Full text of DOI:10.1016/j.tetlet.2017.11.058

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Iridium-Catalyzed Carbonyl Group-Directed Oxidative Coupling of Arenes
with Alkenes
Kumaran Elumalai, Weng Kee Leong
PII:
S0040-4039(17)31492-2
https://doi.org/10.1016/j.tetlet.2017.11.058
TETL 49501
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Tetrahedron Letters
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30 November 2017
Please cite this article as: Elumalai, K., Leong, W.K., Iridium-Catalyzed Carbonyl Group-Directed Oxidative
Coupling of Arenes with Alkenes, Tetrahedron Letters (2017), doi: https://doi.org/10.1016/j.tetlet.2017.11.058
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Iridium-Catalyzed Carbonyl Group-Directed
Oxidative Coupling of Arenes with Alkenes
Kumarane Elumalai and Weng Kee Leong
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1
Tetrahedron Letters
journal homepage: www.els evier.com
Iridium-Catalyzed Carbonyl Group-Directed Oxidative Coupling of Arenes with
Alkenes
Kumaran Elumalai , ∗ and Weng Kee Leong
aDivision of Chemistry and Biological Chemistry, Nanyang Technological University, 21 Nanyang Link, Singapore 637371.
ARTICLE INFO
ABSTRACT
Article history:
Received
The iridium complex [Cp*IrCl2]2 is a good catalyst for the directed oxidative coupling of arenes
with alkenes; a wide range of carbonyl functionalities (NHCOR, CONH2 and COR) can be
employed as the directing group.
Received in revised form
Accepted
Available online
2009 Elsevier Ltd. All rights reserved.
Keywords:
Iridium
Directed oxidative coupling
Carbonyl
Arene
Alkene
1. Introduction
salts, such as, AgBF4 and AgSbF6, may be used as additive
(entries 2 & 3), but the additive, oxidant (Cu(OAc)2) and catalyst
The oxidative coupling of arenes with alkenes to form
vinylarenes is an attractive alternative to the Mizoroki-Heck
coupling reaction with the advantage that it is atom economic and
does not require functionalized coupling partners.1 After the
initial discovery of the stoichiometric reaction between Pd(II)-
olefin complexes and arenes,2 a catalytic version involving
Pd(OAc)2 and an oxidant emerged.3 Chelation-assisted oxidative
coupling of an arene with an alkene, via orthometallation
followed by C=C bond insertion, to give an o-vinylarene is
another example of such a catalyzed oxidative coupling, which
has been demonstrated with various metal systems including
palladium,4 rhodium,5 ruthenium,6 and cobalt.7 Although there
are many studies on iridium catalyzed alkylation of arenes with
alkenes,9 there are none for the oxidative coupling of an arene
with an alkene; the closest is a direct oxidative coupling of furans
were all essential (entries 5 - 7), as is a slight excess of the
acrylate (entry 12).
Table 1. Optimization study for 1-catalysed formation of 4a
and 5a.
Entry
1
Deviation from standard conditions
none
Yield of 4+5 (%) a
86+9
80+13
80+6
49+34
15
2
AgSbF6 as additive
AgBF4 as additive
AgOAc as oxidant
no silver salt additive
no oxidant
3
with alkenes.8
We recently reported the hydroamination of
4
alkynes with aromatic amines via activation of the alkyne C≡C
bond with [Cp*IrCl2]2 (1).10 For example, the reaction of 1 with
alkyne and aniline leads to the formation of an orthometallated
aminocarbene complex via alkyne hydroamination and
subsequent ortho C-H bond activation.10a It therefore occurred to
us that it may be possible to achieve ortho C-H alkenylation of
aniline derivatives with this system.
5
6
10
7
no catalyst 1
-
8
3 mol% of 1
82+8
-
9
ACN as solvent
10
11b
12b
MeOH as solvent
reaction temperature = 30 oC
1.0 equivalent of methyl acrylate
-
The C-H activation of acetanilide, 2a, followed by oxidative
coupling to methyl acrylate was found to proceed smoothly in the
presence of 1 and additives to afford the mono- and di-
alkenylated products 4a and 5a in 86 and 9% yields, respectively
23
40+20
aIsolated yields. bIncomplete reaction.
(Table 1, entry 1). An optimization study showed that other silver
———
∗ Corresponding author. Tel.: +0-000-000-0000; fax: +0-000-000-0000; e-mail: author@university.edu

