Rhodium(III)-Catalyzed Selective Direct Olefination of Imidazoles

Article abstract of DOI:10.1002/adsc.201701515

Rhodium(III)-catalyzed chelation-assisted highly regio- and stereoselective direct olefination of imidazoles with olefins has been developed. A broad range of C2-substituted N-(2-pyrimidyl)imidazoles underwent smooth C5-olefination with both activated and unactivated olefins to furnish the corresponding products in good to excellent yields with high tolerance of functional groups on both coupling partners in the presence of a cationic rhodium(III) catalyst. The combination of a catalytic amount of Cu(OAc)₂ (copper(II) acetate) and O₂ (oxygen) serves as the terminal oxidant. This protocol strongly relies on the use of 2-substituted imidazoles as the substrates, and the presence of readily installable and removable pyrimidyl directing group was found to be critical for catalysis. Mechanistic studies suggest the involvement of a five-membered rhodacycle as the key intermediate in the catalytic cycle. The method can also be extended to the coupling reaction of benzimidazoles with olefins. (Figure presented.).

Full text of DOI:10.1002/adsc.201701515

Title: Rhodium(III)-Catalyzed Selective Direct Olefination of Imidazoles
Authors: Lijin Xu, Haoqiang Zhao, Jianbin Xu, Changjun Chen, Xin Xu,
Yixiao Pan, Zongyao Zhang, and Huanrong Li
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201701515
Link to VoR: http://dx.doi.org/10.1002/adsc.201701515

10.1002/adsc.201701515
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Rhodium(III)-Catalyzed Selective Direct Olefination of
Imidazoles
Haoqiang Zhao,a Jianbin Xu,a Changjun Chen,a Xin Xu,a Yixiao Pan,a Zongyao Zhang,a
Huanrong Lia and Lijin Xu*,a
a Department of Chemistry, Renmin University of China, Beijing 100872, China.
Phone: 86-10-62511528, Fax: 86-10-62516444, 20050062@ruc.edu.cn
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract: Rhodium(III)-catalyzed chelation-assisted of 2-substituted imidazoles as the substrates, and the presence
highly regio- and stereoselective direct olefination of of readily installable and removable pyrimidyl directing
imidazoles with olefins has been developed. A broad group was found to be critical for catalysis. Mechanistic
range of C2-substituted N-(2-pyrimidyl)imidazoles studies suggest the involvement of
a five-membered
underwent smooth C5-olefination with both activated and rhodacycle as the key intermediate in the catalytic cycle. The
unactivated olefins to furnish the corresponding products method can also be extended to the coupling reaction of
in good to excellent yields with high tolerance of benzimidazoles with olefins.
functional groups on both coupling partners in the
presence of
combination of
a
cationic rhodium(III) catalyst. The
catalytic amount of Cu(OAc)2
a
Keywords: Rhodium; olefination; imidazole; C-H activation;
pyrimidyl
(copper(II) acetate) and O2 (oxygen) serves as the
terminal oxidant. This protocol strongly relies on the use
Introduction
Substituted imidazoles constitute key structure units
in a broad range of biologically active natural
products and pharmaceutical compounds.[1] For
example, midazolam (A)[1i] serves as a sedative
before and during surgeries and medical procedures;
Losartan (B)[1i] and olmesartan (C)[1i] are widely used
drugs targeting hypertension; the imidazole-linked
tripeptide D[1l] is
farnesyltransferase
a
promising inhibitor of
(Figure 1). Furthermore,
imidazoles are known as versatile precursors to N-
heterocyclic carbene ligands for important catalytic
transformations, and serve as starting materials for
the preparation of useful imidazolium-based ionic
liquids.[2,3] Consequently, the efficient construction of
imidazoles has been a topic of sustained interest
during the past several decades,[4] and still attracts
much research attention today.[5] With an aim to
avoid the disadvantages associated with traditional
cyclocondensation routes to imidazole compounds
such as multistep syntheses, low reaction efficiency,
limited substrate scope and the use of sensitive
reagents, a great deal of effort has been dedicated to
the use of transition-metal catalyzed cross-coupling
reactions for the preparation of functionalized
imidazole derivatives.[6] Although much progress has
been made in this area, the necessity for prior
preparation of halogenated or metalated imidazole
starting materials greatly limited the versatility and
applicability of these approaches.
