Rhodium(iii)-catalyzed C-H allylation of indoles with allyl alcohols: Via β-hydroxide elimination

Article abstract of DOI:10.1039/c8ob01394b

An efficient Rh(iii)-catalyzed dehydrative C-H allylation of indoles with allyl alcohols via β-hydroxide elimination under oxidant-free conditions has been developed. This method features very mild reaction conditions, excellent regioselectivity and stere

Full text of DOI:10.1039/c8ob01394b

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Takeharu Haino et al.
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Rhodium(III)-catalyzed C−H allylation of indoles with allyl alcohols
via β-hydroxide elimination†
Received 00th January 20xx,
Accepted 00th January 20xx
a
*,a,b
Xiaowei Wu, and Haitao Ji
DOI: 10.1039/x0xx00000x
An efficient Rh(III)-catalyzed dehydrative C−H allylaꢀon of indoles with allyl alcohols via β-hydroxide elimination under
oxidant-free conditions has been developed. This method features very mild reaction conditions, excellent regioselectivity
and stereoselectivity, and compatibility with various functional groups. In addition, the directing group can be removed
under mild reaction conditions, which further underscores the synthetic utility of this method.
www.rsc.org/
protein-protein interaction (PPI) inhibitors, we need to search for
new reactions to functionalize position 2 of the indole ring. Herein,
Introduction
8
we disclose the first example of an efficient Cp*Rh(III)-catalyzed
Due to the versatility of olefin transformations, the allylation of
C−H allylaꢀon of indoles with unacꢀvated allyl alcohols at room
temperature (Scheme 1, eq 4). This approach features good yields
for most substrates, excellent regio- and stereoselectivity. Further,
the reaction can easily be scaled up, and the directing group can be
removed under mild conditions.
1
(
hetero)arenes is important in organic synthesis. Arguably,
transition metal-catalyzed direct C−H allylaꢀon reacꢀons with
various allylation reagents represent a powerful strategy for atom-
2
and step-economic syntheses. In recent years, direct C−H allylaꢀon
reactions with preactivated allyl alcohol derivatives via β-oxygen
elimination have been explored by utilizing various transition
3
-5
metals, such as Rh, Ru, Co, and Mn. Among them, Cp*Rh(III)-
catalyzed allylation reactions with allyl acetates, allyl carbonates,
and allyl halides were reported by Glorius, Loh, Li, Wang, and other
Previous work
DG
H
X
Cp*RhIII
DG
DG
3
Ar
+
Ar
Ar
(1)
(2)
(3)
groups (Scheme 1, eq 1). The use of unactivated allyl alcohols as
R
R
X = OAc, OCO
2
Me,
the coupling partners was reported to result in ketones or
aldehydes under rhodium catalysis (Scheme 1, eq 2), probably due
to the preference for the β-hydride over β-hydroxide elimination.
Kanai and Matsunaga demonstrated that allyl alcohols could be
used directly for C−H allylaꢀon under Cp*Co(III) catalysis, which
OPO(OEt)
2
, etc
6
DG
H
Cp*RhIII
OH
R
Ar
+
+
R
β-hydride
elimination
O
proceeded via the β-hydroxide elimination pathway (Scheme 1, eq
7
3
). Sundararaju and co-workers compared the behavior of
R
R
OH
Cp*CoIII or RuII
-hydroxide
Cp*Co(III) for β-hydroxide elimination and Cp*Rh(III) for β-hydride
6
e
R
R
elimination in one reaction system. Recently, Kapur and Ji
reported Ru(II)-catalyzed allylation of indoles with allyl alcohols,
N
DG
β
N
elimination
DG
4
e,4g
respectively.
To the best of our knowledge, the Rh(III)-catalyzed
This work
R
R
C-H allylation with allyl alcohols via β-hydroxide elimination remains
unexplored. Therefore, the development of the reaction that allows
Cp*Rh(III) to undergo direct C-H allylation with allyl alcohols
through an uncommon β-hydroxide elimination pathway is highly
desirable. In our design and synthesis of β-catenin/T-cell factor (Tcf)
Cp*RhIII
OH
+
(4)
N
rDG
N
R
R
β
-hydroxide elimination
rDG
without [O], RT
Scheme 1. Transition metal-catalyzed C−H allylation reactions
Results and discussion
We initiated our investigation by choosing the coupling reaction
of N-substituted indole (1) with 1-phenylprop-2-en-1-ol (2a) under
Cp*Rh(III) catalysis as the model reaction to optimize the reaction
conditions. First, various directing groups were screened; we found
that the reaction did not proceed when using common directing
groups 1a-1–1a-4 (Table 1, entries 1-4). By contrast, the reaction
offered the desired product in 78% yield with excellent regio- and
stereoselectivity when using ethoxycarbamoyl as the directing
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group (entry 5). Then, we investigated the effects of solvents, halogen groups (such as fluorine, chlorine, and bromine) were
and the results showed that the yields of product were attached to the C-4, C-5 or C-6 position of indoles, the reactions all
decreased when the reaction was conducted in methanol,
dioxane, dichloromethane, and toluene (entries 6-9).
a,b
Table 2. Scope of substrates
Subsequently, the investigation of various bases indicated that
KOAc, Na CO , and CsOAc led to lower efficiency (entries 10-
2). The reaction did not afford the desired product without
the catalyst [Cp*RhCl or the base NaOAc (entry 13 and 14).
Different from rhodium catalysis (entry 5), the previously
2
3
1
2 2
]
4
g
reported reaction using [RuCl
only offered 3a with the yield of 36% at room temperature
entry 15). For the reaction conditions that either did not work
2 2
(p-cymene)] as the catalyst
(
or gave low yields of he desired product in Table 1, we only
observed unreacted starting material. No β-hydride elimination
product was observed.
a
Table 1. Optimization of Reaction Condition
b
c
No.
Solvent
DCE
Base
3a Yield (%)
E/Z ratio
d
1
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
KOAc
0
0
-
e
2
DCE
-
f
3
DCE
trace
0
-
g
4
DCE
-
h
5
DCE
83(78)
47
>25:1
h
6
MeOH
dioxane
DCM
toluene
DCE
>25:1
h
7
42
>25:1
h
8
63
>25:1
h
9
56
>25:1
h
1
0
1
2
52
-
-
-
-
-
-
h
h
1
1
DCE
Na
2
CO
3
37
DCE
CsOAc
NaOAc
-
50
S
h,i
h,j
1
3
4
DCE
0
1
DCE
trace
36
h,k
N
N
N
1
5
DCE
NaOAc
DG
DG
DG
3q, 73%
3r, 76%
3s, 82% (E/Z = 93/7)
a
Reaction conditions: 1a (0.2 mmol), 2a (0.3 mmol), catalyst (5 mol %), base
b
(
0.6 equiv.) in 2 mL solvent at room temperature, Ar atmosphere. NMR yields
using CH
2
Br
2
as an internal standard, and isolated yields in parentheses.
