Cesium carbonate-catalyzed indium insertion into alkyl iodides and their synthetic utilities in cross-coupling reactions

Article abstract of DOI:10.1002/aoc.5110

A catalytic amount of cesium carbonate (10?mol%) was found to be capable of effectively catalyzing the insertion of indium powder into alkyl iodides. The thus-generated alkyl indium reagents could readily undergo palladium-catalyzed cross-coupling reactions with a wide variety of aryl halides, showing compatibility to a range of important functional groups.

Full text of DOI:10.1002/aoc.5110

Received: 9 May 2019
DOI: 10.1002/aoc.5110
Revised: 19 June 2019
Accepted: 21 June 2019
F U L L P A P E R
Cesium carbonate‐catalyzed indium insertion into alkyl
iodides and their synthetic utilities in cross‐coupling
reactions
Xue‐Xin Feng1,2 | Zhen Wu1,2 | Qing‐Dong Wang2 | Bing‐Zhi Chen1 | Weidong Rao3 |
Jin‐Ming Yang1,2 | Zhi‐Liang Shen1
1 School of Chemistry and Molecular
A catalytic amount of cesium carbonate (10 mol%) was found to be capable of
effectively catalyzing the insertion of indium powder into alkyl iodides. The
thus‐generated alkyl indium reagents could readily undergo palladium‐
catalyzed cross‐coupling reactions with a wide variety of aryl halides, showing
compatibility to a range of important functional groups.
Engineering, Nanjing Tech University,
Nanjing 211816, China
2 School of Pharmacy, Yancheng Teachers
University, Yancheng 224007, China
3 Jiangsu Key Laboratory of Biomass‐based
Green Fuels and Chemicals, College of
Chemical Engineering, Nanjing Forestry
University, Nanjing 210037, China
KEYWORDS
alkyl indium reagent, cesium carbonate, cross‐coupling reaction, indium, palladium
Correspondence
Jin‐Ming Yang and Zhi‐Liang Shen,
School of Chemistry and Molecular
Engineering, Nanjing Tech University.
Nanjing 211816, China.
Email: yangjm@yctu.edu.cn;
ias_zlshen@njtech.edu.cn
Funding information
Nanjing Forestry University; Yancheng
Teachers University; Nanjing Tech Uni-
versity, Grant/Award Number: 39837118
1 | INTRODUCTION
catalyst. With regard to relatively less reactive organic
halides, such as aryl halides,[5] alkenyl halides,[6] benzyl
In recent decades, organoindium reagents[1] have found
broad utilities in synthetic organic chemistry because of
their unique properties (e.g. mild reactivities, good func-
tional group tolerance, and good chemo‐ and stereo‐
selectivities) as compared with other more reactive organ-
ometallic compounds,[2] and their capabilities to partici-
pate in a wide variety of organic transformations.[1,3]
Generally, organoindium reagents could be synthesized
by means of the transmetallation of more reactive organ-
ometallic reagents with indium (III) salt[4] or via the
direct indium insertion into organohalides.[5–9] However,
the direct insertion of indium into some unactivated
organohalides normally could not take place with the sole
use of indium metal in the absence of any additive or
halides[7] and alkyl halides,[8] the insertion reactions usu-
ally should be conducted in the co‐existence of stoichio-
metric amounts of additives (such as LiX[5,6,7a,8c,d,10] or
CuX[8a–c]). Recent advancements from our lab have
shown that a catalytic amount of indium (III) chloride
or iodine was also able to catalyze the direct insertion of
metallic indium into alkyl halides.[11] In continuation of
our efforts to develop efficient methods for the generation
of organoindium reagents, herein we describe an efficient
methodology for the synthesis of alkyl indium com-
pounds through a Cs2CO3‐catalyzed[12] direct oxidative
addition of indium powder into alkyl iodides, as well as
their ensuing cross‐coupling reactions with a variety of
aryl halides. Both the insertion and the subsequent
Appl Organometal Chem. 2019;e5110.
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© 2019 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.5110