Figure 1. Some examples of imidazole-containing
pharmaceuticals and bioactive molecules.
In past decades, transition-metal catalyzed C–H
activation has undergone extensive investigation as
an efficient, atom- and step-economical strategy for
direct
functionalization
of
various
useful
heterocycles.[7] Accordingly, it is not surprising that
the development of short routes for the preparation of
functionalized imidazoles through imidazyl C-H
bonds activation/functionalization under transition-
metal catalysis has received considerable interest,[8]
and promising results in direct C-H arylation,[9]
carbonylation,[10] alkylation[11] and annulation[12] of
imidazoles have been achieved. However, studies
1
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10.1002/adsc.201701515
Advanced Synthesis & Catalysis
regarding direct olefination of imidazole C-H bonds
has been less investigated despite the potential utility
of such products.[13] The Nakao and Hiyama group
first reported the selective direct olefination of N-
selective olefination of various imidazoles and
benzoimidazoles with activated olefins and unactivat
ed olefins using a readily installable and removable
pyrimidyl group as the directing group (Scheme 1b).
This method features broad substrate scope, excellent
regio- and stereo-selectivity and high functional
group tolerance.
substituted imidazoles with alkynes using
a
Ni(0)/lewis acid catalytic system, but the use of an
excess amount of imidazoles, limited substrate scope
and employing alkynes with little functionality
decreased the attractiveness of this chemistry
(Scheme 1a).[13a] Thereafter, Ong and co-workers
demonstrated the Pd-catalyzed direct C2-olefination
of N-methyl imidazole with styrene, but only one
example was reported (Scheme 1a), and the general
utility of this chemistry has never been explored.[13b]
Results and Discussion
At the outset of our investigations, we first
attempted the coupling reaction of 2-(1H-imidazol-1-
yl)pyrimidine with nbutyl acrylate under Rh(III)
catalysis (Scheme 2a). It was expected that the
reaction should take place at the most acidic C2-
position to give butyl (E)-3-(1-(pyrimidin-2-yl)-1H-
imidazol-2-yl)acrylate as the product. However, a
variety of Rh(III) catalytic systems including those
that have proved to be effective in catalysing direct
olefination
of
structurally
similar
2-
phenylpyrimidines,[16i]
indoles[18c,18e,19i,19p]
1-(pyrimidin-2-yl)-1H-
2-(1H-pyrrol-1-
and
yl)pyrimidines,[18c,18e,19i,19p] turned out to be totally
ineffective, and only the starting materials were
recovered (For details, see supporting information).
Then the reaction of 2-(1H-imidazol-1-yl)pyrimidine
with [Cp*RhCl2]2 with NaOAc as the base in DCE at
room temperature was carried out, and only the
complex C2 was isolated, and the formation of the
expected five-membered rhodacycle C1 was not
detected (Scheme 2b). The structure of C2 was
determined by single-crystal X-ray diffraction
analysis, in which the imidazole N(3) atom
coordinates with the Rh(III) centre and both C(2)-H
and C(5)-H bonds remain intact.[21] Clearly, this
strong coordination of the imidazole N(3) atom with
the Rh(III) centre prevented the catalyst from
interacting with the imidazole C-H bonds via
coordinating with the pyrimidine, thereby resulting in
the failure of direct C-H olefination under Rh(III)
catalysis. With an aim to overcome this problem, we
reasoned that the introduction of a C2-substitutent on
2-(1H-imidazol-1-yl)pyrimidine would disfavor the
coordination of the imidazole N atom with Rh(III)
centre and facilitate the chelation-assisted direct C5-
H activation. Bearing this in mind, we then initiated
our studies by investigating the coupling reaction of
2-(2-methyl-1H-imidazol-1-yl)pyrimidine (1a) and
nbutyl acrylate (2a) in the presence of [Cp*RhCl2]2
(2.5 mol%) catalyst, and AgSbF6 (10.0 mol%)
additive at 130 C. With Cu(OAc)2 as the oxidant, the
reaction in 1,2-dichloroethane (DCE) indeed
delivered the target product 3aa in 73% isolated yield
in 2 h (Table 1, entry 1), thereby validating the
feasibility of our strategy. However, the reaction
failed to proceed when replacing 1a with either 2-(4-
methyl-1H-imidazol-1-yl)pyrimidine or 1-methyl-3-
Scheme 1. Regioselective direct olefination of imidazoles.
