N-Heterocyclic carbenes: deducing σ- and π-contributions in Rh-catalyzed hydroboration and Pd-catalyzed coupling reactions

Article abstract of DOI:10.1016/j.tet.2008.04.030

The effect of tuning the electronic properties of N-heterocyclic carbene (NHC) ligands was evaluated in multiple, mechanistically distinct, metal-mediated reactions. Hydroboration and Heck reactions, catalyzed by Rh-NHC and Pd-NHC complexes, respectively,

Full text of DOI:10.1016/j.tet.2008.04.030

Tetrahedron 64 (2008) 6853–6862
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
N-Heterocyclic carbenes: deducing s- and p-contributions in Rh-catalyzed
hydroboration and Pd-catalyzed coupling reactions
y
Dimitri M. Khramov, Evelyn L. Rosen, Joyce A.V. Er, Peter D. Vu , Vincent M. Lynch,
*
Christopher W. Bielawski
Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, TX 78712, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
The effect of tuning the electronic properties of N-heterocyclic carbene (NHC) ligands was evaluated in
multiple, mechanistically distinct, metal-mediated reactions. Hydroboration and Heck reactions, cata-
lyzed by Rh–NHC and Pd–NHC complexes, respectively, were found to result in yields that were up to ten
Received 1 February 2008
Received in revised form 4 April 2008
Accepted 8 April 2008
times lower when
analogues bearing
p
-withdrawing substituents were incorporated into the NHC backbone relative to
Available online 11 April 2008
s
-withdrawing groups.
Dedicated to Professor John F. Hartwig in
honor of his receipt of the 2007 Tetrahedron
Young Investigator Award
Ó 2008 Elsevier Ltd. All rights reserved.
1
. Introduction
NHC–metal complexes.8 For example, in Pd-mediated coupling
reactions, NHC ligands bearing bulky N-substituents have been
found to drastically increase the stabilities and activities of the
Over the past 40 years,1 N-heterocyclic carbenes (NHCs) (1)2
13
have blossomed into a class of ligands that have proven to be useful
for a broad range of transition metals. As strong, two-electron
donors, they generally coordinate to metals in a fashion that is
analogous to phosphines; however, in many instances, they often
produce complexes which are more thermally-stable and/or ex-
catalytically pertinent species. Likewise, in NHC-ligated pre-cata-
lysts, bulky NHCs have been shown to promote the dissociation of
3
,4
14
ancillary ligands and facilitate catalyst formation. This feature is
nicely exemplified in Ru-based olefin metathesis catalysts con-
5
6
4e,15
taining sterically encumbered NHC and phosphine ligands.
3
hibit higher catalytic activities. Prime examples include the
Collectively, a broad range of highly active catalysts has resulted
from judicious modification and optimization of the steric param-
7
8
Grubbs second generation (2) and PEPPSI catalysts (3) (see Fig. 1),
both of which show higher catalytic activities in olefin metathesis
and cross-coupling reactions, respectively, than many of their
phosphine-ligated counterparts. Considering the number of syn-
thetic methods known to prepare these compounds, NHCs are
often the ligand of choice for applications ranging from metal-
3
eters of NHCs.
Tuning the electronic components of NHCs is also of great
interest for enhancing the catalytic activities of NHC–metal com-
9
16
plexes. Most NHC frameworks offer three distinct options for such
17
purposes: (1) transposition of heteroatoms (e.g., imidazole/
3
,10
mediated catalysis to organometallic materials.
oxazole or thiazole), (2) incorporation of additional heteroatoms
18
In view of this breadth of utility, substantial efforts have been
directed toward understanding the nature of the interactions
formed between NHCs and transition metals. Like many other li-
gands,11 both the steric and electronic components of NHCs can be
independently modulated. Sterics are often modified by varying the
N-substituents using relatively straightforward processes that
typically involve standard alkylation or amination chemistries. In
many cases, the size of the NHC’s N-substituents has been shown to
significantly influence the catalytic activities of their respective
into the backbone, and (3) attachment of pendant electron-do-
16
nating or electron-withdrawing groups. With rare exception,
varying the N-substituents (particularly, N-aryl substituents)
i-Pr
i-Pr
Mes
Ad
N
N Mes
Cl
N
N
12
N
N
i-Pr
i-Pr
Ad
Ru
Cl Pd Cl
Cl
Ph
1
PCy
2
3
N
Cl
3
*
Corresponding author. Tel.: þ1 512 232 3839; fax: þ1 512 471 8696.
E-mail address: bielawski@cm.utexas.edu (C.W. Bielawski).
Undergraduate contributor.
Figure 1. Representative examples of an N-heterocyclic carbene (NHC) (1) and cata-
lytically active transition metal complexes bearing NHCs (2 and 3). Ad¼adamantyl,
Mes¼2,4,6-trimethylbenzene, i-Pr¼iso-propyl.
y
0
040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.04.030

6854
D.M. Khramov et al. / Tetrahedron 64 (2008) 6853–6862
N
N
their respective transition metal complexes, the nature of these
L =
N
N
26
O
effects has not been studied in detail. For example, NHCs are
known to form - and -bonding interactions with metals. Because
Ph
Ph
Cy
Ph
s
p
4
5a
L
νCO = 2020 cm-1
1990 cm-1
the lone pairs on the nitrogen atom were believed to fill the empty
p-orbital of the flanking carbene atom in preference to any ligated
Cl Rh CO
CO
transition metal, p-backbonding interactions have historically been
N
N
N
27
N
Mes
Mes
considered to be negligible. However, that view has changed
considerably over the past several years. For example, Meyer,
Frenking, and others employed a combination of computational
Cy
5
b
5c
976 cm-1
2004 cm-1
1
and crystallographic studies to conclude that
p-backbonding in-
Figure 2. Representative complexes used for examining the electron-donating prop-
erties of N-heterocyclic carbenes. The number listed below each NHC refers to the
teractions contribute up to 30% of the overall bonding character
formed between NHCs and certain transition metals. More re-
cently, our group synthesized and characterized a series of Rh olefin
28
stretching frequency
(
CO
n )
exhibited by the trans-CO group in their respective
2
0–22
(
NHC)RhCl(CO) complexes.
2
Ph¼phenyl, Mes¼mesityl, Cy¼cyclohexyl.
and carbonyl complexes bearing NHCs with different
s- and p-
withdrawing groups. Using NMR and FTIR spectroscopies, we were
able to separate their relative electronic effects, which lead us to
generally has little effect on the electronic properties of NHCs.
Regardless, NHC electronics can often be modified without dis-
rupting steric features, which effectively enables separation of
these two key components.
The electronic properties of NHCs, particularly their electron-
donating abilities, are routinely quantified by measuring the CO
conclude that
NHC–Rh complexes but, in some cases, tunable.
Poised by these results, we sought to build upon Organ’s initial
investigation and gain insight into how various - and -contrib-
p-backbonding interactions were not only present in
2
9
s
p
utors influence the catalytic activities of NHC–metal complexes.
Herein, we compare the abilities of a series of Rh- and Pd-com-
plexes bearing uniquely functionalized NHCs to facilitate hydro-
boration and coupling reactions, respectively. We believe our
stretching frequencies (
bonyl complexes, (NHC)RhX(CO)
that the largest changes in the electron-donating abilities of NHCs
are achieved by incorporating one or more heteroatoms into their
backbones. For example, a Rh carbonyl complex bearing an oxa-
nCO) exhibited by their respective Rh car-
19
2
(X¼Cl, I). Current data indicates
results show that both s- and p-interactions are formed between
ꢀ
1
NHCs and transition metals and, in cases where one interaction
dominates, can significantly influence the yields and outcomes of
reactions catalyzed by such complexes. On a broader level, the re-
sults obtained from this fundamental investigation should help
create new design parameters for optimizing reactions catalyzed by
metal complexes containing NHC-type ligands.
diazolylidene (4; see Fig. 2) exhibited a
corresponds to the CO ligand trans to the NHC and is among highest
n
CO¼2020 cm , which
2
0
known frequencies for these types of complexes. While in-
corporation of additional heteroatoms into NHC scaffolds likely
changes their electronic structures with respect to typical imida-
zolylidenes, changes in sterics may contribute as well. For example,
recent reports revealed that varying the ring size of NHC-type li-
21
gands (i.e., 5a/5b/5c) had substantial effects on the
n
CO
2. Results and discussion
2
2
exhibited by their respective Rh carbonyl complexes. Hence, to
properly study the effects of modifying the electronic components
of NHCs, all other structural components should remain identical.
Adhering to this criteria, Organ and co-workers prepared a
series of 1,3-diadamantyl-benzimidazolylidene precursors that
differed only in the functional groups present at the distal 5- and 6-
positions.23 They then studied the ability of their respective NHCs
to facilitate Pd-mediated Suzuki–Miyaura cross-coupling re-
2.1. Synthesis and characterization of Rh complexes ligated
to electronically different NHCs
In our previous study,29 we prepared a series of Rh olefin (6) and
carbonyl (7) complexes ligated to 1,3-dimethylimidazolylidenes
bearing various functional groups in their 4- and 5-positions
(see Fig. 4). We benchmarked 1,3-dimethyl-4,5-dichloroi-
midazolylidene as an NHC possessing predominately s-with-
drawing groups. However, due to known ortho-, para-directing
2
4
actions between various aryl chlorides and boronic acids (see
2
3
Fig. 3). This particular reaction was chosen because it is fairly well
0
accepted that its rate-limiting step is oxidative addition of Pd
effects of halo substituents in electrophilic aromatic substitutions
2
5
species with aryl chlorides; hence, ligand electronics should
strongly influence the outcomes of these reactions. As expected,
complexes bearing electron rich 5,6-dimethoxy-benzimidazolyli-
denes were generally found to give higher yields of product than
their electron deficient 5,6-difluoro analogues over the same time
periods. This seminal contribution effectively paved a new avenue
for tuning the activity of Pd-catalysts bearing NHC ligands.