1 d
c
Determined by H-NMR analysis of the crude reaction mixtures. 1a-1
instead of 1a. 1a-2 instead of 1a. 1a-3 instead of 1a. 1a-4 instead of 1a. 1a
e
f
g
h
i
2 2
was used, in which ethoxycarbamoyl is the directing group. No [Cp*RhCl ] .
j
k
2 2 2 2
No NaOAc. [{RuCl (p-cymene)} ] was used instead of [Cp*RhCl ] .
a
2 2
Reaction conditions: 1 (0.2 mmol), 2a (0.3 mmol), [Cp*RhCl ] (5 mol %),
With the optimized conditions in hand, the scope of indoles was
NaOAc (0.6 equiv) in DCE (2 mL) at room temperature, Ar atmosphere, 2~6 h.
b
investigated. In general, the reaction produced the corresponding
allylation products in good yields with excellent regio- and
stereoselectivity, regardless of electron-donating and electron-
withdrawing substituents on the indole ring (Table 2). When
Unless otherwise noted, the E/Z ratios of all products are > 25:1. Isolated
c
d
yields are reported. Allyl methyl carbonate was used. AgOAc (0.6 equiv) was
o
used instead of NaOAc, 50 C.
2
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afforded the products in good yields with excellent selectivity (3b-
We then carried out a series of deuterium labeling experiments
3f). Further, a methyl or methoxyl group at the C-5 position of to probe the mechanism of the reaction. The reaction was
indoles also allowed the reaction to generate the corresponding performed with an excess amount of isotopically labeled CD OD to
3
products smoothly (3g and 3h). To investigate the influence of the determine the reversibility of the step of the C−H bond cleavage
steric hindrance at the C-3 position of indoles, the methyl and (Scheme 2a). A facile H/D scrambling was observed at the C-2 and
phenyl groups were introduced, and the desired products were C-7 positions of the indole ring, respectively (see the ESI for details).
obtained in good yields, respectively (3i and 3j).
In contrast, the H/D exchange was not observed in the absence of
the base NaOAc. Further, the reaction resulted in 25% deuteration
at the C-7 position when performed with 2a. These results indicated
that the step of C−H bond cleavage was reversible, and the reacꢀon
Next, we investigated the scope of allyl alcohols as coupling
partners under standard reaction conditions. In general, the
reaction gave the desired products in good yields with excellent
regio- and stereoselectivity when a variety of allyl alcohols were
employed as the coupling partners. Regardless of the benzene ring
of allyl alcohols bearing electron-withdrawing groups (F, Cl, Br, and
could follow
a
concerted metalation-deprotonation (CMD)
9
mechanism. Further, we conducted the reaction with deuterium-
labeled allyl alcohol 2a-D, and deuterium-labeled product 3a-D was
obtained, indicating the C-D bond of 2a-D was intact in the reaction.
The kinetic isotope effect (KIE) was measured in two parallel
reactions using 1a and deuterium-labeled 1a-D under the standard
conditions (Scheme 2b). A KIE value of 0.76 was obtained,
implicating that the step of C−H bond acꢀvaꢀon was probably not
3
CF ) or electron-donating groups (Me and MeO-), the reaction
provided the corresponding products smoothly (3k-3p). Further, the
reaction was proceeded with good efficiency when using thiophenyl
substituted allyl alcohols or naphthalenyl substituted allyl alcohols
as the coupling partners (3q and 3r). In addition, the reaction
afforded the desired products in good yields when alkyl substituted
allyl alcohols were used (3s and 3t). However, the reaction did not
1
0
involved in the rate-limiting step.
A plausible reaction pathway was proposed in Scheme 3a based
give the corresponding product when using prop-2-en-1-ol as the on the preliminary mechanistic experiments and those in the
3
,7
coupling partner. Nonetheless, the desired product 3u could be literatures. The first step is the generation of the active Rh(III)
obtained using allyl methyl carbonate. Besides, the reaction catalyst with the assistance of sodium acetate. The second step is
afforded the desired product 3v smoothly when 2-methylbut-3-en- the C-H bond activation to form the rhodacycle I. Subsequently, the
2-ol was employed as the coupling partner and silver acetate as the insertion of allyl alcohol 2 leads to intermediate II. Finally, β-
base. The use of non-terminal allyl alcohols (2n-2p) did not offer the hydroxide elimination and protonation with the aid of AcOH
products.
provides the allylation product 3 and regenerates the active
rhodium catalyst.
[Cp*RhCl2]2
a)
NaOAc
NaCl
H
N
N
3
+ H2O
Cp*Rh(OAc)2
OEt
O
N
NH
R
H
O
OEt
1a
2AcOH
2AcOH
C-H a
ctivation
hydroxide
elimination
Cp*
Rh
R
N
N
OEt
N
OH
O
Rh
N
I
O
Cp*
olefin insertion
OH
OEt
II
2
R
b)
R
R
H
H
N
OH
N
OH
Rh
Cp*
Rh
N
N
O
Cp*
O
R
OEt
III1
OEt
IV1
N
OH
hydroxide elimination
Rh
N
O
Cp*
OEt
II
OH
OH
R
R
N
H
N
H
Rh
Rh
N
OEt
III2
N
O
Cp*
O
Cp*
OEt
IV2
hydride elimination
Scheme 2. Preliminary mechanism studies
Scheme 3. Proposed mechanism
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The reason why the β-hydroxide elimination is more favored by solution was diluted with dichloromethane and washed by water.
this reaction might be determined by the stability of the transition The combined organic layers were dried with Na SO , filtered,
2
4
state structures from intermediate II to intermediates III1 and III2, concentrated and purified by column chromatography on silica gel
or by the stability of the transition state structures from (hexanes/EtOAc = 6/1 ~ 4/1, v/v) to give desired products 3.
intermediates III1 and III2 to IV1 and IV2, respectively, as shown in
Figure 3b. The key transition state structure of the β-hydroxide The gram-scale preparation of 3i:
elimination pathway might be more stable than that of the β-
hydride elimination pathway. The detailed mechanism requires
more mechanistic studies and/or DFT calculations.
III
With Cp*Rh catalyst: To a dry round bottom flask was equipped
with N-ethoxy-indole-1-carboxamides 1i in Scheme 4 (1.0 g, 4.58
mmol, 1 equiv), allylic alcohols 2a (922 mg, 6.87 mmol, 1.5 equiv),
To evaluate the efficiency and potential synthetic utility of this
methodology, a gram-scale reaction and the removal of the
directing group reaction were performed (Scheme 4a). The result
showed that the gram-scale preparation of 3i with [Cp*RhCl ] gave
[
2
Cp*RhCl ] (85.0 mg, 0.13 mmol, 0.03 equiv), NaOAc (225.5 mg,
2 2
.75 mmol, 0.6 equiv), and 40 mL 1,2-dichloroethane (DCE). The
resulting mixture was stirred at room temperature for 6 h under Ar
atmosphere. Then, the solution was diluted with dichloromethane
and washed by water. The combined organic layers were dried with
2
2
2 2
good yield. By contrast, the reaction using [RuCl (p-cymene)] was
o
used as the catalyst at 45 C only provided the product in a
moderate yield. In combination with the different results of entries
Na
2
SO
4
,
filtered, concentrated, and purified by column
chromatography on silica gel (hexanes/EtOAc = 6/1 ~ 4/1, v/v) to
5
and 15 of Table 1, and the stereoselectivities of 3t, and 3u of
give the desired product 3i (1.13 g, 74% yield).