Recently
Rh(III)-catalyzed
direct
C-H
functionalization has emerged as a straightforward
and powerful tool for the regioselective formation of
carbon–carbon and carbon–heteroatom bonds due to
their high selectivity, broad substrate scope and
excellent functional group tolerance.[14] In this context,
direct olefination of inert aryl and alkenyl C-H bonds
with olefins under Rh(III) catalysis has attracted
much attention among the synthetic community, and
the contributions from the groups of Miura,[15]
Glorius,[16] Li[17], Loh[18] and others[19] are noteworthy.
In these reports, Cp*(pentamethylcyclopentadienyl)
ligated rhodium complexes proved to be effective
catalysts for this kind of transformation, and a variety
of directing groups containing oxygen, nitrogen and
sulfur atoms have exhibited their remarkable ability
to promote the reactivity and selectivity. In particular,
the 2-pyrimidyl and 2-pyridyl groups performed well
as readily installable and removable directing groups
in direct olefination of N-heterocycles such as
indoles,[16i,18c,18e,19i,19p]
pyrroles[18c,18e,19i,19p]
and
indolines[18d]. Inspired by these elegant studies, we
envisioned that the installation of a pyrimidyl or
pyridyl directing groups on the N atom of the
imidazole ring may facilitate direct C-H olefination
of imidazoles in the presence of a Rh(III) catalyst. In
connection with our continuing interest in the
selective olefination of (hetero)arenes,[20] herein we
demonstrate the first example of Rh(III)-catalyzed
(pyrimidine-2-yl)
imidazolium
hexafluorophosphate[22] in spite of their advantageous
structures. The promising result achieved with 1a
prompted us to examine the performance of other N-
2
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10.1002/adsc.201701515
Advanced Synthesis & Catalysis
protected 2-methyl-imidazoles (Table S1, supporting
information). However, no reaction occurred when
Me, Bn, Ac, Tos, Boc, Piv and Me2NCO was
employed.
Only
2-(2-methyl-1H-imidazol-1-
yl)pyridine (1a’) was reactive, affording the expected
product butyl (E)-3-(2-methyl-1-(pyridin-2-yl)-1H-
imidazol-5-yl) acrylate (3a’a) in 53% yield.
Obviously, N-(2-pyrimidyl) directing group proved to
be the best choice. Using the optimal N-(2-pyrimidyl)
directing group, the effect of solvent was then
explored. The reaction efficiency was maintained
when replacing DCE with PhCl, acetone and THF
(Table1, entries 2, 3 and 5), but switching to MeCN,
1,4-dioxane and alcoholic solvents led to lower yields
(Table 1, entries 4,6,8-10). Delightfully, the best
solvent was identified as dimethoxyethane (DME),
affording 3aa in 92% yield (Table 1, entry 7).
Subsequent optimization revealed that Cu(OAc)2
outperformed other commonly employed oxidants
(Table 1, entries 11-16). However the generation of
copious inorganic waste made this process less
ecofriendly and economical. Then we investigated the
combination of catalytic amount of Cu(OAc)2 with
O2 as the oxidant. It was found that the reaction
provided essentially the same yield of 3aa in the
presence of 60 mol% of Cu(OAc)2 under an
atmosphere of O2 (Table 1, entry 17). The yield of
3aa dropped to 81% when conducting the reaction at
a lower temperature (120 C) (Table 1, entry 18).
When the loading of [Cp*RhCl2]2 was reduced, the
yield decreased as well (Table 1, entry 19). The
control experiments showed that the reaction did not
take place in the absence of either [Cp*RhCl2]2,
AgSbF6 or oxidant (Table 1, entries 20-22). Thus the
optimal reaction conditions were finally determined
as follows: [Cp*RhCl2]2 (2.5 mol%), AgSbF6 (10.0
mol%) and Cu(OAc)2 (60 mol%)/O2 (1 atm) in DME
at 130 C for 2 h.