(EAS), the
counteract, at least partially, their
der to strengthen our hypothesis that
p
-donor abilities of the Cl substituents in this NHC may
-withdrawing character. In or-
-backbonding interactions
s
p
are operative in NHC–Rh complexes and to ensure that the
previously observed electronic effects were not due to weakened
s
-donation, Rh olefin and carbonyl complexes ligated to 1,3-di-
methyl-4-trifluoromethylimidazolylidene were prepared and
studied. This particular NHC derivative was chosen because CF and
While the installation of pendant functional groups onto NHC
ligands clearly influences the electronic and catalytic properties of
3
CH3
CH3
R1
R2
R1
R2
Cl
CO
Ad
N
N
X
X
N
N
Rh
Cl
Rh CO
Cl
N
CH3
N
CH3
B(OH)2
CH3
Cl
Ad
Pd(OAc)2
Cs CO
1
1
1
1
1
2
1
1
1
1
1
2
H3C
OCH3
6- H:
-Cl:
-CF3:
-NO2:
R
R
R
R
R
= R = H
= R = Cl
= H; R = CF3
= H; R = NO2
7- H:
7-Cl:
7-CF3:
7-NO2:
R
= R = H
= R = Cl
= H; R = CF3
= H; R = NO2
2
3
2
2
6
6
6
6
R
R
R
R
dioxane, 80 °C
X = OCH , 83%
3
2
2
OCH3
X = H, 72%
X = F, 53%
2
2
2
2
-CN:
= R = CN
7-CN:
= R = CN
Figure 3. Previously reported Suzuki–Miyaura cross-coupling reactions using Pd
complexes ligated to electronically different N-heterocyclic carbenes (generated in
situ).
Figure 4. Structures of Rh olefin (6) and carbonyl (7) complexes synthesized and ex-
amined in this study.
2
3a

D.M. Khramov et al. / Tetrahedron 64 (2008) 6853–6862
6855
Table 1
2.2. Deducing
reactions catalyzed by Rh–NHC complexes
s- and p-contributions in hydroboration
Spectroscopic properties of various NHC–Rh complexes
(]CH)a (ppm)
Complex
n
CO (cm
b
ꢀ1
)
Complex
d
With a range of Rh complexes ligated to various functionalized
NHCs in hand, attention turned toward exploring their abilities to
catalyze hydroboration reactions. The hydroboration of terminal
alkynes yields alkenylboronates, which ultimately provides direct
6
6
6
6
6
-H
-Cl
-CF
-NO
-CN
5.00
5.03
5.06
5.12
5.17
7-H
7-Cl
7-CF
3
7-NO
7-CN
2004
2010
2006
2012
2017
3
2
2
access to vinyl boranes, a synthetically useful class of com-
a
Chemical shifts were determined using 1H NMR spectroscopy (solvent¼CDCl
3
),
24
pounds.
Although this reaction proceeds uncatalyzed under
reported downfield to tetramethylsilane and referenced to residual protio solvent.
3
2
33
b
certain conditions, advantages of known catalyzed variations
include decreased reaction times and unique selectivities. In par-
ticular, Rh-catalyzed hydroborations of terminal alkynes with
pinacol or catecholboranes were shown to be greatly facilitated by
phosphine ligands and often provided (Z)-1-alkenylboronates in
Carbonyl stretching frequencies (
for compounds in solution (CDCl
). Values reported are ꢂ0.5 cm . The frequency
indicated corresponds to the trans-CO moiety.
nCO) were determined using FTIR spectroscopy
ꢀ
1
3
NO
2
groups possess identical group electronegativities (3.4).30,31
34
high yields. Since NHC ligands have been shown to have similar
metal-activating properties as phosphine ligands,
Hence, while the electron-withdrawing capabilities of these two
functional groups are virtually equal, they can be distinguished by
1–5
we explored
the ability of analogous NHC–Rh complexes to catalyze various
hydroboration reactions. In addition, NHC ligands bearing different
the fact that CF
are meta directors in EAS reactions).
Rh complex 6-CF was prepared in accord with our previously
reported protocol.29 1,3-Dimethyl-4-trifluoromethylimidazolium
iodide was treated with Ag O followed by transmetallation using
Rh(cod)Cl]
(cod¼1,5-cis-cis-cyclooctadiene) to obtain pure 6-CF
as a yellow solid in 95% yield. Subsequently, pressurizing the so-
lution of 6-CF with carbon monoxide afforded Rh complex 7-CF
3
groups exhibit minimal p-interactions (i.e., they
functional groups were probed to deduce how
s- and p-contri-
3
butions formed between NHCs and Rh influenced the outcomes of
these reactions.
2
Initial efforts were directed toward studying the hydroborations
of phenylacetylene and 1-octyne using pinacolborane and Rh olefin
complexes 6. In general, the reactions were performed under
[
2
3
34
3
3
conditions analogous to those reported by Miyaura. Mixtures of
1
in quantitative yield. Analysis of these complexes using H NMR
and FTIR spectroscopies revealed that key signals were in accord
with analogues bearing pendant H and Cl groups (see Table 1).
Furthermore, despite the identical electronegativities of tri-
pinacolborane (1.0 equiv), alkyne (1.2 equiv), Rh catalyst (3 mol %),
and an excess of triethylamine (5 equiv) were prepared in THF at
ꢁ
1
2
5 C and then monitored over time by H NMR spectroscopy using
an internal standard (mesitylene or 1,3,5-trimethoxybenzene). As
control experiments, uncatalyzed hydroborations, as well as those
catalyzed with [Rh(cod)Cl] , were also performed under otherwise
2
similar conditions. The results of these reactions are summarized in
Table 2.
fluoromethyl and nitro groups, 6-CF
troscopic properties that were significantly different than 6-NO
and 7-NO , respectively. In addition, the solid-state structure of 6-
CF (shown in Fig. 5) revealed bond distances that were similar to
those found in the solid-state structures of 6-H and 6-Cl (not
shown). For example, the distance of Ccarbene–Rh in 6-CF was
found to be 2.018(4) Å, which is similar to Ccarbene–Rh distances of
.023(2) and 2.021(2) Å exhibited by 6-H and 6-Cl, respectively. For
comparison, the solid-state structures of 6-NO and 6-CN revealed
3 3
and 7-CF exhibited spec-
2
2
3
As shown in entry 1, Rh complex 6-H was found to catalyze the
hydroboration of phenylacetylene, affording a 55% yield of product,
3
35
under the aforementioned conditions. To the best of our knowl-
2
edge, this is the first example demonstrating that Rh–NHC com-
36
2
plexes are capable of catalyzing hydroboration reactions.
shorter Ccarbene–Rh distances of 2.005(3) and 2.006(6) Å, re-
spectively. Collectively these results provide additional support for
our notion that
Rh complexes and may be tuned through derivatization of the
NHC. Moreover, we believe that by comparing metal complexes
ligated to NHCs bearing trifluoromethyl groups to those with nitro
3
Complexes 6-Cl and 6-CF afforded slightly lower yields of products
compared to 6-H (see entries 2 and 3), which suggested to us that
the Rh center was not strongly influenced by NHCs bearing strong
p-backbonding interactions are operative in NHC–
s
-withdrawing groups. In contrast, significantly lower yields of
product were obtained when 6-NO or 6-CN complexes, which
contain NHCs bearing -withdrawing groups, were used as cata-
lysts (see entries 4 and 5). It is noteworthy that the yield of the
reaction catalyzed by 6-CF was nearly twice than that of the re-
action catalyzed by 6-NO . As mentioned above, the NHCs in these
2
9
2
p
groups should enable (1) a means to separate s- and p-interactions
formed between NHCs and transition metals and (2) insight into
how each of these fundamental contributors influence the catalytic
activities exhibited by these complexes.
3
2
catalysts bear functional groups with identical group electronega-
tivities; hence, we surmise that the observed difference in yields for
these two complexes is due to differences in the nature of the in-
teraction (
of the Rh–NHC complexes examined catalyzed hydroborations
significantly more efficiently than [Rh(cod)Cl] or those performed
s vs p) formed between the NHC and Rh. Importantly, all
2
without any added catalyst (cf., entries 6 and 7, respectively), which
gave very low yields of product under otherwise identical condi-
tions. Collectively, these results indicate, for the first time, that Rh
complexes containing NHCs with s-withdrawing groups can lead
to different product outcomes than analogues bearing
drawing groups.
p-with-
Considerably different reaction outcomes were observed for
hydroborations of 1-octyne catalyzed by the same set of Rh–NHC
complexes. As shown in Table 2, preliminary experiments sug-
gested that while 6-H was capable of catalyzing the hydroboration
of this substrate under the conditions described above, relatively
ꢁ
Figure 5. ORTEP drawing of 6-CF
2
3
. Selected bond lengths (Å) and angles ( ): C1–Rh1,
3
5
low yields of product were obtained (see entry 8). Comparison of
.018(4); C1–N1, 1.359(6); C1–N2, 1.353(3); N1–C2, 1.393(5); N2–C3, 1.373(5); C2–C3,
1.349(6); N1–C1–N2, 104.4(4).
entries 8–12 revealed that Rh complexes 6 afforded virtually the

6856
D.M. Khramov et al. / Tetrahedron 64 (2008) 6853–6862
Table 2
O
a
O
O
Hydroboration of alkynes catalyzed by various Rh complexes
B
Rh(NHC)(Cl)Ln
A
B H
R
Bpin
R
O
Rh cat. (3 mol%)
R
HBpin
reductive
elimination
X
oxidative
addition
Y
Et N, THF, 25 °C
3
R
Bpin
Y
X
Entry
R
Rh catalyst
Yieldb (%)
E/Z/Tc
N
O
N
N
N
O
O
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
Ph
Ph
Ph
Ph
6-H
6-Cl
55
42
50
24
24
9d
0
1.5:0.8:1.0
1.3:0.0:1.0
1.3:0.2:1.0
1.4:1.0:1.0
1.5:0.0:1.0
2.2:1.1:1.0
nd
3.8:1.4:1.0
4.5:1.5:1.0
4.1:1.5:1.0
3.8:0.9:1.0
3.8:2.0:1.0
4.8:0.0:1.0
nd
4.5:1.6:1.0
4.3:0.7:1.0
1.4:0.7:1.0
1.3:0.4:1.0
1.3:0.3:1.0
1.5:0.2:1.0
1.4:0.3:1.0
1.2:0.3:1.0
1.9:0.8:1.0
1.7:0.4:1.0
1.2:0.4:1.0
B
Rh Cl
B Rh Cl
6-CF
3
O
H
H
B
6-NO
6-CN
2
D
R
X
Y
[Rh(cod)Cl]
None
6-H
2
N
N
O
O
R
n-Hex
n-Hex
n-Hex
n-Hex
n-Hex
n-Hex
n-Hex
Ph
n-Hex
4-MeO–Ph
4-NO –Ph
4-CN–Ph
4-MeO–Ph
27
28
hydride
migration
B
Rh Cl
H
alkyne
coordination
6-Cl
d
1
0
6-CF
3
21
18
21
10
d
d
1
1
6-NO
6-CN
2
R
1
2
C
d
1
3
[Rh(cod)Cl]
None
(IMes)Rh(cod)Cl
2
1
4
0
26
50
60
30
33
43
17
32
31
20
28
Figure 6. Proposed general reaction mechanism for the hydroborations of alkynes
catalyzed by Rh–NHC complexes.