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FENG ET AL.
cross‐coupling reaction worked with good efficiency,
showing good tolerance to various functional groups.
catalyze the present indium insertion reaction. Moreover,
it should be mentioned that the reaction either could not
work in the absence of any catalyst (entry 13) or
proceeded sluggishly when relatively less reactive (2‐
bromoethyl)benzene or (2‐chloroethyl)benzene was used
in place of (2‐iodoethyl)benzene (< 5% yield).
2 | RESULTS AND DISCUSSION
Initially, a myriad of bases were tested to see their perfor-
mance in catalyzing the direct indium insertion into typ-
ical alkyl iodide of (2‐iodoethyl)benzene (1a) in THF at
60°C for 12 hr. As outlined in Table 1, it was good to find
that various bases were capable of catalyzing the inser-
tion reaction with differing catalytic activities. Of the dif-
ferent metallic carbonates screened (entries 1–6), cesium
carbonate exhibited the best catalytic activity, leading to
the desired alkyl indium reagent in 80% NMR yield (entry
4). In contrast to inorganic base, the use of organic base
as reaction catalyst led to either poor product yield (entry
7) or no visible formation of product (entries 8 and 9). In
addition, we also examined the use of some other cesium
salts as reaction catalyst (entries 10–12); however, only
reduced performances were observed when they were
used in place of cesium carbonate. The results indicated
that both cesium cation and carbonate ion were effective
for the smooth progress of the transformation, though the
reasons behind the catalytic effect are not clear thus far. It
is interesting to know that base could also be used to
With cesium carbonate being recognized as the most
efficient base catalyst for the insertion reaction, subse-
quently we investigated the substrate scope of the reac-
tion by applying the formed alkyl indium reagent to
TABLE 2 Substrate scope study by using various aryl halidesa,b
Entry
Substrate
Product
Yield (%)b
1
2
3
2a (R = Ac)
2b (R = CN)
2c (R = NO2)
3a
3b
3c
81
71
89
4
5
2d
2e
3d
3e
87
98
TABLE 1 Optimization of reaction conditionsa
Entry
Catalyst
Yield (%)b
1
Li2CO3
Na2CO3
K2CO3
Cs2CO3
Ag2CO3
NaHCO3
DMAP
DBU
54
6
7
2f (X = I)
3f
52
63
2
30
2g (X = Br)
3g
3
25
4
80 (53)c
5
45
0
8
9
2h (X = I)
2i (X = Br)
3h
3i
84
44
6
7
34
0
8
9
DBACO
CsCl
0
10
2j
3j
58
10
11
12
13
52
76
27
0
CsBr
CsOAc
–
11
12
2k
2l
3k
3l
85
70
aThe insertion step was performed at 60°C for 12 hr by using (2‐iodoethyl)
benzene (1a, 1 mmol), indium (1.5 mmol), catalyst (0.1 mmol) in THF (2 ml).
bThe yield was determined by 1H‐NMR spectroscopy by using 1,4‐
dimethoxybenzene as an internal standard.
aSee the Supporting Information for detailed reaction conditions.
cUsing 1 equiv. of indium powder.
bYield of isolated product based on aryl halides 2a–l as limiting reagent.