Entry
Solvent
Oxidant
Yield(%)b
1
2
3
4
5
6
7
8
DCE
PhCl
acetone
MeCN
THF
1,4-dioxane
DME
MeOH
EtOH
iPrOH
DME
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2•H2O
Ag2CO3
AgOAc
Ag2O
O2 (1.0 atm)
Tempo
Cu(OAc)2/O2
Cu(OAc)2/O2
Cu(OAc)2/O2
Cu(OAc)2/O2
Cu(OAc)2/O2
none
73
71
72
37
69
63
92
61
59
42
72
52
31
27
12
11
91
81
71
NR
NR
NR
9
10
11
12
13
14
15
16
17c
18c,d
19c,e
20c,f
21c,g
22
DME
DME
DME
DME
DME
DME
DME
DME
DME
DME
DME
a)Reaction Conditions: 1a (0.2 mmol), 2a (0.3 mmol),
[Cp*RhCl2]2 (2.5 mol%), AgSbF6 (10.0 mol%), oxidant
(0.4 mmol), solvent (2.0 mL), 130 C, 2 h, under air or O2
(1 atm). b) Isolated yield. c) Cu(OAc)2 (60 mol%) and O2 (1
atm). d) Reaction temperature 120 C. [Cp*RhCl2]2 (1.0
e)
mol%) was used. f ) No [Cp*RhCl2]2. g) No AgSbF6.
With the optimized conditions in hand, we then
investigated the scope of imidazoles with olefin 2a as
the coupling partner (Table 2). It was found that a
series of 2-alkyl substituted imidazoles (1b-1h)
worked well to give the target products (3ba-3ha) in
good to excellent yields, and this reaction does not
appear to be sensitive to steric hindrance of the alkyl
groups. When the electron-deficient 1-(pyrimidin-2-
yl)-1H-imidazole-2-carbaldehyde (1i) was employed,
the product 3ia was isolated only in 42% yield.
Converting the aldehyde group into the
corresponding acetal resulted in the formation of
product 3ja in 88% yield. These results suggest that
the reaction efficiency is sensitive to the electronic
nature of the substituent on C2-position, and the
electron-rich moiety is favored. The imidazole
substrate 1k bearing a C2 olefinic substituent proved
to be a viable coupling partner, giving rise to the
target product 3ka in 88% yield. The 2,4-
disubstituted imidazoles (1l-1p) also performed
readily under the current conditions to afford the
corresponding olefinated products (3la-3pa) in good
to excellent yields. The electronic nature of a
substituent at the 4-position of the ring affected the
outcome of the reaction, and better yields were
observed in the cases of electron-rich substituents. It
is noted that the functional groups including Br
Scheme 2. Direct olefination of 2-(1H-imidazol-1-
yl)pyrimidine.
Table 1. Optimization of reaction conditions.a
3
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10.1002/adsc.201701515
Advanced Synthesis & Catalysis
(3ma), I (3na) and NO2 (3oa) were well tolerated,
further indicating the robustness of the current
catalytic system.
thereby providing the opportunity for further
elaboration.
When
2-(2-methyl-4-phenyl-1H-
To further demonstrate the potential of our
catalytic system, the reaction was extended to the
unactivated olefins, and the results are listed in Table
4. It should be noted that in these reactions the
reaction time should be extended to 24 h. It was
found that differently substituted imidazoles (1a-
1d,1p) reacted readily with the allylamide 4a to give
the desired products (5aa-5da,5pa) in moderate to
imidazol-1-yl)pyrimidine (1q) was employed, it was
found that the olefination only took place on the aryl
ring via the imidazoyl N2 chelation assistance to give
the di-olefinated product 3qa in 35% yield. It seems
that the imidazoyl group is a more powerful directing
group in this case. Finally, the reaction of 1a and 2a
could be carried out on a gram scale to give the
desired product 3aa in 88% yield under the standard
reaction conditions, clearly demonstrating the
scalability of the current transformation (For details,
see supporting information).
good
yields.
Application
of
tert-butyl
allyl(methyl)carbamate (4b) and diethyl 2-
allylmalonate (4c) in this transformation led to the
formation of 5ab and 5ac in 46% and 51% yields,
respectively. However, vinylcyclohexane (4d) were
Table 2. Direct olefination of various imidazoles with
demonstrated to generate
a
mixture of the
2a.[a,b]
thermodynamically favourable conjugated product
together with the nonoconjugated positional isomer
(5ad), and the formation of nonoconjugated products
may result from to the migration of the C=C double
bond along the aliphatic chain.