1
5
1
6
(IMes)Rh(cod)Cl
1
7
6-H
6-H
6-H
1
8
2
1
9
migration (C/D), and (4) reductive elimination, ultimately leading
to an alkenylboronate product and A. The structures of the in-
termediates shown in Figure 6 are supported by analogous Ir
hydride and Ir alkyl complexes bearing phosphine ligands, most
of which have been characterized spectroscopically or
20
6-CF
6-CF
6-CF
3
3
3
2
1
2
4-NO –Ph
4-CN–Ph
4-MeO–Ph
4-NO
22
23
24
25
6-NO
6-NO
6-NO
2
2
2
2
–Ph
4-CN–Ph
4
1,42
crystallographically.
cod¼1,5-cyclooctadiene; IMes¼1,3-dimesitylimidazolylidene; nd¼not determined.
While each of the steps in the proposed mechanism should be
influenced by the electron density residing at the metal center, and
therefore amenable to modulation by the coordinated NHC, it has
been previously proposed that reductive elimination is the rate-
a
General conditions: [pinacolborane]
5.0 equiv), [alkyne]
0
¼0.33 M (1.0 equiv), [Et
3
N]
0
¼1.65 M
ꢁ
(
0
¼0.4 M (1.2 equiv), Rh complex (3 mol %), THF, 14 h, 25 C,
unless otherwise noted. All reactions were performed in triplicate.
b
Combined yield of all possible isomers, as determined from 1H NMR analysis of
crude reaction mixtures using an internal standard (mesitylene or 1,3,5-trime-
39a,41,42
limiting step in Rh-catalyzed hydroborations of alkenes.
thoxybenzene). Unless otherwise noted, reported yields are ꢂꢃ5%.
c
Based on the data shown in Table 2, we surmise that reductive
elimination is also the limiting step for hydroboration of alkynes
catalyzed by the Rh–NHC catalysts described herein. In particular,
intermediate D features an NHC ligand situated trans to the alkenyl
moiety. Electron-withdrawing groups on the carbene ligand are
positioned to remove electron density from Rh, resulting in
a stronger bond formed between the alkene carbon and the metal
center. Hence, reductive elimination should be inhibited and result
in decreased yields of product in accord with the nature and
strength of the electron-withdrawing group. Indeed, as shown for
phenylacetylene in Table 2, a Rh catalyst bearing an electron rich
NHC ligand generally afforded higher yields of products than its
electron deficient analogues (cf., entry 1 vs entries 2–5). Moreover,
the nature of the interaction formed between NHCs and Rh appears
Average ratios of the olefin regioisomers found; E: trans, Z: cis, T: terminal.
Yield is ꢂꢃ8%.
d
same yield of product, within experimental error, regardless of the
functional group installed on the NHC ligand. Furthermore, the
activities of these Rh–NHC complexes were found to be only mar-
2
ginally more active than [Rh(cod)Cl] (entry 13). Hence, any in-
fluence caused by the pendant functional groups on the NHC
ligands in 6 appeared to have only a minimal effect on the perfor-
mance of these particular hydroboration reactions. More broadly,
this result suggested to us that the importance of relative s- and p-
contributions to the interactions formed between Rh and NHCs
may be substrate dependent.
Although Rh complexes bearing bulky phosphine ligands have
been reported to afford hydroboration products with high cis
contents, very modest stereoselectivities were generally observed
to play an important role. Catalysts ligated to NHCs bearing
withdrawing CF groups afforded higher yields of product com-
pared to analogues bearing -withdrawing NO or CN groups (cf.,
entry 3 vs entries 4–5). These results suggested to us that
-withdrawing groups on the NHC ligand are more effective at
decreasing electron density at the Rh center and therefore more
significantly influencing its reactivity when compared to analogues
bearing s-withdrawing groups.
To gain additional support for the notion that reductive elimi-
nation is the rate-determining step in Rh–NHC catalyzed alkyne
hydroborations, a series of functionalized phenylacetylene de-
rivatives were synthesized and studied for their ability to react with
pinacolborane under the conditions described above (entries 17–
25). Using 6-H as a catalyst, higher yields of hydroboration product
were obtained when phenylacetylene (entry 1) or 4-methoxy-
phenylacetylene (entry 17) were used as substrates when com-
pared to analogous reactions performed using relatively electron
deficient alkynes, i.e., 4-nitro- or 4-cyanophenylacetylene (entries
18 and 19, respectively). In the former cases, the increased electron
s-
3
p
2
3
4
in the aforementioned hydroboration reactions catalyzed by 6.
However, this disparity may, at least partially, be explained by the
difference in sterics between the NHCs explored herein (which
contain relatively small N-methyl groups) and the bulky phos-
p
3
4
phines (i.e., PCy
by the observation that (IMes)Rh(cod)Cl (IMes¼1,3-dimesitylimi-
dazolylidene),37
complex that bears bulky N-substituents,
3
) previously used. This hypothesis is supported
a
exhibited different selectivities, when compared to 6-H, for the
hydroboration of both phenylacetylene and 1-ocytne (cf. entries 1
and 8 vs 15 and 16, respectively).
Based on a proposed mechanism of Rh-catalyzed hydroboration
3
8
of alkenes, as reported by M a¨ nnig and N o¨ th and later supported
by others,3
9,40
an analogous mechanism for the hydroboration of
alkynes is proposed in Figure 6. There are four key steps in this
mechanism: (1) oxidative addition of a borane to Rh–NHC catalyst
A, (2) alkyne coordination to the resulting Rh hydride B, (3) hydride

D.M. Khramov et al. / Tetrahedron 64 (2008) 6853–6862
6857
density on the substrate may serve to weaken the bond formed
between the Rh center and the coordinated alkenyl group, facili-
tating reductive elimination and resulting in higher yields of
product. In contrast, the electron deficient nature of the latter
substrates may result in the formation of relatively strong bonds
between these two moieties, which hinders the reductive elimi-
nation process and ultimately product formation.
To explore whether the nature of the interaction formed be-
tween NHCs and Rh influence the yields of hydroboration products
obtained from functionalized phenylacetylenes, the aforemen-
3 2
tioned reactions were repeated using 6-CF and 6-NO as catalysts
(
see entries 20–25). Compared to 6-H, lower yields of product were
observed, which is likely due to the decreased electron density on
the Rh center. However, the yields of product obtained from either
6
3 2
-CF or 6-NO were similar. Thus, we conclude that the pendant
functional groups on these phenylacetylene derivatives modulate
the strength of the Rh–alkenyl bond more strongly than the NHC
ligand, thereby diminishing any noticeable effect caused by the
latter.
Figure 8. ORTEP diagram of 8-Cl. Ellipsoids are drawn at the 50% probability level.
Hydrogen atoms have been omitted for clarity. Selected bond lengths are listed in Table
2
3. The crystal structures of 8-CN and 8-NO were also obtained (not shown) and found
to be similar to 8-Cl. The crystal structure of 8-CF3 (not shown) revealed that this
complex adoped a trans geometry in the solid state.
2
.3. Synthesis and characterization of Pd complexes ligated
to electronically different NHCs
reactions mediated by (NHC) PdX -type pre-catalysts; however,
initiation rates may vary. Key bond lengths and angles for 8 are
2
2
4
5
Next, attention was directed toward exploring how NHC-based
ligands bearing different functional groups influenced Pd-catalyzed
summarized in Table 3. Complexes 8-NO and 8-CN exhibited Pd–I
and Pd–Ccarbene bond lengths that were shorter than the respective
2
4
3
Heck-type cross-coupling reactions. Using previously reported
bond lengths in 8-H and 8-Cl. Similar differences were observed in
proctocols,9 (NHC)
a
29
2
2
PdI complexes (8) bearing the same NHCs as
the series of Rh complexes reported in our previous studies,
4
6
in the aforementioned Rh complexes (i.e., 6 and 7) were prepared
which were ultimately attributed to p-backbonding interactions.
from their corresponding imidazolium salts and Pd(OAc)
2
(see
ꢁ
Fig. 7). After 2 h at 80–100 C in DMSO-d
6
, NMR scale experiments
indicated that the desired complexes formed in quantitative yields
with concomitant formation of AcOH. Furthermore, electron de-
ficient imidazoliums qualitatively reacted much faster than their
electron rich analogues, supporting the notion that acetate func-
2.4. Deducing
catalyzed by Pd–NHC complexes
s- and p-contributions in Heck reactions
With a range of Pd complexes in hand, attention turned toward
exploring their utilities in catalyzing Heck-type coupling re-
9
a
tions as a base in these reactions. For syntheses performed on
preparative scales, a 10 mol % excess of imidazolium salt was used
47
actions. In general, 1 mol % 8 was added to a DMF solution con-
taining tert-butyl-acrylate (1.4 equiv) and an aryl halide (1.0 equiv),
and then heated under nitrogen in the presence of NaOAc
4
4
to ensure complete consumption of Pd(OAc)
2
.
