good tolerance of different
functional groups such as nitro, cyano, trifluoromethyl, amide and ketone.


17

Scheme 1.6 Cu(I)-NHC complex catalyzed cross-coupling reaction

1.1.3.3 Conjugate Reductions of α,β-unsaturated Carbonyl
Compounds

Conjugate addition of carbonyl compounds could be promoted by copper
NHC complexes.
52,89-91
The combination of catalytic amounts of [(IPr)CuCl]

and NaO
t
Bu with stoichiometric reductant, poly(methylhydrosiloxane)
(PMHS), was found to be an active system for the 1,4-reduction of tri- and
tetrasubstituted α,β-unsaturated esters and cyclic enones.
92
(Scheme 1.7)




Scheme 1.7 Cu(I)-NHC complex catalyzed conjugate reduction

1.1.3.4 Carboxylation Reactions
Carbon dioxide is an attractive, cheap and nontoxic carbon source. However,
the use of CO
2
has

been limited due to its high thermodynamic stability and
low reactivity. Although

Iwasawa and co-workers reported the carboxylation
of aryl- and alkenylboronic esters with CO
2
in the presence of a rhodium(I)
compound and additives, the rhodium catalytic systems show low activity
towards functional groups.
93
Recently, Hou et al. found that the combination

18
of [(IPr)CuCl] with KO
t
Bu can serve as an excellent catalytic system for the
carboxylation of aryl- and alkenylboronic esters with CO
2
to obtain various
functionalized carboxylic acid derivatives in high yield.
94
(Scheme 1.8)


Scheme 1.8 Cu(I)-NHC complex catalyzed carboxylation reaction

1.1.3.5 [3 + 2] Cycloaddition Reactions
Copper complexes have been widely used in reaction of organic azides and
terminal alkynes to prepare 1,2,3-triazoles, known as click reaction.
95
Among
them, copper NHC complexes were found to promote the reaction very
effectively. (Scheme 1.9) For example, Nolan et al. reported that 0.8 mol%
copper NHC complexes could activate both active and inert internal alkynes to
react.
96
[(SIPr)CuCl] was found to promote the reactions to proceed smoothly
at 60 °C but not under ambient conditions, leading to its broad applications as
efficient latent catalysts in this transformation, especially in biology and
material science.
97

More recently, ionic dicarbene copper complex,
[(ICy)
2
Cu]PF
6
(ICy = bis(cyclohexyl)imidazol-2-ylidene), was reported to
catalyze the click reaction effectively with only 40-100 ppm copper loading.
98

Mechanistic studies on the [(NHC)
2
Cu]X system indicated that the high
activity was attributed to one of the NHC ligands on the copper center acting
as a base to deprotonate the starting alkyne to generate a copper acetylide
which triggered the catalytic cycle.


19

Scheme 1.9 Cu(I)-NHC complex catalyzed [3 + 2] cycloaddition reactions

In addition, Chang et al. recently reported the use of [(IPr)CuCl] in the
intermolecular formal [3+2] cycloaddition between terminal alkynes and
α-aryldiazoesters to synthesize indene derivatives under mild condition.
99

(Scheme 1.10)

Scheme 1.10 Cu(I)-NHC complex catalyzed [3 + 2] cycloaddition reactions to
synthesize indene derivatives

1.1.3.6 Hydrosilylation Reactions
Hydrosilylation is one of the important reactions catalyzed by copper NHC
complexes.
100,101
Nolan et al. screened the activity of cationic di-NHC
complexes in the hydrosilylation of ketones and found that the catalytic
performance was affected by both the ligand and the counterion. (Scheme
1.11) Moreover, the cationic species, [Cu(NHC)
2
]
+
proved to be more efficient
than its neutral monocarbene counterparts, [(NHC)CuCl], under similar
reaction conditions for most cases.
75,76
Mechanistic studies by
1
H-NMR
indicated that one of the NHC ligands in [Cu(IPr)
2
]
+
BF
4
-
was replaced by
t
BuO from NaO
t

Bu in the activation step to produce the neutral
[Cu(O
t
Bu)(IPr)] complex (I-24) which is known to be a direct precursor of an
copper NHC hydride as the actual active species in this transformation.