Table 3. Direct olefination of 1a with activated olefins.[a,b]
a)Reaction Conditions: 1a (0.2 mmol), 2a (0.3 mmol),
[Cp*RhCl2]2 (2.5 mol%), AgSbF6 (10.0 mol%), Cu(OAc)2
(60 mol%) and O2 (1 atm), solvent (2.0 mL), 130 C, 2 h. b)
Isolated yield. c) 1a was olefinated in a gram scale. d) Ratio
of isomers (E/Z).
Subsequently the reactivity of various activated
olefins was evaluated in the coupling reaction with 1a.
As shown in Table 3, a wide range of commercially
available acrylates (2b-2h) underwent smooth
reaction with 1a to exclusively provide the
corresponding C5-olefinated imidazole products
(3ab-3ah) in good to excellent yields regardless of
the nature of the substituents on the oxygen atom.
Notably, under the current conditions, the acrylic
esters of tocopherol and estrone (2i,2j) exhibited
good reactivity, affording the target products
(3ai,3aj) in good yields. Similarly, the electron-
deficient diethyl vinylphosphonate (2k) and
(vinylsulfonyl)benzene (2l) successfully engaged in
the coupling reaction to give the expected products
(3ak,3al) in good yields. The synthetic protocol could
also be extended for the transformation of various
styrenes. Differently substituted styrenes (2m-2v)
proved to be suitable coupling partners to give rise to
the products (3am-3av) in moderate to good yields,
and a range of functional groups were compatible
with the reaction conditions. 2-vinylnaphthalene (2w)
was reactive, and gave the product 3aw in 61% yield.
The estrone-derived styrene 2x also proceeded
readily to deliver the product 3ax in 73% yield,
a)Reaction Conditions: 1a (0.2 mmol), 2a (0.3 mmol),
[Cp*RhCl2]2 (2.5 mol%), AgSbF6 (10.0 mol%), Cu(OAc)2
(60 mol%) and O2 (1 atm), solvent (2.0 mL), 130 C, 2 h. b)
Isolated yield.
Table 4. Direct olefination of 1a with unactivated
olefins.[a,b]
4
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10.1002/adsc.201701515
Advanced Synthesis & Catalysis
a)Reaction Conditions: 1a (0.2 mmol), 4 (0.3 mmol),
[Cp*RhCl2]2 (2.5 mol%), AgSbF6 (10.0 mol%), Cu(OAc)2
(60 mol%) and O2 (1 atm), solvent (2.0 mL), 130 C, 24 h.
b) Isolated yield. c) Ratio of isomers (styrenyl/allylic).
In order to further explore the utility of this
transformation, we next examined the direct
olefination of benzimidazoles under similar reaction
conditions. Due to the steric hindrance, a longer
reaction time of 24 h was required. As depicted in
Scheme 3, moderate to good yields were achieved in
the olefination of benzimidazole 6a with various
acrylate esters (7aa-7ac,7ag). 2-Cyclohexyl-1-
(pyrimidin-2-yl)-1H-benzo[d]imidazole (6b) was also
reactive, affording the corresponding product 7ba in
59% yield.
Scheme 4. Synthetic utility of the olefinated imidazoles.
Preliminary experiments were carried out to gain
mechanistic insight (Scheme 5). First, we
investigated the reversibility of the C-H activation
step by treating 1a with CD3CO2D under the standard
conditions in the absence or presence of olefin. As
shown in Scheme 5a, the observed H/D scrambling at
the C5-position indicated that the C(5)-H bond
undergoes reversible activation in the present Rh(I)-
based catalytic system. Further studies showed that
the thermodynamically stable five-membered
rhodacycle intermediate C3 could be easily
synthesized from the reaction of 1a with [Cp*RhCl2]2
by employing NaOAc as the base in DCE at room
temperature (Scheme 5b). Notably, complex C3
reacted stoichiometrically with 2a to give the product
3aa in a good yield in shorter time (Scheme 5c),
suggesting that C–H functionalization might be the
rate-determining step. Moreover, complex C3
exhibited almost the same catalytic activity in
reaction of 1a and 2a as [RhCp*Cl2]2 did (Scheme
5d), indicating that this five-membered complex was
indeed an active species in the catalytic cycle.
Scheme 3. Direct olefination of benzimidazoles with
acrylic esters.