Ultimately, Pd
complexes 8 were obtained in excellent yields (90–96%) by pouring
their corresponding reaction mixtures into excess water upon
completion, which caused the precipitation of pale yellow solids
that were later collected by filtration. Complexes 8 were found to be
stable to ambient air and moisture and could be stored for months
without any noticeable decomposition.
ꢁ
(1.5 equiv). Preliminary studies indicated that, in our hands, 120 C
was the optimal temperature for these coupling reactions. At lower
temperatures (i.e., 100 C), very low yields of product were
obtained for all the Pd–NHC catalyst systems reported herein. At
elevated temperatures (i.e., 140 C), catalyst decomposition was
observed, as evidenced by the formation of Pd . Due to the high
temperatures employed, a series of control experiments involving
ꢁ
ꢁ
0
In addition to NMR and mass spectroscopy, Pd complexes 8 were
characterized by X-ray crystallography. With the exception of 8-
CF
where the NHC ligands were cis to each other (an ORTEP of 8-Cl is
shown in Fig. 8 as a representative example). Although 8-CF
3
, all complexes adopted pseudo-square planar geometries
Pd(OAc) (no NHC ligand) were performed in parallel to see if ill-
2
defined Pd species that may have formed over the course of the
4
4
3
,
reaction are catalytically active.
Furthermore, initial studies
which adopted a trans geometry, was different than the other
complexes prepared, it has been previously shown that such dif-
ferences do not influence ultimate product yields of coupling
revealed that all coupling reactions were complete in less than
18 h; hence, all reactions were performed for this amount of time
(see below for additional details on the kinetics of these reactions).
Product yields were determined by gas chromatography (GC) using
an internal standard (mesitylene); results are summarized in
Table 4.
I
R1
R1
Although no universal trend was observed amongst the cata-
N
N
N
N
Pd(OAc)2
DMSO
3
lysts studied, 8-CF appeared to exhibit higher activities than
2PdI2
R2
R2
1
8-NO when 4-bromobenzene or 4-bromoanisole was used as
2
8
0 - 100 °C
substrate. As described above, trifluoromethyl and nitro groups
2
8
-H (R = R = H), 95%
30
possess identical electronegativities; hence, the relative activities
8
8
8
8
-Cl (R1 = R2 = Cl), 93%
exhibited by 8-CF
tributions formed between their respective NHCs and Pd. The rel-
atively high yields of product obtained with 8-CF may be
3 2
and 8-NO may be attributed to s- and p-con-
-CF3 (R1 = H; R2 = CF ), 92%
3
-NO2 (R1 = H; R2 = NO ), 90%
3
2
-CN (R1 = R2 = CN), 96%
explained in terms of the overall donating ability of its respective
NHC being similar to benzimidazolylidene, a ligand that has been
4
8
Figure 7. Synthesis of Pd–NHC complexes 8.
reported to be highly efficient for Heck couplings. Importantly,

6858
D.M. Khramov et al. / Tetrahedron 64 (2008) 6853–6862
Table 3
Selected bond lengths (Å) and angles ( ) for Pd complexes 8
ꢁ
Bond
8-Ha
8-Cl
8-CF
3
8-CN
8-NO
2
Pd1–I1
2.6526(9)
1.993(3)
1.351(4)
1.341(5)
105.2(3)
2.6426(3)
2.003(3)
1.355(4)
1.340(4)
105.2(3)
2.5965(9)
2.006(9)
1.342(11)
1.355(14)
104.5(7)
2.6317(3)
1.998 (4)
1.341(5)
1.353(6)
105.7(3)
2.6384(7)
2.002(8)
1.338(10)
1.368(2)
104.9(8)
Pd1–C1
C1–N1/2
C2–C3
N1–C1–N2
a
Data reproduced from Ref. 3e.
these substrates produced very little product when Pd(OAc)
2
was
The active catalyst for the Heck reactions described above is
4
9
0
used without NHC ligand, even at various loadings.
While these results underscore the importance of differentiat-
- and - components in NHCs to optimize yields, the overall
believed to be a mono NHC-ligated Pd complex, formed via in situ
II
23b,52
reduction of Pd and loss of a NHC ligand.
To gain support for
ing
s
p
this hypothesis, complex 9, which contains 1,3-dimethylimidazo-
3
a,53
activities displayed by these catalysts were relatively low, with
many substrates, such as aryl chlorides (not shown), failing to react.
However, 4-iodoanisole and aryl bromides bearing activating
groups (e.g., CHO) afforded the expected products in excellent
lylidene and pyridine, a ligand known
to exhibit higher pro-
8
pensities toward dissociation, was prepared as shown in Figure 9
and studied as a pre-catalyst. As shown in Table 4 (entry 7), com-
plex 9 afforded coupled products in yields that were comparable to
5
4
(>97%) yields. As expected for substrates containing deactivating
those obtained with 8-H.
functional groups, 4-bromoanisole afforded lower yields of product
when compared to bromobenzene for all catalysts investigated.
Since the nature of the base used in Pd-mediated coupling re-
Based on the generally accepted mechanism (see Fig. 10), the
rate-limiting step of Pd-catalyzed Heck reactions is usually
0
assigned to the oxidative addition of a Pd species into an aryl
5
0
25
actions is known to often have a profound effect on reaction rates,
3
halide. Hence, it was surprising that 8-CF and 8-CN were the two
we envisioned that the use of stronger bases might facilitate re-
generation of active Pd species better than NaOAc and thus lead to
most active catalysts studied as they appeared amongst the least
likely to undergo rate-limiting oxidative addition. Furthermore, in
similar studies, Organ demonstrated that benzimidazolylidenes
bearing electron-withdrawing fluorines in their 4- and 5-positions
0
higher yields of product. Indeed, as summarized in Table 4, im-
proved yields were observed when the aforementioned coupling
51
23
reactions were performed using K
2
CO
3
as base.
resulted in the lowest yields of product.
Hence, we surmised that the observed results may be explained
by catalyst stability. To gain support for this hypothesis, a kinetic
study comparing the activity of 8-H (a Pd complex containing
a relatively electron rich NHC that should favor oxidative addition)
with 8-CN (a Pd complex containing a relatively electron deficient
NHC) over time was performed. The aforementioned catalysts were
Table 4
Yields of products obtained by coupling tert-butylacrylate with various aryl halides
using various Pd complexes as catalysts
a
X
2
9
selected due to their large difference in electronic properies. 4-
Bromoanisole and tert-butylacrylate were chosen as coupling
partners due to the relatively high yields of products obtained with
these catalysts. The reaction conditions were analogous to those
described in Table 4. As shown in Figure 11, it was apparent that
while 8-H initiated faster than 8-CN, the former lost all catalytic
activity after approximately 1.5 h. In contrast, despite relatively
slow initiation kinetics, 8-CN remained active for more than 8 h,
O
O
Pd catalyst, base
t
t
Bu
Bu
O
DMF, 120 °C, 18 h Ar
O
R
Entry
Catalyst
R:
X:
H
OMe
Br
OMe
Br
CHO
Cl
Br
Base:
NaOAc
NaOAc
K
2
CO
3
2 3
K CO
5
5
1
2
3
4
5
8-H
8-Cl
19
11
76
8
60
1
8
4
28
4
1
5
47
42
75
22
87
5
1
1
1
3
10
0
which ultimately afforded a higher yield of product. Assuming
oxidative addition is the rate-limiting step, the resting state of the
8-CF
3
0
catalyst is likely to be a mono-ligated NHC Pd complex (see above).
8-NO
8-CN
2
Hence, we propose that the enhanced stability of 8-CN is due to
b
its
rich Pd .
Collectively, these results suggested to us that for catalysts
p-withdrawing cyano groups, which serve to stabilize electron
6
Pd(OAc)
9
2
0
7
10
7
45
0
a
General reaction conditions: catalyst (1 mol %), [aryl halide]
0
¼0.33 M, [tert-
butylacrylate]
0
¼0.47 M, [base]
0
¼0.5 M, [mesitylene]
0
¼0.33 M (internal standard),
bearing electron-withdrawing groups there is a fine balance be-
ꢁ
0
DMF as solvent, 120 C, nitrogen atmosphere, 18 h. All reactions were performed in
triplicate. Reported yields were determined by GC and are ꢂ5%. Notes: 4-MeO–PhI
and 4-CHO–PhBr afforded >97% yield of product for all catalysts and bases studied.
PhCl and 4-CHO–PhCl afforded no appreciable yield of product for all catalysts and
tween stabilizing Pd intermediates and slowing down the rate of
reductive
elimination
oxidative
addition
LnPd0
bases studied.
RR1
b
RX
2
Pd(OAc) was used without any NHC ligand. Similar results were obtained when
these coupling reactions were loaded with 2, 0.1, or 0.01 mol % Pd(OAc)
2
(no NHC
ligand or precursors).
R
R
LnPd
LnPd
R1
X
I
H
H
H
H
I
N
N
N
N
Pd(OAc)2 / KI
pyridine
105 °C
Pd N
I
transmetalation
MR1
9, 98%
MX
Figure 9. Synthesis of Pd–NHC complex 9.
Figure 10. Generally accepted mechanism for Pd-catalyzed cross-coupling reactions.

D.M. Khramov et al. / Tetrahedron 64 (2008) 6853–6862
6859
1
00
and toluene were distilled from Na/benzophenone and degassed by
two freeze-pump-thaw cycles. All reagents were purchased from
commercial suppliers and were used without further purification.