Table 2, these results indicated that the Rh(III)-catalyzed reaction
offered higher yield, milder reaction condition and higher
4
g
II
seteroselectivity than the Ru(II)-catalyzed reaction . Further, after With Ru catalyst: To a dry round bottom flask was equipped with
many conditions were screened (described in the ESI), we found an N-ethoxy-indole-1-carboxamides 1i (1.0 g, 4.58 mmol, 1 equiv),
approach that the directing group can be removed under mild allylic alcohols 2a (922 mg, 6.87 mmol, 1.5 equiv), [RuCl
2
(p-
reaction conditions by converting the N-ethoxycarbamoyl group to cymene)] (140.3 mg, 0.23 mmol, 0.05 equiv), NaOAc (375.9 mg,
2
the Weinreb amide and then undergoing the reduction reaction.
4.58 mmol, 1 equiv) and 40 mL 1,2-dichloroethane. The resulting
mixture was stirred at 45 C for 6 h under Ar atmosphere. Then, the
o
solution was diluted with dichloromethane and washed by water.
The combined organic layers were dried with Na
2 4
SO , filtered,
concentrated, and purified by column chromatography on silica gel
(
(
hexanes/EtOAc = 6/1 ~ 4/1, v/v) to give the desired product 3i
597.0 mg, 39% yield).
Removal of the directing group:
To a solution of 3i (0.52 g, 1.55 mmol, 1 equiv) in dry DMF (20 mL)
was added NaH (74.6 mg, 60%, dispersion in mineral oil, 1.2 equiv)
o
portionwise at 0 C. The resulting mixture was stirred for 30 min at
room temperature, and then MeI (441.0 mg, 2 equiv) was added
into the solution. The reaction was stirred for 6 h at room
temperature. Then, the reaction was quenched with saturated
Scheme 4. Gram-scale reaction and the removal of the
directing group
NH
4
Cl solution. The solution was diluted with EtOAc and washed by
SO , filtered,
brine. The combined organic layers were dried over Na
2
4
concentrated, and purified by column chromatography on silica gel
Conclusions
(hexanes/EtOAc = 15/1 ~ 10/1, v/v) to give the desired product 3ia
(
498.0 mg, 92% yield).
In this study, we have reported the first example of an efficient
Rh(III)-catalyzed C−H allylaꢀon of indoles by uꢀlizing unacꢀvated To a solution of 3ia (50.0 mg, 0.14 mmol, 1 equiv) in anhydrous THF
allyl alcohols, which favors an interesting β-hydroxide elimination (5 mL) was added LiAlH (27.2 mg, 5 equiv) portionwise at room
4
over β-hydride elimination. For most substrates, the reaction can temperature. The resulting mixture was stirred for 30 min, and then
o
afford allylated products in good yields. In addition, this method the reaction was heated to 60 C for 12 h under Ar atmosphere. The
features very mild reaction conditions, excellent regio- and reaction was quenched with saturated NH Cl solution. The solution
4
stereoselectivity, and compatibility with various functional groups.
was diluted with EtOAc and washed by brine. The combined organic
layers were dried over Na SO , filtered, concentrated and purified
by column chromatography on silica gel (hexanes/EtOAc = 15/1 ~
0/1, v/v) to give the product 4a (21.0 mg, 59% yield).
2
4
Experimental
1
General procedure for the synthesis of compound 3
2
-cinnamyl-N-ethoxy-1H-indole-1-carboxamide (3a). 3a was
1
obtained as colorless oil in 78% yield, 50 mg. H NMR (500 MHz,
CDCl ) δ 8.32 (s, 1H), 7.73 – 7.70 (m, 1H), 7.54 – 7.48 (m, 1H), 7.38 –
.34 (m, 2H), 7.32 – 7.28 (m, 2H), 7.25 – 7.16 (m, 3H), 6.51 (d, J =
5.9 Hz, 1H), 6.46 (d, J = 0.8 Hz, 1H), 6.39 (dt, J = 15.9, 6.5 Hz, 1H),
.09 (q, J = 7.0 Hz, 2H), 3.88 (d, J = 6.5 Hz, 2H), 1.31 (t, J = 7.0 Hz, 3H)
To a dry tube was equipped with N-ethoxy-indole-1-carboxamides 1
3
(
[
0.2 mmol, 1 equiv), allylic alcohols 2 (0.3 mmol, 1.5 equiv),
Cp*RhCl (0.01 mmol, 0.05 equiv), NaOAc (0.12 mmol, 0.6 equiv)
7
1
4
2 2
]
and 2 mL 1,2-dichloroethane. The resulting mixture was stirred at
room temperature for 2~6 h under Ar atmosphere. Then, the
4
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1
3
ppm. C NMR (126 MHz, CDCl ) δ 152.6, 139.0, 137.1, 135.9, 132.6, 12.1 Hz), 132.9, 128.7, 127.7, 126.4, 125.4 (d, J = 1.1 Hz), 121.2 (d, J
3
1
29.3, 128.7, 127.6, 126.5, 126.4, 123.3, 122.5, 120.7, 112.5, 107.1, = 9.8 Hz), 110.8 (d, J = 24.0 Hz), 106.9, 100.2 (d, J = 28.4 Hz), 73.0,
−
19
72.9, 32.0, 13.6 ppm. HRMS (ESI) m/z: calculated for C20
H
19
N
2
O
2
[M 32.0, 13.6 ppm. F NMR (471 MHz, CDCl
3
) δ -118.38 ppm. HRMS
−
−
−
−
H] : 319.1452, found: 319.1453.
(ESI) m/z: calculated for C20
37.1359.
H18FN
2
O
2
[M − H] : 337.1358, found:
3
2
-cinnamyl-N-ethoxy-5-fluoro-1H-indole-1-carboxamide (3b). 3b
1
was obtained as colorless oil in 74% yield, 50 mg. H NMR (500 MHz,
CDCl
) δ 8.29 (s, 1H), 7.66 (dd, J = 9.0, 4.3 Hz, 1H), 7.38 – 7.34 (m, 3g was obtained as colorless oil in 71% yield, 48 mg. H NMR (500
H), 7.33 – 7.28 (m, 2H), 7.25 – 7.21 (m, 1H), 7.15 (dd, J = 8.8, 2.5 Hz, MHz, CDCl )) δ 8.28 (s, 1H), 7.59 (d, J = 8.4 Hz, 1H), 7.40 – 7.34 (m,
2-cinnamyl-N-ethoxy-5-methyl-1H-indole-1-carboxamide (3g).