20

Scheme 1.11 Cu(I)-NHC complex catalyzed hydrosilylation

1.3.7 Hydroboration Reactions
Hoveyda and co-worker reported the use of a readily available copper NHC
complex [(SIMes)CuCl] (SIMes = 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydro-
imidazol-2-ylidene) (I-5) in catalytic boron-copper addition to acyclic and
cyclic aryl olefins to obtain >98:<2 site selectivity.
102
(Scheme 1.12) This
catalytic activity is comparable to those obtained through transformations with
borohydride reagents catalyzed by Rh- and Ir-based catalysts.
103,104
For chiral
copper NHC complexes, high enantioselectivities [enantiomeric ratio (er)
values up to 99:1] were achieved. Due to the superior activity of the more
strongly σ-donating Cu-NHC systems, NHC complexes are more effective
than phosphine-based system in this reaction.


Scheme 1.12 Cu(I)-NHC complex catalyzed hydroboration reaction

1.3.8 Other Applications of Cu(I)-NHC Complexes

Besides the reactions described above, Cu(I)-NHC systems have also been

21
applied in a wide range of homogeneous catalytic reactions, such as
cyclopropanation over C-H insertion
87,105
, trifluoromethylation,
64

Ullmann-Arylation reaction,
106
conjugate addition

of carbonyl aziridination of
aliphatic alkenes,
107
oxidative carbonylation of amino
108
etc. In addition,
Cu(I)-NHC systems may find industrial applications, such as in the reduction
of CO
2
to CO
65,109
, hydrogen storage
110
and other medical applications
111
.

1.2. Gold(I)/(III) N-Heterocyclic Carbene Complexes
1.2.1 General Synthetic Methods for Au(I)/(III)-NHC
Complexes
Five strategies have been developed for the preparation of Au(I)-NHC
complexes (Scheme 1.13)
15,112
: (1) Reaction of Au(I) sources with free NHCs.
In this method, free NHCs can be isolated or prepared in situ by reacting
azolium salts with a base such as NaO
t
Bu, KO
t
Bu, Na
2
CO
3
, etc. (2) Transfer
of NHCs from group 6, 7 and 11 metal complexes. In this method,
Ag(I)-NHCs are the most popular transfer-reagent, and group 6 and 7
metal-NHCs are rarely utilized. (3) Protonation or alkylation of gold
carbeniate compounds. In this method, Au(I)-NHC complexes are formed by
the reaction of Au(I) sources with lithiated azoles followed by protonation or
alkylation. The known complexes are mainly those with thiazolyl NHC
ligands. (4) Insertion of a gold atom into electron rich double bonds. In this
method, [AuCl(PPh
3
)] is often used to react with electron-rich olefins at
100 °C to produce Au(I)-NHC complexes. (5) Nucleophilic addition to
Au(I)-coordinated isocyanide ligands.

22

Scheme 1.13 Au(I)-NHC complexes formation

According to the survey of Lin et al., over 70% of the published Au(I)-NHC
complexes were synthesized through the Ag-carbene transfer route, and only
20% was obtained through the free carbene route, which is in contrast to
copper NHC complexes preparation.
15


Compared to Au(I)-NHC complexes, very few works on Au(III)-NHCs were
reported. There are four methods developed for Au(III)-NHC complexes
preparation
15,112
: (1) Oxidative addition of halogens to Au(I)-NHC compounds.
(2) Transfer of NHCs from group 6 metal compounds to a Au(III) source. (3)
Cyclization of Au(III)-coordinated isocyanide ligands. (4) Reaction of Au(III)
source with free carbene.

1.2.2 Structure and Reactivity of Au(I)/(III)-NHC Complexes
Unlike Cu(I)-NHC complexes with several coordination modes (two-,
three- and four-coordination modes), Au(I)-NHC complexes only exhibit
two-coordination mode and Au(III)-NHC complexes exhibit

23
four-coordination mode. Au(I)-NHC complexes are discussed below,
according to the three categories: monocarbene [AuX(NHC)] and
[Au(NHC)L]X, dicarbene [(NHC)
2

Au]X, and di- and multinuclear gold
NHC complexes.

1.2.2.1 Monocarbene Au(I)-NHC Complexes [AuX(NHC)] and
[Au(NHC)L]X
Although Ag-NHC transfer is the powerful method for Au(I)-NHC complexes
preparation, neutral [AuX(NHC)] (X = Br or I) complexes cannot be prepared
via the direct reaction of [AuCl(SMe
2
)] with [AgX(NHC)] (X = Br or I) due to
the formation of [AuCl(NHC)] instead of [AuBr(NHC)] or [AuI(NHC)]
species. Examples of [AuCl(NHC)] complexes containing imidazol-2-ylidene
with symmetrical or asymmetrical N,N’-substituents and saturated
imidazol-2-ylidene with symmetrical N-substituents are shown in Fig.
1.7.
41,113
These complexes not only serve as catalysts/precatalysts but also as
starting materials in the formation of [(NHC)AuX] (X ≠ Cl) and cationic
[(NHC)AuL]
+
species, as outlined in Scheme 1.14.