1
H NMR spectra were recorded using a Varian Gemini (300 MHz or
80
60
40
20
0
400 MHz) spectrometer. Chemical shifts are reported in delta (d)
units, expressed in parts per million (ppm) downfield from tetra-
methylsilane using the residual protio solvent as an internal stan-
13
dard (CDCl
recorded using a Varian Gemini (75 MHz or 100 MHz) spectrome-
ter. Chemical shifts are reported in delta ( ) units, expressed in
parts per million (ppm) downfield from tetramethylsilane using the
solvent as an internal standard (CDCl , 77.0 ppm; DMSO-d
9.5 ppm). C NMR spectra were routinely run with broadband
3 6
, 7.24 ppm; DMSO-d , 2.49 ppm). C NMR spectra were
d
3
6
,
13
3
8-H
-CN
decoupling. IR spectra were recorded using Perkin–Elmer Spectrum
BX FTIR system. High-resolution mass spectra (HRMS) were
obtained with a VG analytical ZAB2-E or a Karatos MS9 instrument
and are reported as m/z (relative intensity). Crystallographic data
8
0
100
200
Time (min)
300
400
500
(excluding structure factors) for the structures in this paper have
been deposited with the Cambridge Crystallographic Data Centre.
Copies of the data can be obtained, free of charge, on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: þ44 (0) 1223
Figure 11. Plots of yield versus time for the Heck reaction of tert-butylacrylate
with 4-bromoanisole, as catalyzed by 8-H and 8-CN. Conditions: catalyst (1 mol %),
[
4-bromoanisole]
0
¼1.0 M, [tert-butylacrylate]
0
¼1.1 M, [K
2
CO
3
]
0
¼2.0 M, [mesityl-
3
36033 or e-mail: deposit@ccdc.cam.ac.uk).
ꢁ
ene]
0
¼1.0 M (internal standard), DMF as solvent, 120 C, nitrogen atmosphere. Yields
were determined by GC.
4.2. 1,3-Dimethyl-4-trifluoromethylimidazolium iodide
oxidative addition. Indeed, close examination of Table 4 reveals
A 30 mL vial was charged with 4-trifluoromethylimidazole
that 8-NO
-CF . These subtleties highlight the sensitivity of catalytic
activities toward electronic substitution and particularly the
2
generally afforded lower yields of product compared to
3 3
(1.0 g, 7.35 mmol), NaHCO (0.62 g, 7.35 mmol), 20 mL CH CN, 5 mL
8
3
CH I, and stir bar. The vial was then sealed and the mixture was
3
ꢁ
stirred at 60 C. After 24 h, the solvent was removed, which affor-
relative contributions of
complexes.
s
- and
p
-interactions present in NHC–Pd
ded the desired product as a 1:1 (inseparable) mixture with NaI in
1
quantitative yield. H NMR (DMSO-d ):
6
d
9.42 (s, 1H), 8.61 (s, 1H),
): 141.4, 126.5, 121.5
13
3.92 (s, 3H), 3.88 (s, 3H). C NMR (DMSO-d
6
d
19
(
d
q, JC–F¼41.3 Hz), 118.6 (q, JC–F¼267 Hz), 36.5, 35.1. F NMR (DMSO-
3
. Conclusions
In conclusion, we have synthesized and characterized a series of
ꢀ60.28. HRMS [M]þ calcd for C
6
):
d
6 9 3 2
H F N : 166.0712; found:
166.0718.
Rh and Pd complexes ligated to NHC ligands that bear different
functional groups. These complexes were explored as catalysts for
facilitating two important synthetic reactions: Rh-mediated
hydroborations and Pd-mediated Heck reactions. Particular atten-
tion was directed toward exploring how the nature of the func-
tional group appended to the NHC ligand influenced the outcomes
of the aforementioned reactions. In Rh-catalyzed hydroborations
4.3. 1,3-Dimethyl-4-trifluoromethylimidazolylidene AgI
A 30 mL pressure vessel was charged with a mixture of 1,3-di-
methyl-4-trifluoromethylimidazolium iodide/NaI (0.44 g of mate-
rial, 1.0 mmol azolium), Ag O (0.23 g, 0.55 mmol), CH Cl (15 mL),
2
2
2
and a stir bar. After sealing the vessel, the reaction mixture was
ꢁ
involving phenylacetylene, NHCs bearing
p
-withdrawing groups
stirred at 50 C for 2 h. Subsequent cooling to ambient temperature
were found to afford lower yields of products when compared to
s
-
caused solids to precipitate, which were later removed via filtra-
tion. Evaporation of the residual solvent under reduced pressure
withdrawing analogues. However, essentially no differences were
observed in hydroborations of 1-octyne under otherwise identical
conditions. Similar overall results were observed in Pd-catalyzed
Heck reactions between tert-butylacrylate and certain aryl halides.
Namely, differences in reaction yield were observed for Pd-catalysts
1
afforded 0.4 g (90% yield) of desired product as a white powder. H
1
3
NMR (DMSO-d ):
6
d 8.25 (s, 1H), 3.92 (s, 3H), 3.88 (s, 3H). C NMR
19
(DMSO-d ):
6
d
189.2, 126.3, 121.5 (m), 37.0. F NMR (DMSO-d ):
6
ꢀ59.76.
bearing NHCs with
logues bearing -withdrawing groups. Collectively, these results
support the notion that NHCs not only participate in -interactions
p-withdrawing groups as compared to ana-
s
4.4. Rh complex 6-CF
3
p
with transition metals, an often disputed argument, but such in-
teractions can influence catalytic activities. These results should
also provide useful guidelines for the future design and optimiza-
A
20 mL flask was charged with 1,3-dimethyl-4-tri-
fluoromethylimidazolylidene AgI (0.12 g, 0.30 mmol), [Rh(cod)Cl]
73 mg, 0.15 mmol), THF (10 mL), and a stir bar. The resulting
2
(
5
6
tion of metal catalysts bearing NHC ligands.
ꢁ
mixture was then stirred at 50 C for 4 h. Afterward, the reaction
mixture was cooled to ambient temperature and then filtered
4
4
. Experimental
.1. General
through a 0.2
mm PTFE filter. Removal of residual solvent under
reduced pressure afforded 0.12 g (95% yield) of desired product as
1
yellow solid. H NMR (CDCl
3
):
.10 (s, 3H), 3.27 (s, 2H), 2.39 (br, 4H),1.96 (br, 4H). C NMR (CDCl
189.6 (d, JC–Rh¼51.3 Hz), 123.9, 120.7, 118.1, 99.8 (br), 68.3 (d,
d 7.19 (s, 1H), 5.06 (s, 2H), 4.17 (s, 3H),
13
4
d
3
):
All reactions were performed under an atmosphere of nitrogen
using standard Schlenk techniques or in a nitrogen filled glove-box.
N,N-Dimethylformamide (DMF) was dried with molecular sieves
and degassed by two freeze-pump-thaw cycles. Tetrahydrofuran
JC–Rh¼12.6 Hz), 38.3, 36.2, 32.9 (d, JC–Rh¼11.2 Hz), 28.8 (d, JC–Rh¼
19
þ
10.4 Hz). F NMR (CDCl
3
):
d
ꢀ61.58. HRMS [MꢀCl] calcd for
14 19 3 2
C H F N
Rh: 375.0555; found: 375.0550. Crystals suitable for

6860
D.M. Khramov et al. / Tetrahedron 64 (2008) 6853–6862
þ
X-ray analysis were obtained by slow diffusion of hexanes vapor
into concentrated acetone solution of 6-CF ; CCDC 675951.
overlapping minor isomer), ꢀ60.34 (s, 0.8F). HRMS [M] calcd for
3
12 14 6 4 2
C H F N PdI : 685.8252; found: 685.8256. Crystals suitable for X-
ray analysis were obtained by slow diffusion of water into a con-
centrated DMSO solution of 8-CF ; CCDC 675947.
4
.5. Rh complex 7-CF
3
3
A 5 mL flask was charged with 6-CF
3
(30 mg, 73
m
mol), CDCl
3
4.9. Pd complex 8-NO
2
(
3 mL), and a stir bar. The resulting reaction mixture was then
subjected to slight pressure of CO (using a balloon). After 1 h, the
reaction was complete as determined by NMR spectroscopy. Re-
moval of residual 1,5-cyclooctadiene (and solvent) was not
After charging
imidazolium iodide (0.54 g, 2.0 mmol), Pd(OAc)
0.95 mmol), 15 mL DMSO, and a stir bar, the resulting reaction
mixture was heated to 80 C for 1 h. Subsequent cooling to ambient
temperature followed by addition of 50 mL of H
vessel caused solids to precipitate. The solids were collected by
filtration, washed with 50 mL of H O, and then dried under reduced
pressure to afford 0.58 g (90% yield) of the desired product as
a yellow powder. Although the solution structure of this complex
a
25 mL flask with 1,3-dimethyl-4-nitro-
(0.21 g,
2
ꢁ
attempted because (NHC)Rh(CO)
2
Cl type complexes are generally
unstable in the solid state. H NMR (CDCl ): 7.37 (s, 1H), 4.00 (s,
H), 3.94 (s, 3H). 13C NMR (CDCl
):
184.8 (d, JC–Rh¼68.4 Hz), 180.8
57 1
3
d
2
O to the reaction
3
3
d
(
3
d, JC–Rh¼59 Hz), 124.57 (d, C–F¼5.1 Hz), 119.4 (q, JC–Rh¼355 Hz),
2
19
þ
9.0, 37.0. F NMR (CDCl
3
):
d
ꢀ61.51. HRMS [Mꢀ2CO] calcd for
C
H
6 7
ClF N Rh: 301.9305; found: 301.9310.
3 2
1
was found to be predominantly (>95%) cis by H NMR spectros-
4
.6. Pd complex 8-H
copy, equimolar quantities of two isomers exhibiting C2v and S
2
1
symmetries were observed. H NMR (DMSO-d
6
):
d
8.78 (s, 1H), 8.77
): 169.4, 139.5,
2
PdI :
13
After charging a 25 mL flask with 1,3-dimethylimidazolium io-
(s, 1H), 4.19 (s, 3H), 3.94 (s, 3H). C NMR (DMSO-d
6
d
þ
dide (0.45 g, 2.0 mmol), Pd(OAc)
and a stir bar, the resulting reaction mixture was heated to 120 C
with stirring for 2 h. Subsequent cooling to ambient temperature
followed by the addition of 40 mL of H
caused solids to precipitate. The solids were collected by filtration,
washed with 20 mL of H O, and then dried under reduced pressure
to afford 0.5 g (95% yield) of the desired product as yellow powder.