1
3
2
3
1
H), 6.95 (td, J = 9.1, 2.6 Hz, 1H), 6.51 (d, J = 15.9 Hz, 1H), 6.42 (d, J 2H), 7.32 – 7.27 (m, 3H), 7.24 – 7.19 (m, 1H), 7.04 (dd, J = 8.5, 1.3 Hz,
=
3
0.7 Hz, 1H), 6.37 (dt, J = 15.9, 6.5 Hz, 1H), 4.08 (q, J = 7.0 Hz, 2H), 1H), 6.50 (d, J = 15.9 Hz, 1H), 6.43 – 6.34 (m, 2H), 4.07 (q, J = 7.0 Hz,
13
.86 (d, J = 6.4 Hz, 2H), 1.31 (t, J = 7.0 Hz, 3H) ppm. C NMR (126 2H), 3.86 (d, J = 6.4 Hz, 2H), 2.42 (s, 3H), 1.31 (t, J = 7.0 Hz, 3H) ppm.
13
MHz, CDCl
3
) δ 159.1 (d, J = 238.6 Hz), 152.5, 140.5, 136.9, 133.0,
3
C NMR (126 MHz, CDCl ) δ 152.8, 139.2, 137.2, 134.1, 132.5, 131.9,
1
32.5, 130.0 (d, J = 10.1 Hz), 128.7, 127.8, 126.4, 126.2, 113.6 (d, J = 129.6, 128.7, 127.6, 126.7, 126.3, 124.7, 120.6, 112.3, 106.9, 72.9,
−
9
.3 Hz), 111.2 (d, J = 25.5 Hz), 107.1 (d, J = 4.0 Hz), 106.0 (d, J = 23.7 32.1, 21.3, 13.6 ppm. HRMS (ESI) m/z: calculated for C21
H
21
N
2
O
2
[M
19
−
Hz), 73.0, 32.1, 13.6 ppm. F NMR (471 MHz, CDCl
3
) δ -121.40 ppm. − H] : 333.1609, found: 333.1601.
F [M − H] : 337.1358,
−
−
HRMS (ESI) m/z: calculated for C20
found: 337.1363.
H
18
N
2
O
2
2-cinnamyl-N-ethoxy-5-methoxy-1H-indole-1-carboxamide (3h).
1
3
h was obtained as colorless oil in 78% yield, 55 mg. H NMR (500
5
3
-chloro-2-cinnamyl-N-ethoxy-1H-indole-1-carboxamide (3c). 3c MHz, CDCl ) δ 8.26 (s, 1H), 7.62 (d, J = 9.0 Hz, 1H), 7.39 – 7.33 (m,
1
was obtained as colorless oil in 77% yield, 55 mg. H NMR (500 MHz, 2H), 7.33 – 7.27 (m, 2H), 7.24 – 7.17 (m, 1H), 6.96 (d, J = 2.5 Hz, 1H),
CDCl ) δ 8.29 (s, 1H), 7.64 (d, J = 8.8 Hz, 1H), 7.46 (d, J = 1.9 Hz, 1H), 6.85 (dd, J = 9.0, 2.5 Hz, 1H), 6.50 (d, J = 15.9 Hz, 1H), 6.44 – 6.35 (m,
3
7
.37 – 7.33 (m, 2H), 7.33 – 7.28 (m, 2H), 7.25 – 7.21 (m, 1H), 7.18 2H), 4.08 (q, J = 7.0 Hz, 2H), 3.86 (d, J = 6.4 Hz, 2H), 3.83 (s, 3H), 1.31
1
3
(dd, J = 8.8, 2.1 Hz, 1H), 6.50 (d, J = 15.9 Hz, 1H), 6.40 (d, J = 0.8 Hz, (t, J = 7.0 Hz, 3H) ppm. C NMR (126 MHz, CDCl ) δ 155.8, 152.8,
3
1
H), 6.39 – 6.33 (m, 1H), 4.08 (q, J = 7.0 Hz, 2H), 3.86 (d, J = 6.5 Hz, 139.7, 137.1, 132.6, 130.6, 130.2, 128.7, 127.6, 126.6, 126.3, 113.5,
1
3
2H), 1.30 (t, J = 7.0 Hz, 3H) ppm. C NMR (126 MHz, CDCl ) δ 152.3, 112.3, 107.2, 103.1, 72.9, 55.8, 32.2, 13.7 ppm. HRMS (ESI) m/z:
3
−
−
1
40.2, 136.9, 134.4, 133.0, 130.4, 128.8, 128.1, 127.8, 126.4, 126.1, calculated for C H N O [M − H] : 349.1558, found: 349.1560.
21
21
2
3
123.5, 120.1, 113.7, 106.6, 73.0, 32.0, 13.6 ppm. HRMS (ESI) m/z:
−
−
calculated for C20
18
H N
2
O
2
Cl [M − H] : 353.1062, found: 353.1066.
2-cinnamyl-N-ethoxy-3-methyl-1H-indole-1-carboxamide (3i). 3i
was obtained as colorless oil in 77% yield, 52 mg. H NMR (500 MHz,
1
5
-bromo-2-cinnamyl-N-ethoxy-1H-indole-1-carboxamide (3d). CDCl
d was obtained as colorless oil in 82% yield, 66 mg. H NMR (500 7.18 (m, 8H), 6.40 – 6.37 (m, 2H), 4.05 (q, J = 7.0 Hz, 2H), 3.87 (d, J =
3
) δ 8.34 (s, 1H), 7.78 – 7.75 (m, 1H), 7.53 – 7.48 (m, 1H), 7.33 –
1
3
13
MHz, CDCl
3
) δ 8.42 (s, 1H), 7.60 (d, J = 1.9 Hz, 1H), 7.56 (d, J = 8.8 Hz, 4.0 Hz, 2H), 2.27 (s, 3H), 1.28 (t, J = 7.0 Hz, 3H) ppm. C NMR (126
) δ 152.7, 137.0, 135.3, 132.8, 131.7, 130.3, 128.6, 127.5,
.48 (d, J = 15.9 Hz, 1H), 6.39 – 6.31 (m, 2H), 4.05 (q, J = 7.0 Hz, 2H), 127.1, 126.3, 123.6, 122.1, 118.8, 114.5, 112.7, 72.8, 29.0, 13.6, 8.8
1
6
3
H), 7.36 – 7.33 (m, 2H), 7.32 – 7.27 (m, 3H), 7.25 – 7.20 (m, 1H), MHz, CDCl
3
.82 (d, J = 6.5 Hz, 2H), 1.29 (t, J = 7.0 Hz, 3H) ppm. C NMR (126 ppm. HRMS (ESI) m/z: calculated for C H N O [M − H]−:
13
−
21 21 2 2
3
MHz, CDCl ) δ 152.2, 140.1, 136.9, 134.8, 133.0, 130.9, 128.8, 127.8, 333.1609, found: 333.1612.
1
26.4, 126.1, 126.0, 123.2, 115.7, 114.1, 106.4, 73.1, 31.9, 13.6 ppm.
−
−
HRMS (ESI) m/z: calculated for C20
found: 397.0546.