Fig. 1.7 Structures of [(NHC)AuCl] complexes

24
The bromide and iodide complexes II-2 were obtained via the reaction of
[AuCl(NHC)] with suitable alkali metal bromide or iodide salts (LiBr, KI,
etc.), similar to the procedure used for preparation of [AuX(NHC)] (X = SCN,
SeCN, CN) complexes.
114

[Au(pseudohalide)(NHC)] compounds (II-3) were
synthesized by the reaction of silver pseudohalide salts with
[AuCl(NHC)].
114-116
However, Au(I)-NHC fluoride complex (II-4) could not
be obtained with these two methods above. It was prepared via reacting
[Au(O
t
Bu)(NHC)] with Et
3
N·HF.
117
Complexes II-5a-5e, with a thioglucose
derivative as L, were prepared from the reaction of [AuCl(NHC)] with HL in
the presence of a base.
118,119
Complex II-6a, with a saccharin anion, was
obtained by reacting the corresponding [AuCl(NHC)] with a sodium saccharin
salt in the presence of AgPF
6
.
119
[(NHC)AuX] (X = N
3
, NCO, etc.) complexes
were similarly prepared.
114
Compounds II-7 and II-8 were obtained from the
reaction of corresponding [(NHC)AuCl] compounds with [(HC≡C)MgCl] and
[Mg(CH

3
)
2
] respectively.
114
Two interesting [(NHC)Au(fluoroviyl)]
compounds, II-9a and II-9b, were obtained by reacting the [AuF(NHC)]
compound with unactivated alkynes of 3-hexyne and 1-phenyl-1-propyne
respectively as the intermediate for hydrofluorination of alkynes.
120



25
N
N
R
R
Au X
N
N
Dipp
Dipp
Au L
N
N
R
R
Au X
II-6a

II-3a
t
Bu OAc
II-3b
t
Bu ONO
2
II-3c Dipp NTf
2
II-9a L = EtC=CEtF
II-9b L = PhC=CCHF
N
N
Au X
R
R
N
N
t
Bu
t
Bu
Au
O
OAc
AcO
AcO
OAc
S
N

N
R
R
Au X
II-5a R = Me
II-5b R =
i
Pr
II-5c R = Bu
II-5d R = Cy
II-5e R = Dipp
HX, base
N
S
O
O
O
X =




A
g
P
F
6

/

N
a
X
o
r

A
g
N
O
3

/

K
X
R
2
R
2
X = Cl
Mg(C CH)Cl
Mg(CH
3
)
2
II-8
II-7
R = Dipp,
II-6b R =

t
Bu, X = N
3
,
II-6c R =
t
Bu, X =NCO,
MX
M = Li, Na, K
N
N
t
Bu
Au X
X = Br, I, SCN, SeCN, CN
t
Bu
II-1
II-2
II-3
N
N
t
Bu
t
Bu
Au Me
1
)

N
a
O
t
B
u
2
)

E
t
3
N
,

H
F
N
N
Dipp
Dipp
Au F
II-4
A
g
X
R X
=X
Scheme 1.14 Reactions of [(NHC)AuCl] complexes

Fig. 1.8 shows cationic [(NHC)AuL]
+
species, in which the non-NHC ligand L
is neutral. Compound II-10, with a strong coordinating ligand PPh
3
, was
synthesized by directly reacting a [AuCl(NHC)]-type compound with PPh
3
in
the presence of KPF
6
in CH
2
Cl
2
.
118
By changing the silver salt and solvent to
AgBF
4
and EtOH, homoleptic [Au(NHC)
2
]
+
and [Au(PPh
3
)
2
]
+

species were
obtained, instead of the expected [(NHC)Au(PPh
3
)]
+
species. This is possibly
because AgBF
4,
as a good Cl
-
sponge, prefers the formation of
thermodynamically more stable complexes. Compound II-11 with acetonitrile
ligand was prepared by the reaction of [AuCl(NHC)] with weakly
coordinating silver salt eg. AgBF
4
and AgPF
6
in acetonitrile.
121
A saturated
NHC complex II-12 with a Au-alkyne moiety was synthesized by treating the
corresponding [AuCl(NHC)] with AgBF
4
and 3-hexyne.
120