2
(0.21 g, 0.95 mmol), 15 mL DMSO,
127.40, 127.34, 39.6, 39.4. HRMS [M] calcd for C10
H
14
N
6
O
4
ꢁ
641.8201; found: 641.8204. Crystals suitable for X-ray analysis were
obtained by slow diffusion of hexanes into a concentrated CHCl
solution of 8-NO ; CCDC 675951.
3
2
O to the reaction vessel
2
2
4.10. Pd complex 8-CN
5
8
Spectroscopic data matched the literature reports.
After charging a 25 mL flask with 1,3-dimethyl-4,5-dicyanoi-
midazolium iodide (0.56 g, 2.0 mmol), Pd(OAc) (0.21 g,
2
4
.7. Pd complex 8-Cl
0.95 mmol), 15 mL DMSO, and a stir bar, the resulting reaction
mixture was heated to 80 C for 1 h. Subsequent cooling to ambient
ꢁ
After charging a 25 mL flask with 1,3-dimethyl-4,5-dichloro-
imidazolium iodide (0.59 g, 2.0 mmol), Pd(OAc) (0.21 g,
.95 mmol), 15 mL DMSO, and a stir bar, the resulting reaction
temperature followed by addition of 50 mL of H
vessel caused solids to precipitate. The solids were collected by
filtration, washed with 50 mL of H O, and then dried under reduced
pressure to afford 0.60 g (96% yield) of the desired product as
a yellow powder. The solution structure of this complex was found
2
O to reaction
2
0
2
ꢁ
mixture was heated to 80 C for 1 h. Subsequent cooling to ambient
temperature followed by the addition of 50 mL of H O to the re-
action vessel caused solids to precipitate. The solids were collected
by filtration, washed with 20 mL H O, and then dried under re-
2
1
1
to be predominantly (>95%) cis by H NMR spectroscopy. H NMR
13
2
(DMSO-d
6
):
d
4.04 (s, 6H). C NMR (DMSO-d
6
):
d 172.5, 115.9, 107.2,
H N PdI : 652.8387; found:
þ
duced pressure to afford 0.61 g (93% yield) of the desired product as
a yellow powder. The solution structure of this complex was found
39.0. HRMS [MþH] calcd for C14
13 8 2
652.9391. Crystals suitable for X-ray analysis were obtained by slow
diffusion of diethyl ether into a saturated DMF solution of 8-CN;
CCDC 675950.
1
1
to be predominantly (>95%) cis by H NMR spectroscopy. H NMR
13
(
DMSO-d
6
):
d
3.88 (s, 6H). C NMR (DMSO-d
6
): d 162.6, 117.1, 37.5.
þ
HRMS [M] calcd for C10
H12Cl
4
N
4
PdI : 685.6946; found: 685.6946.
2
Crystals suitable for X-ray analysis were obtained by slow cooling of
4.11. Pd complex 9
saturated DMSO solution of 8-Cl; CCDC 675948.
After charging a 100 mL flask with 1,3-dimethylimidazolium
4
.8. Pd complex 8-CF
3
2
iodide (0.54 g, 2.4 mmol), Pd(OAc) (0.72 g, 3.2 mmol), KI (5 g,
3
0 mmol), 50 mL pyridine, and a stir bar, the resulting reaction
ꢁ
After charging
fluoromethylimidazolium iodide (0.58 g, 2.0 mmol), Pd(OAc)
0.21 g, 0.95 mmol), 15 mL DMSO, and a stir bar, the resulting re-
a
25 mL flask with 1,3-dimethyl-4-tri-
mixture was heated to 105 C for 4 h. Subsequent cooling to am-
bient temperature followed by removal of solvent afforded a yellow
powder, which was triturated with chloroform (3ꢄ20 mL). Com-
bined organic extracts were then passed through a short plug of
2
(
ꢁ
action mixture was heated to 80 C for 1 h. Subsequent cooling to
ambient temperature followed by addition of 50 mL of H O to the
reaction vessel caused solids to precipitate. The solids were col-
lected by filtration, washed with 25 mL of H O, and then dried
2
silica gel (CH
2 2
Cl as eluent) to obtain 1.25 g (98% yield) of the de-
1
sired product as a orange-yellow powder. H NMR (CDCl
(m, 2H), 7.72 (m,1H), 7.31 (m, 2H), 6.90 (s, 2H), 3.95 (s, 6H). C NMR
3
):
d
9.02
1
3
2
under reduced pressure to afford 0.60 g (92% yield) of the desired
product as a yellow powder. A mixture of complexes with cis- and
(DMSO-d
6
):
d
170, 153.8, 146.1, 137.6, 124.4, 123.0, 39.0. HRMS
Pd: 407.9189; found: 407.9184. Crystals
þ
[MꢀI] calcd for C10
H13IN
3
1
trans-geometries were found by H NMR spectroscopy. Likewise,
suitable for X-ray analysis were obtained by slow diffusion of
hexanes into a saturated CHCl solution of 9; CCDC 682401.
19
the F NMR spectrum revealed that the product adopted a mixture
of various geometrical isomers in an approximately 2:2:2:1 ratio.
3
As noted in the text, X-ray crystallography revealed that 8-CF
3
4.12. General procedure used for performing hydroboration
reactions
1
adopted a trans geometry in the solid state. H NMR (DMSO-d
6
):
13
d
8.26 (m, 2H), 4.00–3.81 (m, 12H). C NMR (DMSO-d ): d 173.7,
6
1
68.8, 127.2 (q, JC–F¼7.7 Hz), 126.6 (m), 122.5–121.7 (m), 119.6 (q, JC–F
¼
A Rh complex (0.03 mmol) was first weighed into a glass vial
containing a stir bar and then sealed with a 20:400 TFE/silicone
(Alltech) septum followed by a plastic open-centered cap. THF
19
2
65 Hz), 119.4 (q, JC–F¼265 Hz), 38.2, 37.3, 37.1, 36.4. F NMR
):
ꢀ59.94 (s, 3F), ꢀ60.16 (s, 3F), ꢀ60.24 (s, 2Fþ0.8F from
(
DMSO-d
6
d

D.M. Khramov et al. / Tetrahedron 64 (2008) 6853–6862
6861
(
3 mL), Et
and an internal standard such as 1,3,5-trimethoxybenzene (61 mg,
.30 mmol) or mesitylene (0.17 mL, 1.2 mmol) were then added in
3
N (0.7 mL, 5 mmol), pinacolborane (0.14 mL, 1.0 mmol),
Chem. Soc. 2002, 124, 12557; (e) Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001,
4, 18.
. Herrmann, W. A.; Mihalios, D.; Ofele, K.; Kipfor, P.; Belmedjahed, F. Chem. Ber.
992, 125, 1795.
6. Jafarpour, L.; Stevens, E. D.; Nolan, S. P. J. Organomet. Chem. 2000, 606, 2000.
. Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1, 953.
3
5
0
1
succession. After stirring at ambient temperature for 30 min, phe-
nylacetylene (0.13 mL, 1.2 mmol) or 1-octyne (0.18 mL, 1.2 mmol)
was then added. After stirring the resulting mixture for an addi-
tional 14 h at 25 C, any residual borane was quenched through the
addition of excess MeOH (0.5 mL). An aliquot was then taken from
7
8. O’Brien, C. J.; Kantchev, E. A. B.; Valente, C.; Hadei, N.; Chass, G. A.; Lough, A.;
Hopkinson, A. C.; Organ, M. G. Chem.dEur. J. 2006, 12, 4743.
ꢁ
9. (a) Herrmann, W. A.; Schwarz, J.; Gardiner, M. G. Organometallics 1999, 18,
082; (b) Voutchkova, A. M.; Feliz, M.; Clot, E.; Eisenstein, O.; Crabtree, R. H.
4
J. Am. Chem. Soc. 2007, 129, 12834; (c) Lin, I. J. B.; Vasam, C. S. Coord. Chem.
Rev. 1998, 251, 642; (d) Wang, H. M. J.; Lin, I. J. B. Organometallics 1998, 17, 972.
10. (a) Boydston, A. J.; Williams, K. A.; Bielawski, C. W. J. Am. Chem. Soc. 2005, 127,
the crude reaction mixture, diluted with CDCl
3
, and analyzed using
H NMR spectroscopy. To the best of our knowledge, the terminal
1
59
12496; (b) Khramov, D. M.; Boystron, A. J.; Bielawski, C. W. Angew. Chem., Int. Ed.
olefin products shown in Table 2, entries 17–25, have not been
previously reported. Hence, they were isolated by column chro-
matography (hexanes/ethyl acetate as eluent) and characterized.
2006, 45, 6186; (c) Boydston, A. J.; Bielawski, C. W. Dalton Trans. 2006, 4073; (d)
Boydston, A. J.; Rice, J. D.; Sanderson, M. D.; Dykhno, O. L.; Bielawski, C. W.
Organometallics 2006, 25, 6087.
11. Cotton, F. A.; Wilkinson, G. Advanced Inorganic Chemistry, 5th ed.; Wiley-
1
-p-Methoxyphenyl-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
1
Interscience: New York, NY, 1988.
yl)ethene. H NMR (CDCl
J¼9.0, 3.1 Hz, 2H), 5.99 (br, 1H), 5.94 (d, J¼2.8 Hz, 1H), 3.79 (s, 3H),
.30 (s, 12H). 13C NMR (CDCl
): 156.8, 132.5, 127.6, 126.9, 112.7,
3.5, 55.8, 26.1. HRMS [MþH ] calcd for C15 : 261.1662;
found: 261.1666.
-p-Nitrophenyl-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-
3
):
d
7.43 (dt, J¼9.0, 3.1 Hz, 2H), 6.48 (dt,
1
2. (a) Hartwig, J. F. Angew. Chem., Int. Ed. 1998, 37, 2046; (b) Wolfe, J. P.; Wagaw, S.;
Marcox, J.-F.; Buchwald, S. L. Acc. Chem. Res. 1998, 31, 805; (c) Prim, D.;
Campagne, J.-M.; Joseph, D.; Andrioletti, B. Tetrahedron 2002, 58, 2041; (d)
Altenhoff, G.; Goddard, R.; Lehmann, C. W.; Glorius, F. J. Am. Chem. Soc. 2004,
1
8
3
d
þ
H22BO
3
126, 15195.