H
18
N
2
O
2
Br [M − H] : 397.0557,
2-cinnamyl-N-ethoxy-3-phenyl-1H-indole-1-carboxamide (3j). 3j
1
was obtained as colorless oil in 80% yield, 64 mg. H NMR (500 MHz,
CDCl ) δ 8.51 (s, 1H), 7.78 (dt, J = 8.4, 0.8 Hz, 1H), 7.56 – 7.54 (m,
3
4
-chloro-2-cinnamyl-N-ethoxy-1H-indole-1-carboxamide (3e). 3e 1H), 7.49 – 7.46 (m, 4H), 7.41 – 7.34 (m, 1H), 7.31 – 7.24 (m, 5H),
was obtained as colorless oil in 79% yield, 56 mg. 1H NMR (500 MHz, 7.23 – 7.17 (m, 2H), 6.41 – 6.37 (m, 2H), 4.03 (q, J = 7.0 Hz, 2H), 3.91
1
3
3
CDCl ) δ 8.53 (s, 1H), 7.57 (d, J = 8.1 Hz, 1H), 7.38 – 7.33 (m, 2H), (d, J = 4.2 Hz, 2H), 1.24 (t, J = 7.0 Hz, 3H) ppm. C NMR (126 MHz,
7
1
6
.30 (t, J = 7.6 Hz, 2H), 7.27 – 7.21 (m, 1H), 7.16 (dd, J = 7.7, 0.7 Hz, CDCl ) δ 152.3, 137.0, 135.6, 133.6, 133.6, 132.2, 129.9, 129.1,
3
H), 7.12 (t, J = 7.9 Hz, 1H), 6.55 (s, 1H), 6.50 (d, J = 15.9 Hz, 1H), 128.8, 128.7, 127.8, 127.6, 127.4, 126.3, 124.0, 122.5, 121.2, 119.9,
.36 (dt, J = 15.9, 6.5 Hz, 1H), 4.05 (q, J = 7.0 Hz, 2H), 3.82 (d, J = 6.5 112.5, 72.9, 29.4, 13.5 ppm. HRMS (ESI) m/z: calculated for
13
+
+
Hz, 2H), 1.29 (t, J = 7.0 Hz, 3H) ppm. C NMR (126 MHz, CDCl
3
) δ
52.1, 139.6, 136.9, 136.6, 133.0, 128.7, 127.9, 127.7, 126.4, 125.9,
25.9, 123.9, 122.1, 111.0, 105.0, 73.0, 31.9, 13.6 ppm. HRMS (ESI)
C
26
H
24
N
2
O
2
Na [M + Na] : 419.1735, found: 419.1727.
1
1
(E)-N-ethoxy-2-(3-(4-fluorophenyl)allyl)-1H-indole-1-
−
−
m/z: calculated for C20
H
18
N
2
O
2
Cl [M − H] : 353.1062, found: carboxamide (3k). The product was obtained as colorless oil in 70%
1
353.1064.
yield, 48 mg. H NMR (500 MHz, CDCl ) δ 8.30 (s, 1H), 7.71 (d, J = 8.2
3
Hz, 1H), 7.54 – 7.48 (m, 1H), 7.38 – 7.29 (m, 2H), 7.25 – 7.15 (m, 2H),
2
-cinnamyl-N-ethoxy-6-fluoro-1H-indole-1-carboxamide (3f). 3f 7.03 – 6.94 (m, 2H), 6.48 – 6.43 (m, 2H), 6.31 (dt, J = 15.8, 6.5 Hz,
1
was obtained as colorless oil in 68% yield, 46 mg. H NMR (500 MHz, 1H), 4.09 (q, J = 7.0 Hz, 2H), 3.87 (d, J = 6.5 Hz, 2H), 1.32 (t, J = 7.0
1
3
CDCl ) δ 8.32 (s, 1H), 7.47 (dd, J = 10.2, 2.3 Hz, 1H), 7.40 (dd, J = 8.6, Hz, 3H) ppm. C NMR (126 MHz, CDCl
3
) δ 162.4 (d, J = 246.6 Hz),
.4 Hz, 1H), 7.37 – 7.33 (m, 2H), 7.33 – 7.28 (m, 2H), 7.25 – 7.19 (m, 152.6, 139.0, 135.8, 133.3 (d, J = 3.3 Hz), 131.4, 129.3, 127.8 (d, J =
H), 6.97 – 6.93 (m, 1H), 6.50 (d, J = 15.9 Hz, 1H), 6.42 (d, J = 0.8 Hz, 7.9 Hz), 126.3, 126.3, 123.4, 122.5, 120.7, 115.6 (d, J = 21.5 Hz),
3
5
1
1
=
1
9
3
H), 6.37 (dt, J = 15.9, 6.4 Hz, 1H), 4.08 (q, J = 7.0 Hz, 2H), 3.84 (d, J 112.4, 107.1, 73.0, 31.9, 13.7 ppm. F NMR (471 MHz, CDCl ) δ -
1
3
−
−
6.4 Hz, 2H), 1.31 (t, J = 7.0 Hz, 3H) ppm. C NMR (126 MHz, CDCl3) 114.69 ppm. HRMS (ESI) m/z: calculated for C H N O F [M − H] :
20
18 2 2
δ 160.3 (d, J = 239.5 Hz), 152.4, 139.0, 138.9, 136.9, 136.1 (d, J = 337.1358, found: 337.1357.
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Organic & Biomolecular Chemistry
Page 6 of 7
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DOI: 10.1039/C8OB01394B
ARTICLE
Journal Name
(
E)-2-(3-(4-chlorophenyl)allyl)-N-ethoxy-1H-indole-1-
142.2, 138.8, 135.9, 129.3, 127.5, 126.2, 125.8, 125.5, 124.1, 123.4,
carboxamide (3l). The product was obtained as colorless oil in 78% 122.5, 120.7, 112.4, 107.1, 73.0, 31.7, 13.6 ppm. HRMS (ESI) m/z:
1
−
−
yield, 56 mg. H NMR (500 MHz, CDCl ) δ 8.31 (s, 1H), 7.71 – 7.68 (m, calculated for C H N O S [M − H] : 325.1016, found: 325.1013.
3
18 17
2
2
1H), 7.53 – 7.48 (m, 1H), 7.29 – 7.15 (m, 6H), 6.47 – 6.43 (m, 2H),
6
.36 (dt, J = 15.9, 6.4 Hz, 1H), 4.09 (q, J = 7.0 Hz, 2H), 3.86 (d, J = 6.3
(E)-N-ethoxy-2-(3-(naphthalen-2-yl)allyl)-1H-indole-1-
13
Hz, 2H), 1.32 (t, J = 7.0 Hz, 3H) ppm. C NMR (126 MHz, CDCl
3
) δ carboxamide (3r). The product was obtained as colorless oil in 76%
1
152.6, 138.9, 135.8, 135.7, 133.2, 131.3, 129.3, 128.8, 127.5, 127.3, yield, 57 mg. H NMR (500 MHz, CDCl ) δ 8.33 (s, 1H), 7.80 – 7.67 (m,
3
1
23.4, 122.5, 120.7, 112.4, 107.1, 72.9, 31.9, 13.7 ppm. HRMS (ESI) 5H), 7.59 (dd, J = 8.6, 1.7 Hz, 1H), 7.55 – 7.51 (m, 1H), 7.48 – 7.40 (m,
−
−
m/z: calculated for C20
H
18
N
2
O
2
Cl [M − H] : 353.1062, found: 2H), 7.26 – 7.16 (m, 2H), 6.67 (d, J = 15.9 Hz, 1H), 6.57 – 6.47 (m,
2H), 4.08 (q, J = 7.0 Hz, 2H), 3.94 (d, J = 6.4 Hz, 2H), 1.29 (t, J = 7.0
353.1061.