These olefinated imidazole products could be
further transformed into synthetically useful
derivatives. For example, product 3aa could be
subjected to hydrolysis and hydrogenation to give the
corresponding products 8 and 9 in yields, respectively.
Furthermore, the pyrimidyl group in the coupling
products could be readily removed by treatment with
EtONa in DMSO. For example, 3aa could be
converted into the free imidazole 10 in 89% isolated
yield. Notably, alkylation of the N-3 position of the
imidazole ring with alkylating agents followed by
deprotection of the pyrimidyl group provides a useful
approach for regioselective N-alkylation of complex
imidazoles. Thus subjection of 3pa to Meerwein
reagent resulted in the formation of imidazolium
product 11, and the following cleavage of the
pyrimidyl group gave rise to the N-methylated
imidazole 12. Similar strategy has been reported by
using N-sulfamoyl protected imidazoles as the
starting materials.[5e,9i]
Scheme 5. Mechanistic studies.
5
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10.1002/adsc.201701515
Advanced Synthesis & Catalysis
400 MHz and 13C 100.6 MHz, respectively). Chemical
shifts () are given in ppm and are referenced to residual
solvent peaks, and coupling constants (J) were reported in
Hertz.
Although the exact mechanism of this coupling
reaction is still not clear, a plausible mechanism
(Scheme 6) is suggested based on previous reports[14-
19] and our results. First, coordination of the imidazole
1 to the cationic Rh(III) complex species A generated
from [RhCp*Cl2]2] and AgSbF6 would trigger ortho
C-H bond activation to give the cyclorhodium
intermediate B. The subsequent coordination of
intermediate B with the incoming olefin 2 yields
intermediate C, which is transformed into the less
hindered intermediate D by regioselective migratory
insertion of the olefin. The following β-H elimination
furnishes the desired product 3 and Rh(I) species,
which is reoxidized to Rh(III) complex A by the
oxidant to complete the catalytic cycle.
General procedure for direct olefination of imidazoles
To an oven-dried pressure tube were sequentially added
imidazole 1 (0.2 mmol), olefin 2 (0.3 mmol), [RhCp*Cl2]2
(3.10 mg, 2.5 mol%), AgSbF6 (6.87 mg, 10 mol%),
Cu(OAc)2 (21.8 mg, 0.12 mmol) and DME (2.0 mL). Then
the tube was heated and stirred vigorously at 130 C for 2
h in an oil bath under O2 (1 atm). The tube was removed
from the oil bath and cooled to room temperature. The
solvent was removed by vacuum evaporation, and the
residue was purified by column chromatography on silica
gel using a mixture of ethyl acetate and hexane to give the
pure product.
Acknowledgements
Financial support from the National Natural Science Foundation
of China (21372258) and the Fundamental Research Funds for
the Central Universities, and the Research Funds of Renmin
University of China (Program 16XNLQ04) is greatly
acknowledged.
References
[1] a) M. R. Grimmett, Comprehensive Heterocyclic
Chemistry II; A. R. Katritzky, E. F. V. Scriven, Eds.;
Pergamon: Oxford, 1996; Vol. 3, pp 77-220; b) S.
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Prod. Rep. 2009, 26, 382; e) K. Shalini, P. K. Sharma,
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Scheme 6. Plausible reaction mechanism.
Conclusion
In conclusion, we have developed a new, general
and efficient method for highly regio- and
stereoselective direct C5-olefination of imidazoles
with both activated and unactivated olefins in the
presence of a cationic Rh(III) catalyst. This method is
characterized by its high efficiency, broad range and
high functional group tolerance with regard to both
coupling partners. The key to the successful catalysis
is the appropriate choice of an imidazole substrate
and a readily installable and removable N-directing
group. Mechanistic studies were carried out and a
reaction mechanism was proposed accordingly.
Further investigation focusing on the mechanism of
the reaction and synthetic applications is underway in
our laboratory, and will be reported in due course.
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Advanced Synthesis & Catalysis
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8
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Advanced Synthesis & Catalysis
FULL PAPER
Rhodium(III)-Catalyzed Selective Direct
Olefination of Imidazoles
Adv. Synth. Catal. Year, Volume, Page – Page
Haoqiang Zhao, Jianbin Xu, Changjun Chen, Xin
Xu, Yixiao Pan, Zongyao Zhang, Huanrong Li and
Lijin Xu*
9
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