13. Glorius, F. Top. Organomet. Chem. 2007, 21, 1.
1
14. Courchay, F. C.; Sworen, J. C.; Coronado, A.; Wagener, K. B. J. Mol. Cat. A: Chem.
2006, 254, 111.
1
ethene. H NMR (CDCl
2
calcd for C14
3
):
d
8.16 (d, J¼8.9 Hz, 2H), 7.60 (d, J¼8.9 Hz,
1
5. F u¨ rstner, A.; Ackermann, L.; Gabor, B.; Goddard, R.; Lehann, C. W.; Mynott, R.;
þ
H), 6.23 (d, J¼2.4 Hz,1H), 6.18 (br,1H),1.31 (s,12H). HRMS [MþH ]
Stelzer, F.; Thiel, O. R. Chem.dEur. J. 2001, 7, 3236.
16. Leuthaeusser, S.; Schwazr, D.; Plenio, H. Chem.dEur. J. 2007, 13, 7195.
H19NO
4
B: 276.1407; found: 276.1411.
1
7. Alcarazo, M.; Fern a´ ndez, R.; Alvarez, E.; Lassaletta, J. M. J. Organomet. Chem.
005, 690, 5979.
8. Pr a¨ sang, C.; Donnadieu, B.; Bertrand, G. J. Am. Chem. Soc. 2005, 127, 10182.
19. Herrmann, W. A.; Sch u¨ tz, J.; Frey, G. D.; Herdtweck, E. Organometallics 2006, 25,
437.
1
-p-Cyanophenyl-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-
2
1
ethene. H NMR (CDCl
3
):
H), 6.19 (d, J¼2.7 Hz, 1H), 6.13 (br, 1H), 1.30 (s, 12H). C NMR
CDCl ): 146.1, 133.8, 132.0, 127.9, 119.2, 110.4, 84.2, 24.8. HRMS
MþH ] calcd for C15
d
7.58 (d, J¼8.5 Hz, 2H), 7.55 (d, J¼8.5 Hz,
1
13
2
(
[
2
3
þ
20. For ranking of various carbenes according to their electron-donating proper-
2
H19BNO : 256.1509; found: 256.1513.
ties, see: F u¨ rstner, A.; Alcarazo, M.; Krause, H.; Lehmann, C. W. J. Am. Chem. Soc.
2007, 129, 12676.
2
1. (a) Yun, J.; Marinez, E. R.; Grubbs, R. H. Organometallics 2004, 23, 4172; (b)
4
.13. General procedure used for performing Heck coupling
Barinet, P.; Yap, G. P. A.; Richeson, D. S. J. Am. Chem. Soc. 2003, 125, 13314.
2. (a) Chianese, A. R.; Li, X.; Janzen, M. C.; Faller, J. W.; Crabtree, R. H. Organo-
metallics 2003, 22, 1663; (b) Iglesias, M.; Beetstra, D. J.; Stasch, A.; Horton, P. N.;
Hursthouse, M. B.; Coles, S. J.; Cavell, K. J.; Dervisi, A.; Fallis, I. A. Organometallics
reactions
2
2
2
A stock solution of tert-butylacrylate (0.47 M), aryl halide
2007, 26, 4800.
(
0.33 M), and mesitylene (0.33 M) (internal standard) was first
3. (a) Hadei, N.; Kantchev, E. A. B.; O’Brien, C. J.; Organ, M. G. Org. Lett. 2005, 7,
1991; (b) O’Brien, C. J.; Kantchev, E. A. B.; Chass, G. A.; Hadei, N.; Hopkinson, A.
C.; Organ, M. G.; Setiadi, D. H.; Tang, T.-H.; Fang, D.-C. Tetrahedron 2005, 61,
prepared in DMF. In a separate vial, base (1.5 mmol), catalyst
0.01 mmol), and 3 mL of the aforementioned stock solution were
(
9723.
combined under an atmosphere of nitrogen. The vial was then
sealed and placed into an oil bath at 120 C for 18 h. Afterward, an
aliquot was removed, diluted with ethyl acetate, filtered, and then
analyzed by GC.
4. For excellent reviews of cross-coupling reactions involving organoboron
compounds see: (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457; (b)
Suzuki, A. J. Organomet. Chem. 1999, 576, 147.
ꢁ
2
5. For an excellent review on Pd-catalyzed cross couplings see: Littke, A. F.; Fu, G.
C. Angew. Chem., Int. Ed. 2002, 41, 4176.
2
6. For a theoretical analysis of a NHC–Ir complex where NHC
found to be significant, see: Scott, N. M.; Dorta, R.; Stevens, E. D.; Correa, A.;
Cavallo, L.; Nolan, S. P. J. Am. Chem. Soc. 2005, 127, 3516.
p-donation was
Acknowledgements
2
7. (a) Herrmann, W. A.; K o¨ cher, C. Angew. Chem., Int. Ed. 1997, 36, 2162; (b)
Boehme, C.; Frenking, G. Organometallics 1998, 17, 5801; (c) Green, J. C.; Herbert,
B. J. J. Chem. Soc., Dalton Trans. 2005, 1214; (d) Lee, M.; Hu, C. Organometallics
2004, 23, 976; (e) Heinemann, C.; M u¨ ller, T.; Apeloig, Y.; Schwarz, H. J. Am.
Chem. Soc. 1996, 118, 2023; (f) Boehme, C.; Frenking, G. J. Am. Chem. Soc. 1996,
We are grateful to the National Science Foundation (CHE-
645563), the U.S. Army Research Office (W911NF-05-1-0430 &
W911NF-06-1-0147), the donors of the Petroleum Research Fund as
administered by the American Chemical Society (44077-G1), and
the Robert A. Welch Foundation (F-1621) for their generous fi-
nancial support.
0
118, 2039; (g) Arduengo, A. J., III; Dias, H. V. R.; Dixon, D. A.; Harlow, R. L.;
Klooster, W. T.; Koetzle, T. F. J. Am. Chem. Soc. 1994, 116, 6812.
28. (a) Tulloch, A. D. D.; Danopoulous, A. B.; Kleinhenz, S.; Light, M. E.; Hursthouse,
M. B.; Eastham, G. Organometallics 2001, 20, 2027; (b) Hu, X.; Castro-Rodriguez,
I.; Olsen, K.; Meyer, K. Organometallics 2004, 23, 755; (c) Nemcsok, D.; Wich-
mann, K.; Frenking, G. Organometallics 2004, 23, 3640; (d) Jacobsen, H.; Correa,
A.; Costabile, C.; Cavallo, L. J. Organomet. Chem. 2006, 691, 4350.
References and notes
1
. (a) Wanzlick, H. W.; Sch o¨ nherr, H. J. Angew. Chem., Int. Ed. Engl. 1968, 7, 141; (b)
29. Khramov, D. M.; Lynch, V. M.; Bielawski, C. W. Organometallics 2007, 26, 6042.
30. Group electronegativities: H, 2.1; Cl, 3.0; CN, 3.3; CF , 3.4; NO , 3.4, see: (a)
3 2
O¨ fele, K. J. Organomet. Chem. 1968, 12, P42; (c) Cardin, D. J.; Çetinkaya, B.;
Çetinkaya, E.; Lappert, M. F. J. Chem. Soc., Dalton Trans. 1973, 514; (d) Bourissou,
D.; Guerret, O.; Gabba ı¨ , F. P. Chem. Rev. 2000, 100, 39.
Wells, P. R. Prog. Phys. Org. Chem. 1968, 6, 111; (b) Anslyn, E. V.; Dougherty, D. A.
Modern Physical Organic Chemistry; University Science Books: Sausalito, CA,
2006; p 16.
2
3
. Arduengo, A. J., III; Harlow, R. L.; Kline, M. J. Am. Chem. Soc. 1991, 113, 361.
. For excellent reviews of catalytically active transition metal complexes
containing N-heterocyclic carbenes, see: (a) Kantchev, E. A. B.; O’Briend, C. J.;
Organ, M. G. Angew. Chem., Int. Ed. 2007, 46, 2768; (b) D ı´ ez-Gonz a´ lez, S.; Nolan,
S. P. Top. Organomet. Chem. 2007, 21, 47; (c) Peris, E.; Crabtree, R. H. Coord. Chem.
Rev. 2004, 248, 2239; (d) Cavell, K. J.; McGuiness, D. S. Coord. Chem. Rev. 2004,
31. Furthermore, the pK
a
of 3-trifluoromethylbenzoic acid (5.16) in a 1:1 mixture of
CH OH/H O is very similar to that of its nitro analogue (4.85), see: De Maria, P.;
3
2
Fontana, A.; Spinelli, D.; Dell’Erba, C.; Novi, M.; Petrillo, G.; Sancassan, F. J. Chem.
Soc., Perkin Trans. 2 1993, 649.
32. (a) Smith, K.; Pelter, A.; Brown, H. C. Borane Reagents; Academic: London, 1988;
(b) Smith, K.; Pelter, A. Comprehensive Organic Synthesis; Trost, B. M., Fleming, I.,
Eds.; Pergamon: Oxford, 1991; Vol. 8; p 703; (c) Tucker, C. E.; Davidson, J.;
Knochel, P. J. Org. Chem. 1992, 57, 3482.
2
48, 671; (e) Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 41, 1290; (f) Hillier, A.
C.; Grasa, G. A.; Viciu, M. S.; Lee, H. M.; Yang, C.; Nolan, S. P. J. Organomet. Chem.
002, 653, 69.
2
4
. For representative examples, see: (a) Marion, N.; Navarro, O.; Mei, J.; Stevens, E.