FENG ET AL.
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palladium‐catalyzed cross‐coupling reactions with vari-
ous aryl halides. As shown in Table 2, the thus‐generated
alkyl indium compound efficiently underwent Pd‐
catalyzed reactions with a wide variety of aryl halides,
producing the corresponding cross‐coupled products in
moderate to good yields. Aryl iodides containing nitro
group at the para, meta and ortho positions of the phenyl
ring all reacted well with alkyl metallic reagent to deliver
the expected products 3c–e with equal ease (entries 3–5).
Besides normal aryl halides, heteroaryl iodides (e.g. 2j
and 2l) were also proven to be suitable substrates for
the coupling reactions, affording the desired products 3j
and 3l in reasonable yields (entries 10 and 12). A range
of functional groups, including acetyl (2a), cyano (2b),
nitro (2c–e), ester (2f–g) and formyl (2h–j), were found
to be compatible with the mild reaction conditions, which
could potentially be derivatized at a stage where they are
required.
reactions with aryl iodide 2a, giving rise to the antici-
pated products 4b–d in good yields (entries 1–3). In the
same manner, alkyl iodides containing cyano (1e), ester
(1f) and OTBS (1g) group also participated well in the
organic transformations, providing the corresponding
products 4e–g in moderate to good yields (entries 4–6).
Aside from linear alkyl iodides, branched alkyl iodides
1h–i were also able to effectively undergo the reactions
with moderate performance, leading to the cross‐coupled
products 4h–i in acceptable yields (entries 7 and 8). How-
ever, no desired product was obtained when sterically
hindered tert‐BuI was used as substrate, which might be
due to the steric hindrance of the t‐Bu group.
3 | CONCLUSIONS
In summary, a catalytic amount of cesium carbonate
(10 mol%) was found to be capable of effectively catalyz-
ing the insertion of indium powder into alkyl iodides.
The generated alkyl indium reagents could be easily
transformed into cross‐coupled products after undergoing
palladium‐catalyzed cross‐coupling reactions with a wide
variety of aryl halides. A range of important functional
groups were tolerated, due to the mild reaction conditions
and the mildness of the formed alkyl indium compounds.
Next, a spectrum of structurally varied alkyl iodides
was surveyed as reaction substrates. As shown in
Table 3, alkyl iodides 1b–d with varying carbon chain
length were amenable to the insertion reaction as well
as the ensuing palladium‐catalyzed cross‐coupling
TABLE 3 Substrate scope study by using various alkyl iodidesa
4 | EXPERIMENTAL
4.1 | The insertion step 1
Entry
Substrate
Product
Yield (%)b
1
2
1b
1c
4b
4c
73
84
Alkyl iodide (1 mmol), indium (172.2 mg, 1.5 mmol),
cesium carbonate (32.6 mg, 0.1 mmol) and analytical
grade THF (2 ml) were added in a flask equipped with a
septum and a magnetic stir bar. The reaction mixture
was vigorously stirred at 60°C for 12 hr. Then, the upper
clear solution was carefully separated from the bottom
black precipitate by centrifuge. The remaining black pre-
cipitate was additionally stirred with THF (3 ml), and the
THF layer was carefully separated from the bottom pre-
cipitate by pipette. The combined organic layers were
concentrated under vacuum. The crude mixture was
directly used in the next step without further purification.
3
4
5
1d
1e
1f
4d
4e
4f
94
86
44
6
7
8
1g
1h
1i
4g
4h
4i
45
53
64
4.2 | The cross‐coupling step 2
To the above residue was added aryl halide (0.7 mmol),
LiCl (84.8 mg, 2 mmol), Pd (PPh3)4 (57.8 mg, 0.05 mmol)
and DMA (2 ml), and the reaction mixture was stirred at
100°C for 24 hr. Upon completion of the reaction, the reac-
tion mixture was directly purified by flash silica gel column
aSee the Supporting Information for detailed reaction conditions.
bYield of isolated product based on aryl iodide 2a as limiting reagent.

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ACKNOWLEDGEMENTS
The authors gratefully acknowledge the financial support
from Nanjing Tech University (Start‐up Grant No.
39837118), Yancheng Teachers University, and Nanjing
Forestry University.
ORCID
Zhi‐Liang Shen https://orcid.org/0000-0002-3365-9288
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SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of the
article.
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How to cite this article: Feng X‐X, Wu Z, Wang
Q‐D, et al. Cesium carbonate‐catalyzed indium
insertion into alkyl iodides and their synthetic
utilities in cross‐coupling reactions. Appl
Organometal Chem. 2019;e5110. https://doi.org/
10.1002/aoc.5110
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