13
Hz, 3H) ppm. C NMR (126 MHz, CDCl
133.7, 133.1, 132.7, 129.3, 128.3, 128.1, 127.8, 127.0, 126.4, 126.2,
carboxamide (3m). The product was obtained as colorless oil in 75% 125.9, 123.6, 123.4, 122.5, 120.7, 112.5, 107.1, 73.0, 32.1, 13.6 ppm.
yield, 60 mg. H NMR (500 MHz, CDCl
Hz, 1H), 7.51 (d, J = 7.5 Hz, 1H), 7.44 – 7.37 (m, 2H), 7.26 – 7.16 (m, found: 369.1611.
3
) δ 152.6, 139.0, 135.9, 134.6,
(
E)-2-(3-(4-bromophenyl)allyl)-N-ethoxy-1H-indole-1-
1
−
−
3
) δ 8.27 (s, 1H), 7.70 (d, J = 8.2 HRMS (ESI) m/z: calculated for C H N O [M − H] : 369.1620,
2
4
22
2
2
4
H), 6.47 – 6.34 (m, 3H), 4.09 (q, J = 7.0 Hz, 2H), 3.87 (d, J = 5.8 Hz,
1
3
2H), 1.32 (t, J = 7.0 Hz, 3H) ppm. C NMR (126 MHz, CDCl
3
) δ 152.6,
(E)-N-ethoxy-2-(pent-2-en-1-yl)-1H-indole-1-carboxamide (3s). A
1
38.9, 136.1, 135.7, 131.8, 131.4, 129.3, 127.9, 127.5, 123.4, 122.5, mixture of stereoisomers (E/Z = 93:7) was obtained as colorless oil
1
121.3, 120.8, 112.4, 107.1, 73.0, 32.0, 13.7 ppm. HRMS (ESI) m/z: in 82% yield, 45 mg. Spectral data for the major isomer (E): H NMR
−
−
calculated for C20
18
H N
2
O
2
Br [M − H] : 397.0557, found: 397.0562.
3
(500 MHz, CDCl ) δ 8.37 (s, 1H), 7.81 – 7.76 (m, 1H), 7.51 – 7.47 (m,
1
H), 7.24 – 7.15 (m, 2H), 6.39 (d, J = 0.8 Hz, 1H), 5.65 – 5.62 (m, 2H),
(
E)-N-ethoxy-2-(3-(p-tolyl)allyl)-1H-indole-1-carboxamide (3n). 4.14 (q, J = 7.0 Hz, 2H), 3.68 – 3.60 (m, 2H), 2.11 – 2.03 (m, 2H), 1.36
1
13
The product was obtained as colorless oil in 71% yield, 48 mg. H (d, J = 7.0 Hz, 3H), 1.00 (t, J = 7.5 Hz, 3H) ppm. C NMR (126 MHz,
NMR (400 MHz, CDCl )) δ 8.31 (s, 1H), 7.73 (d, J = 8.3 Hz, 1H), 7.55 – CDCl ) δ 152.7, 139.2, 136.2, 135.7, 129.3, 125.7, 123.3, 122.4,
.46 (m, 1H), 7.27 – 7.16 (m, 5H), 7.13 – 7.08 (m, 2H), 6.50 – 6.44 120.5, 112.9, 107.0, 72.9, 31.7, 25.7, 13.8, 13.7 ppm. HRMS (ESI)
3
3
7
+
+
(
(
(
m, 2H), 6.34 (dt, J = 15.9, 6.4 Hz, 1H), 4.09 (q, J = 7.0 Hz, 2H), 3.86 m/z: calculated for C16
H
21
N
2
O
2
[M + H] : 273.1603, found:
1
3
d, J = 6.4 Hz, 2H), 2.33 (s, 3H), 1.31 (t, J = 7.0 Hz, 3H) ppm. C NMR 273.1600.
126 MHz, CDCl ) δ 152.6, 139.1, 137.4, 136.0, 134.3, 132.6, 129.4,
29.3, 126.3, 125.5, 123.3, 122.4, 120.7, 112.6, 107.1, 72.9, 32.0,
1.3, 13.7 ppm. HRMS (ESI) m/z: calculated for C H N O [M − H]−: mixture of stereoisomers (E/Z = 92:8) was obtained as colorless oil
3
1
2
3
(E)-N-ethoxy-2-(hex-2-en-1-yl)-1H-indole-1-carboxamide (3t). A
−
21
21
2
2
1
33.1603, found: 333.1608.
in 75% yield, 43 mg. Spectral data for the major isomer (E): H NMR
500 MHz, CDCl ) δ 8.43 (s, 1H), 7.79 – 7.76 (m, 1H), 7.52 – 7.46 (m,
1H), 7.25 – 7.13 (m, 2H), 6.38 (d, J = 0.8 Hz, 1H), 5.68 – 5.53 (m, 2H),
carboxamide (3o). The product was obtained as colorless oil in 74% 4.13 (q, J = 7.0 Hz, 2H), 3.66 – 3.63 (m, 2H), 2.05 – 2.00 (m, 2H), 1.41
(
3
(
E)-N-ethoxy-2-(3-(4-methoxyphenyl)allyl)-1H-indole-1-
1
13
yield, 52 mg. H NMR (500 MHz, CDCl ) δ 8.37 (s, 1H), 7.74 – 7.70 (m, – 1.34 (m, 5H), 0.89 (t, J = 7.4 Hz, 3H) ppm. C NMR (126 MHz,
3
1
6
1
H), 7.54 – 7.45 (m, 1H), 7.33 – 7.26 (m, 2H), 7.25 – 7.15 (m, 2H), CDCl
.86 – 6.80 (m, 2H), 6.47 – 6.41 (m, 2H), 6.24 (dt, J = 15.8, 6.5 Hz, 120.3, 112.8, 106.8, 72.7, 34.6, 31.6, 22.4, 13.7, 13.6 ppm. HRMS
3
) δ 152.5, 139.0, 136.0, 133.9, 129.1, 126.7, 123.1, 122.2,
+
+
22 2 2
H), 4.08 (q, J = 7.0 Hz, 2H), 3.84 (d, J = 6.5 Hz, 2H), 3.79 (s, 3H), 1.31 (ESI) m/z: calculated for C17H N O [M + H] : 287.1760, found:
1
3
(
t, J = 7.0 Hz, 3H) ppm. C NMR (126 MHz, CDCl ) δ 159.3, 152.6, 287.1756.
3
139.1, 136.0, 132.1, 129.9, 129.3, 127.5, 124.3, 123.3, 122.4, 120.6,
1
14.1, 112.6, 107.0, 72.9, 55.4, 31.9, 13.6 ppm. HRMS (ESI) m/z:
2-allyl-N-ethoxy-1H-indole-1-carboxamide (3u). The product was
obtained as colorless oil in 71% yield, 35 mg. H NMR (500 MHz,
−
−
1
calculated for C21
21
H N
2
O
3
[M − H] : 349.1558, found: 349.1561.