D.; Scott, N. M.; Nolan, S. P. J. Am. Chem. Soc. 2006, 128, 4101; (b) Navarro, O.;
Marion, N.; Oonishi, Y.; Kelly, R. A., III; Nolan, S. P. J. Org. Chem. 2006, 71, 685; (c)
Louie, J.; Gibby, J. E.; Farnworth, M. V.; Tekavec, T. N. J. Am. Chem. Soc. 2002, 124,
33. (a) Burgess, K.; Ohlmeyer, M. J. Chem. Rev. 1991, 91, 1179; (b) Beletskaya, I.;
Pelter, A. Tetrahedron 1997, 53, 4957.
34. Ohmura, T.; Yamamoto, Y.; Miyaura, N. J. Am. Chem. Soc. 2000, 122, 4990.
35. At the conclusion of the hydroboration reaction between pinacolborane and
phenylacetylene as catalyzed by 6-H (Table 2, entry 1), the mass balance was
15188; (d) Jørgensen, M.; Lee, S.; Liu, X.; Wolkowski, J. P.; Hartwig, J. F. J. Am.

6862
D.M. Khramov et al. / Tetrahedron 64 (2008) 6853–6862
determined by 1H NMR and mass spectroscopy to be as follows: 55% hydro-
boration product, 20% poly(phenylacetylene), 7% styrene, and 7% polystyrene.
The remainder of the reaction mixture was indeterminant. For the analogous
reaction with 1-octyne (entry 8), the mass balance was 27% product, 45%
are effectively catalyzed by ill-defined Pd species at elevated temperatures,
which has obfuscated any conclusions regarding how electronic differences
in NHC–Pd complexes affect their respective catalytic activities in these
reactions.
1-octyne, and 10% 1-octene; the remainder of the reaction mixture was
48. The relative electron donor abilities of 1,3-dimethyl-benzimidazolylidene
indeterminant. Pinacolborane was completely consumed in both cases.
6. Although to the best of our knowledge hydroborations using Rh–NHC com-
plexes are unknown, diborylations of styrene have been demonstrated with
Cu–NHC, Pd–NHC, Ag–NHC, Au–NHC, and Pt–NHC complexes and hydro-
borations mediated by Pt–NHC complexes have been reported. For examples of
transition metal mediated diborylations involving NHC ligands, see: (a) Lillo,
V.; Fructos, M. R.; Ram ı´ rez, J.; Braga, A. A. C.; Maseras, F.; D ı´ az-Requejo, M. M.;
P e´ rez, P. J.; Fern a´ ndez, E. Chem.dEur. J. 2007, 13, 2614; (b) Corber a´ n, R.; Ram-
ı´ rez, J.; Sana u´ , M.; Peris, E.; Fernandez, E. Chem. Commun. 2005, 3056; (c)
Corber a´ n, R.; Ram ı´ rez, J.; Poyatos, M.; Peris, E.; Fernandez, E. Tetrahedron:
Asymmetry 2006, 17, 1759; (d) Lillo, V.; Mata, J.; Ram ı´ rez, J.; Peris, E.; Fernandez,
E. Organometallics 2006, 25, 5829; For Pt–NHC hydroborations, see: Lillo, V.;
Mata, J. A.; Segarra, A. M.; Peris, E.; Fernandez, E. Chem. Commun. 2007, 2184.
(
d
¼5.04–4.99 ppm) and 1,3-dimethyl-4,5-ditrifluoromethylimidazolylidene (5.
3
06 ppm) were determined by comparing the chemical shifts of the trans-olefins
in their respective NHC–RhCl(COD) complexes; see: Baker, M. V.; Brayshaw, S.
K.; Skelton, B. W.; White, A. H. Inorg. Chim. Acta 2004, 357, 2841.
49. We acknowledge that ill-defined Pd species may form over the course of the
reported coupling reactions, especially since high temperatures were required,
and contribute to the observed catalytic activities.44 However, our in-
terpretation of the data presented is that this is not occurring to a significant
degree.
50. (a) Shekhard, S.; Hartwig, J. F. Organometallics 2007, 26, 340; (b) B o¨ hm, V. P. W.;
Herrmann, W. A. Chem.dEur. J. 2001, 7, 4191.
51. The use of other bases, including Na
2 4
HPO , did not significantly improve the
yields of these reactions.
3
7. Voutchkova, A. M.; Appelhans, L. N.; Chianese, A. R.; Crabtree, R. H. J. Am. Chem.
Soc. 2007, 127, 17624.
52. (a) Campeau, L.-C.; Thansandote, P.; Fagnou, K. Org. Lett. 2005, 7, 1857; (b) Viciu,
M. S.; Germaneau, R. F.; Navarro-Fernandez, O.; Stevens, E. D.; Nolan, S. P.
Organometallics 2002, 21, 5470.
53. Love, J. A.; Morgan, J. P.; Trnka, T. M.; Grubbs, R. H. Angew. Chem., Int. Ed. 2002,
41, 4035.
54. Under similar reaction conditions, a Pd complex containing 1,3-dimethylimi-
dazolylidene and triphenylphosphine was found to couple alkyl acrylates with
bromobenzene in nearly the same efficiencies as 8-H, see: Schneider, S. K.;
Roembke, P.; Julius, G. R.; Loschen, C.; Raubenheimer, H. G.; Frenking, G.;
Herrmann, W. A. Eur. J. Inorg. Chem. 2005, 2973.
55. Introducing a second bolus of tert-butylacrylate and 4-bromoanisole to the
reactions catalyzed by 8-H or 8-CN after 1.5 h or 8 h, respectively, did not result
in additional product formation.
3
3
8. M a¨ nnig, D.; N o¨ th, H. Angew. Chem., Int. Ed. Engl. 1985, 24, 878.
9. For detailed mechanistic studies of hydroboration reactions, see: (a) Evans, D.
A.; Fu, G. C.; Anderson, B. A. J. Am. Chem. Soc. 1992, 114, 6680; (b) Burgess, K.; van
der Donk, W. A.; Farstfer, M. B.; Ohlmeyer, M. J. J. Am. Chem. Soc. 1991, 113, 6139;
(
c) Widauer, C.; Gr u¨ tzmacher, H.; Ziegler, T. Organometallics 2000, 19, 2097; For
ab initio studies of Rh catalyzed hydroborations of alkenes, see Ref. 42.
0. For mechanistic studies of catalyzed hydrometalation of terminal alkynes, see:
4
(
(
a) Ojima, I.; Clos, N.; Donovan, R. J.; Ingallina, P. Organometallics 1990, 9, 3127;
b) Tanke, R. S.; Crabtree, R. H. J. Am. Chem. Soc. 1990, 112, 7984; (c) Jun, C.-H.;
Crabtree, R. H. J. Organomet. Chem. 1993, 447, 177; (d) Maruyama, Y.; Yamamura,
K.; Nakayama, I.; Yoshiuchi, K.; Ozawa, F. J. Am. Chem. Soc. 1998, 120, 1421.
4
1. Knorr, J. R.; Merola, J. S. Organometallics 1990, 9, 3008.
56. For example, it is known that Pd complexes bearing NHCs with bulky N-sub-
stituents (e.g., 2,6-di-iso-propylphenylimidazolylidene) are more efficient in
catalyzing cross coupling reactions than analogues with smaller NHCs; for
examples, see: (a) Grasa, G. A.; Viciu, M. S.; Huang, J.; Zhang, C.; Trudell, M. L.;
Nolan, S. P. Organometallics 2002, 21, 2866; (b) F u¨ rstner, A.; Leitner, A. Synlett
2001, 290. Efforts toward preparing and studying functionalized NHCs bearing
bulky N-substituents in catalysis are underway.
57. Upon concentration, NHC–Rh carbonyl complexes are known to dimerize with
concomitant loss of carbon monoxide, see: Sanderson, M. D.; Kamplain, J. W.;
Bielawski, C. W. J. Am. Chem. Soc. 2007, 128, 16514.
58. Herrman, W. A.; Fischer, J.; O¨ fele, K.; Artus, G. R. J. J. Organomet. Chem. 1997, 530,
4
4
2. Musaev, D. G.; Mebel, A. M.; Morokuma, K. J. Am. Chem. Soc. 1994, 116, 10693.
3. Baker, M. V.; Skelton, B. W.; White, A. H.; Williams, C. C. J. Chem. Soc., Dalton
Trans. 2001, 111.
4
4
4
4. Trace Pd is known to catalyze Heck-type coupling reactions without any ligand,
see: (a) de Vries, A. H. M.; Lunders, J. M. C. A.; Mommers, J. H. M.; Henderickx,
H. J. W.; de Vries, J. G. Org. Lett. 2003, 5, 3285; (b) Arvela, R. K.; Leadbeater, N. E.;
Sangi, M. S.; Williams, V. A.; Granados, P.; Singer, R. D. J. Org. Chem. 2005, 70, 161.
5. For an analysis of reactivity differences exhibited by cis and trans bis-NHC Pd
complexes, see: (a) McGuinness, D. S.; Green, M. J.; Cavell, K. J.; Sketon, B. W.;
White, A. H. J. Organomet. Chem. 1998, 565, 165; (b) Huynh, H. V.; Ho, J. H. H.;
Neo, T. C.; Kon, L. L. J. Organomet. Chem. 2005, 690, 3854.
259.
6. For additional evidence of
see: Hara, K.; Kanamori, Y.; Sawamura, M. Bull. Chem. Soc. Jpn. 2006, 79, 1781.
7. Efforts toward deducing - and -effects in Suzuki–Miyaura reactions catalyzed
p-backbonding interactions in NHC–Pd complexes
59. (a) Murata, B.; Kawakita, K.; Asana, T.; Watanabe, S.; Masuda, Y. Bull. Chem.
Soc. Jpn. 2002, 75, 825; (b) Takai, K.; Shinomiya, N.; Kaihara, H.; Yoshida, N.;
Moriwake, T.; Utimoto, K. Synlett 1995, 963; (c) Stewart, S. K.; Whiting, A.
J. Organomet. Chem. 1994, 482, 293; (d) Coapes, R. B.; Souza, F. E. S.;
Thomas, R. L.; Hall, J. J.; Marder, T. B. Chem. Commun. 2003, 614.
4
s
p
by 8 are underway. Preliminary experiments indicate that coupling phenyl
boronic acid to various aryl bromides, including deactivated 4-bromoanisole,