2
Tetrahedron
Changing the oxidant from Cu(OAc)2 to AgOAc increased
This suggests that the stereochemistry of alkenylation in these
cases is driven by steric factors. That halogen functional groups
were tolerated, with no dehalogenation or Heck-coupling
products observed (entries 5-8, 14). This would allow the
products to be further functionalized via other cross coupling
reactions. The reaction also proceeds with a number of other
alkenes-ethyl, t-butyl, benzyl acrylates and styrene (entries).
the yield of 5 (entry 4), while lowering the catalyst loading to 3
mol% did not affect the yield significantly (entry 8). Use of
coordinating solvents (acetonitrile or methanol) was detrimental
(entries 9 & 10) and although the reaction proceeded at ambient
temperature, it required a longer reaction time (entry 11).
A substrate scope study was carried out on a 0.2 mmol scale
with 3 mol% catalyst loading (Table 2). Acetanilides with both
electron-donating and electron-withdrawing para substituents
were tolerated, affording good yields of the mono-alkenylated
products (entries 2-6), along with ~10% yields of the di-
alkenylated products (see SI). With meta substituted acetanilides,
only mono-alkenylated products were obtained and olefination
occurred selectively para to the functional group R, irrespective
of whether it is electron-donating (R = Me) or electron-
withdrawing (R = Cl, Br) (entries 7-9). The reaction did not
proceed with unactivated alkenes (1-octene and trans-2-hexene).
With 4-acetylacetanilide, a complex mixture of products was
observed, and it occurred to us that the acetyl group could also be
directing ortho C-H bond activation. Indeed, the reaction of
acetophenone (3a) with methyl acrylate under the standard
reaction conditions gave 6a and 7a in 72% and 19% yields,
respectively (entry 15). The reaction worked well with
acetophenones carrying both electron-rich and electron-poor
substituents on the phenyl ring (entries 16-19), as well as with
acetyl naphthalenes (Scheme 1). It also worked with benzamide
(entries 20-21).
CO2Me
Table 2. Substrate scope study of 1-catalysed formation of 4a
and 5a. Yields reported are isolated yields.
O
O
O
[Cp*IrCl2]2 (5 mol%)
AgPF6 (20 mol%)
Cu(OAc)2 (2 eq)
DCE, 80 oC, 36 h
CO2CH3
CO2Me
6f
6f' (35%)
(51%)
CO2Me
O
[Cp*IrCl2]2 (5 mol%)
AgPF6 (20 mol%)
Cu(OAc)2 (2 eq)
DCE, 80 oC, 36 h
O
CO2Me
O
CO2Me
6g (67%)
Entry
1
R
DG
Product (% yield)
4a (82)
4b (80)
4c (81)
6g'
(10%)
Scheme 1
H
NHCOMe
NHCOMe
NHCOMe
NHCOMe
NHCOMe
NHCOMe
NHCOMe
NHCOMe
NHCOMe
NHCOMe
COMe
We propose a catalytic cycle, which is illustrated for
acetanilides, in Figure 1.
2
4-Me
4-OMe
4-NO2
4-Br
4-Cl
3-Br
3-Cl
3-Me
2-Cl
H
3
4
4d (64)
4e (70)
4f (66)
5
6
7
4g (75)
4h (71)
4i (89)
8
9
14
15
16
17
18
19
20
21
4n (67)
6a (72)
6b (73)
6c (79)
4-Me
4-Cl
3-OMe
2-Cl
H
COMe
COMe
COMe
6d (71)
6e (61)
8a (64)
8b (73)a
COMe
CONH2
H
CONH2
Figure 1. Proposed catalytic cycle for 1-catalyzed alkenylation of
acetanilide.
In the presence of an acetate source and a silver additive, 1 is
converted to give the active 16-electron species Cp*Ir(OAc)2,
A.4r O-coordination of the acetanilide (to form B) followed by
ortho C-H activation and the release of one molecule of acetic
acid leads to intermediate C. In the case of benzamides and
ketones, the intermediate C would be a 5- instead of a 6-
membered metallacycle. In a coordinating solvent, this step is
also presumably arrested. Coordination of the alkene (to D) and
subsequent 1,2-migratory insertion leads to intermediate E. A β-
Entry
10
R
R’
Product (% yield)
4j (90)
3-Me
3-Me
3-Me
H
CO2Et
CO2But
CO2Bz
Ph
11
4k (73)
12
4l (81)
13
4m (75)
aStyrene was used instead methyl acrylate.

3
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In summary, we have described the first instance of an
iridium-catalysed oxidative coupling of arenes with alkenes in
which the directing group is a wide range of carbonyl
functionalities (NHCOR, CONH2 or COR). It has the advantage
that halogenated derivatives are tolerated, and is competitive
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Acknowledgments
This work was supported by Nanyang Technological
University and the Ministry of Education (Research Grant No.
M4011017).
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Supplementary Material
Details of experiments and characterization data of all
products.
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4
Tetrahedron
Carbonyl directed oxidative coupling or arene
Highlights
•
with alkene
•
•
First iridium-catalysed example
Tolerant of a wide range of substituents