CDCl
7.23 - 7.14 (m, 2H), 6.40 (d, J = 0.7 Hz, 1H), 6.10 - 6.01 (m, 1H), 5.21
carboxamide (3p). The product was obtained as colorless oil in 72% - 5.10 (m, 2H), 4.13 (q, J = 7.0 Hz, 2H), 3.74 - 3.69 (m, 2H), 1.36 (t, J =
3
) δ 8.36 (s, 1H), 7.72 (d, J = 8.2 Hz, 1H), 7.49 (d, J = 7.8 Hz, 1H),
(
E)-N-ethoxy-2-(3-(4-(trifluoromethyl)phenyl)allyl)-1H-indole-1-
1
13
yield, 56 mg. H NMR (500 MHz, CDCl
.2, 0.8 Hz, 1H), 7.56 – 7.50 (m, 3H), 7.45 – 7.42 (m, 2H), 7.25 – 7.16 135.3, 129.3, 123.3, 122.4, 120.6, 117.5, 112.7, 107.1, 72.9, 32.8,
3
3
) δ 8.29 (s, 1H), 7.69 (dd, J = 7.0 Hz, 3H) ppm. C NMR (126 MHz, CDCl ) δ 152.6, 138.5, 136.0,
8
(
−
−
m, 2H), 6.55 – 6.44 (m, 3H), 4.10 (q, J = 7.0 Hz, 2H), 3.91 (d, J = 4.8 13.7 ppm. HRMS (ESI) m/z: calculated for C14
H
N
2
O
2
[M − H] :
15
13
Hz, 2H), 1.33 (t, J = 7.0 Hz, 3H) ppm. C NMR (126 MHz, CDCl
3
) δ 243.1139, found: 243.1133.
52.6, 140.7, 138.8, 135.7, 131.2, 129.5, 129.3, 126.5, 125.7 (q, JC-F
3.8 Hz), 123.5, 122.6, 120.8, 112.4, 107.2, 73.0, 32.0, 13.7 ppm.
1
=
N-ethoxy-2-(3-methylbut-2-en-1-yl)-1H-indole-1-carboxamide
3
) δ -62.49 ppm. HRMS (ESI) m/z: calculated (3v). The product was obtained as colorless oil in 40% yield, 22 mg.
1
9
F NMR (471 MHz, CDCl
+
+
1
for C21
H F
20 3
N
2
O
2
[M + H] : 389.1477, found: 389.1467.
3
H NMR (500 MHz, CDCl ) δ 8.23 (s, 1H), 7.73 – 7.65 (m, 1H), 7.45 –
7
.36 (m, 1H), 7.17 – 7.00 (m, 2H), 6.30 (d, J = 0.9 Hz, 1H), 5.30 – 5.22
(
E)-N-ethoxy-2-(3-(thiophen-2-yl)allyl)-1H-indole-1-carboxamide (m, 1H), 4.08 (q, J = 7.0 Hz, 2H), 3.60 – 3.57 (m, 2H), 1.78 – 1.61 (m,
1
3
(
3q). The product was obtained as colorless oil in 73% yield, 48 mg. 6H), 1.30 (t, J = 7.0 Hz, 3H) ppm. C NMR (126 MHz, CDCl
3
) δ 152.9,
H NMR (500 MHz, CDCl ) δ 8.33 (s, 1H), 7.72 – 7.68 (m, 1H), 7.54 – 140.3, 136.1, 135.4, 129.4, 123.2, 122.4, 120.6, 120.5, 112.8, 106.4,
1
3
7
(
.48 (m, 1H), 7.24 – 7.15 (m, 2H), 7.12 (d, J = 5.1 Hz, 1H), 6.96 – 6.88 72.9, 27.8, 25.9, 18.1, 13.7 ppm. HRMS (ESI) m/z: calculated for
+
+
m, 2H), 6.64 – 6.58 (m, 1H), 6.45 (d, J = 0.8 Hz, 1H), 6.21 (dt, J =
C
16
H
21
N
2
O
2
[M + H] : 273.1603, found: 273.1601.
1
5.7, 6.6 Hz, 1H), 4.09 (q, J = 7.0 Hz, 2H), 3.85 (d, J = 6.6 Hz, 2H),
1
3
1.31 (t, J = 7.0 Hz, 3H) ppm. C NMR (126 MHz, CDCl ) δ 152.5,
3
6
| J. Name., 2012, 00, 1-3
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Page 7 of 7
Or gP al en ai sc e& d Bo i on mo to al ed cj uu ls at r mC ha re gmi ni ss try
View Article Online
DOI: 10.1039/C8OB01394B
Journal Name
ARTICLE
2
-cinnamyl-N-ethoxy-N,3-dimethyl-1H-indole-1-carboxamide
4
For Ru(II)-catalyzed C-H allylation, see: (a) S. Oi, Y. Tanaka
and Y. Inoue, Organometallics 2006, 25, 4773; (b) M. Kim, S.
Sharma, N. K. Mishra, S. Han, J. Park, M. Kim, Y. Shin, J. H.
(
3ia). The product was obtained as colorless oil in 92% yield, 498 mg.
H NMR (500 MHz, CDCl ) δ 7.53 – 7.46 (m, 1H), 7.38 – 7.34 (m, 1H),
.31 – 7.26 (m, 3H), 7.26 – 7.16 (m, 4H), 6.44 (d, J = 15.8 Hz, 1H),
.25 (dt, J = 15.8, 6.5 Hz, 1H), 3.96 – 3.70 (m, 4H), 3.19 (s, 3H), 2.29
1
3
Kwak, S. H. Han and I. S. Kim, Chem. Commun., 2014, 50,
1303; (c) R. Manikandan, P. Madasamy and M.
7
6
(
1
1
1
1
3
Jeganmohan, Chem. - Eur. J., 2015, 21, 13934; (d) R.
Manikandan and M. Jeganmohan, Org. Biomol. Chem., 2016,
s, 3H), 1.12 (t, J = 7.1 Hz, 3H) ppm. C NMR (126 MHz, CDCl
3
) δ
53.9, 137.3, 135.4, 134.1, 131.5, 130.0, 128.6, 127.4, 127.1, 126.2,
23.0, 121.3, 118.7, 113.2, 112.0, 69.7, 37.6, 28.6, 13.7, 8.8 ppm.
1
4, 7691; (e) G. S. Kumar and M. Kapur, Org. Lett., 2016, 18
112; (f) Y. Q. Xia and L. Dong, Org. Lett., 2017, 19, 2258; (g)
,
1
X. Wu, and H. Ji, Org. Lett., 2018, 20, 2224.
+
+
HRMS (ESI) m/z: calculated for C H N O [M + H] : 349.1916,
2
2
25
2
2
found: 349.1909.
5
For Cp*Co(III) or Mn(I)-catalyzed C-H allylation, see: (a) D.-G.
Yu, T. Gensch, F. de Azambuja, S. Vasquez-Cespedes and F.
Glorius, J. Am. Chem. Soc., 2014, 136, 17722; (b) T. Gensch,
S. Vasquez-Cespedes, D.-G. Yu and F. Glorius, Org. Lett.,
2
-cinnamyl-3-methyl-1H-indole (4a). The product was obtained
1
as colorless oil in 59% yield, 21 mg. H NMR (500 MHz, CDCl
3
) δ 7.75
2
015, 17, 3714; (c) M. Moselage, J. Sauermann, J. Koeller, W.
(s, 1H), 7.55 – 7.48 (m, 1H), 7.38 – 7.33 (m, 2H), 7.33 – 7.27 (m, 2H),
Liu, D. Gelman and L. Ackermann, Synlett 2015, 26, 1596; (d)
Y. Suzuki, B. Sun, K. Sakata, T. Yoshino, S. Matsunaga and M.
Kanai, Angew. Chem., Int. Ed., 2015, 54, 9944; (e) Y. Bunno,
N. Murakami, Y. Suzuki, M. Kanai, T. Yoshino and S.
Matsunaga, Org. Lett., 2016, 18, 2216; (f) M. R. Sk, S. S. Bera,
and M. S. Maji, Org. Lett., 2018, 20, 134; (g) W. Liu, S. C.
Richter, Y. Zhang and L. Ackermann, Angew. Chem., Int. Ed.,
7
6
3
1
2
2
.27 – 7.19 (m, 2H), 7.17 – 7.06 (m, 2H), 6.51 (d, J = 15.8 Hz, 1H),
.33 (dt, J = 15.8, 6.6 Hz, 1H), 3.65 (dd, J = 6.6, 1.2 Hz, 2H), 2.28 (s,
1
3
H) ppm. C NMR (126 MHz, CDCl
3
) δ 137.1, 135.5, 132.2, 132.1,
29.5, 128.8, 127.6, 126.7, 126.3, 121.4, 119.2, 118.4, 110.5, 107.7,
+
+
9.9, 8.6 ppm. HRMS (ESI) m/z: calculated for C18
48.1439, found: 248.1430.
H18N [M + H] :
2
016, 55, 7747; (h) T. H. Meyer, W. Liu, M. Feldt, A. Wuttke,
R.A. Mata and L. Ackermann, Chem. Eur. J., 2017, 23, 5443;
i) Q. Lu, F. J. R. Klauck and F. Glorius, Chem. Sci., 2017,
379.
Conflicts of interest
(
3
8,
The authors declare no competing financial interest.
6
(a) Z. Shi, M. Boultadakis-Arapinis and F. Glorius, Chem.
Commun., 2013, 49, 6489; (b) L. Huang, Q. Wang, J. Qi, X.
Wu, K. Huang and H. Jiang, Chem. Sci., 2013, 4, 2665; (c) S.
H. Han, M. Choi, T. Jeong, S. Sharma, N. K. Mishra, J. Park, J.
S. Oh, W. J. Kim, J. S. Lee and I. S. Kim, J. Org. Chem., 2015,
80, 11092; (d) R. Manoharan and M. Jeganmohan, Chem.
Commun., 2015, 51, 2929; (e) D. Kalsi, R. A. Laskar, N. Barsu,
Acknowledgements
This work was supported by the Susan G. Komen Career
Catalyst Research Grant CCR16380693. The H. Lee Moffitt
Cancer Center & Research Institute is a NCI-designated
Comprehensive Cancer Center, supported under NIH grant
P30-CA76292.
J. R. Premkumar and B. Sundararaju, Org. Lett., 2016, 18
4
,
198; (f) J. Xia, Z. Huang, X. Zhou, X. Yang, F. Wang and X. Li,
Org. Lett., 2018, 20, 740; (g) Y. Wang, Y. Chen, Y. Yang and B.
Zhou, Org. Chem. Front., 2018, DOI: 10.1039/c8qo00265g.
(a) Y. Suzuki, B. Sun, K. Sakata, T. Yoshino, S. Matsunaga and
M. Kanai, Angew. Chem., Int. Ed., 2015, 54, 9944; (b) Y.
Bunno, N. Murakami, Y. Suzuki, M. Kanai, T. Yoshino and S.
Matsunaga, Org. Lett., 2016, 18, 2216.
Z. Huang, M. Zhang, S. D. Burton, L. N. Katsakhyan and H. Ji,
ACS Chem. Biol., 2014, 9, 193.
(a) S. I. Gorelsky, D. Lapointe and K. Fagnou, J. Am. Chem.
Soc., 2008, 130, 10848; (b) W. Ma, R. Mei, G. Tenti and L.
Ackermann, Chem. - Eur. J., 2014, 20, 15248.
7
References
1
(a) J. L. Farmer, H. N. Hunter and M. G. Organ, J. Am. Chem.
Soc., 2012, 134, 17470; (b) G. Ni, Q.-J. Zhang, Z.-F. Zheng, R.-
Y. Chen and D.-Q. Yu, J. Nat. Prod., 2009, 72, 966; (c) B. M.
Trost, O. R. Thiel and H.-C. Tsui, J. Am. Chem. Soc., 2002,
8
9
1
24, 11616.
For a recent review on C-H allylation, see: N. K. Mishra, S.
Sharma, J. Park, S. Han and I. S. Kim, ACS Catal., 2017,
821.
For Cp*Rh(III)-catalyzed C-H allylation, see: (a) H. Wang, N.
Schröder and F. Glorius, Angew. Chem., Int. Ed., 2013, 52
2
3
1
0
E. M. Simmons and J. F. Hartwig, Angew. Chem., Int. Ed.,
2
7
,
012, 51, 3066.
2
,
5
1
386; (b) C. Feng, D. Feng and T. -P. Loh, Org. Lett., 2013,
, 3670; (c) C. Feng, D. Feng and T.-P. Loh, Chem.
5
Commun., 2015, 51, 3425; (d) S.-S. Zhang, J.-Q. Wu, Y.-X.
Lao, X.-G. Liu, Y. Liu, W.-X. Lv, D.-H. Tan, Y.-F. Zeng and H.
Wang, Org. Lett., 2014, 16, 6412; (e) S. Yu and X. Li, Org.
Lett., 2014, 16, 1200; (f) J. Park, N. K. Mishra, S. Sharma, S.
Han, Y. Shin, T. Jeong, J. S. Oh, J. H. Kwak, Y. H. Jung and I. S.
Kim, J. Org. Chem., 2015, 80, 1818; (g) J. Q. Wu, Z. P. Qiu, S.
S. Zhang, J. G. Liu, Y. X. Lao, L. Q. Gu, Z. S. Huang, J. Li and H.
Wang, Chem. Commun., 2015, 51, 77; (h) S. Debbarma, S. S.
Bera and M. S. Maji, J. Org. Chem., 2016, 81, 11716; (i) H.
Dai, C. Yu, Z. Wang, H. Yan and C. Lu, Org. Lett., 2016, 18
410; (j) S.-T. Mei, N.-J. Wang, Q. Ouyang and Y. Wei, Chem.
Commun., 2015, 51, 2980; (k) S.-S. Zhang, J.-Q. Wu, X. Liu
,
3
and H. Wang, ACS Catal., 2015,
X. Li, Org. Lett., 2016, 18, 4392.
5, 210; (l) Z. Qi, L. Kong and
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