Iodine mediated/Bronsted acid-catalyzed dimerization of vinylarenes: A tandem reaction through Ritter trapping to produce N-(4-iodo-1,3-diarylbutyl) acetamides

Article abstract of DOI:10.1039/c2ob25142f

In the presence of p-toluenesulfonic acid and iodine, styrene derivatives undergo head-to-tail dimerization followed by trapping with nitriles to yield the corresponding Ritter-type products.

Full text of DOI:10.1039/c2ob25142f

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Iodine mediated/Brønsted acid-catalyzed dimerization of vinylarenes: a
tandem reaction through Ritter trapping to produce N-(4-iodo-1,3-
diarylbutyl) acetamides†
Jing-Mei Huang,*a Zhi-Jun Ye,a Dong-Song Chena and Hong Zhub
Received 18th January 2012, Accepted 15th March 2012
DOI: 10.1039/c2ob25142f
In the presence of p-toluenesulfonic acid and iodine, styrene
derivatives undergo head-to-tail dimerization followed by
trapping with nitriles to yield the corresponding Ritter-type
products.
The development of sustainable processes is one of the main
targets in modern chemistry.1 Particularly, construction of
complex structures from simple starting materials in a tandem
process through an efficient catalytic transformation is a power-
ful tool for saving energy and resources.2 Catalytic dimerization
of aryl alkenes is one of the current interesting and useful reac-
tions to construct a new C–C bond,3 and in consequence of our
interest in the development of new sustainable process in organic
synthesis,4 we report a method to build up a new series of com-
pounds N-(4-iodo-1,3-diarylbutyl)acetamides through iodine
mediated and p-toluenesulfonic acid promoted head-to-tail
dimerization of vinylarenes.
Fig. 1 The ORTEP drawing of compound 3a: N-((1R,3S)-4-iodo-1,3-
diphenylbutyl)acetamide).5
Table 1 Optimization of the reaction conditions for the dimerization
reaction of styrenea
Recently, when we investigated the Yb(OTf)3 catalyzed reac-
tion of styrene with I2 in MeCN (1 mL, commercial reagent
grade), a new product N-(4-iodo-1,3-diphenylbutyl)acetamide
3a, in which carbon skeleton was resulted from the head-to-tail
dimerization of styrene was obtained in a yield of 55%. The ratio
of two diastereoisomers was 1 : 0.8 and the structure had been
determined by IR, NMR, HRMS spectroscopic data and X-ray
diffraction.6 The ORTEP drawing is shown in Fig. 1. The inter-
esting structure and the high efficient domino process prompted
us to further optimize the current reaction conditions. Hence, a
study of reaction conditions with variation of acid and tempera-
ture is summarized in Table 1. Lewis acids ZnCl2 and SnCl2
gave slightly lower yields (49% and 48% respectively, Table 1,
entries 3 and 4). It was found that Brønsted acid also worked on
this transformation. p-Toluenesulfonic acid (PTSA) showed the
Entry
Catalyst
Temperature (°C)
Yieldb (%)
1
2
3
4
5
6
7
8
—
0 to rt
0 to rt
0 to rt
0 to rt
0 to rt
0 to rt
0 to rt
rt
0c
Yb(OTf)3
ZnCl2
SnCl2
CH3COOH
HCl
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
55 (1 : 0.8)
49 (1 : 0.8)
48 (1 : 0.9)
44 (1 : 0.8)
48 (1 : 0.8)
68 (1 : 0.7)
50 (1 : 0.7)
59 (1 : 0.7)
17 (1 : 0.7)
68 (1 : 0.7)
68 (1 : 0.7)
44 (1 : 0.7)
9
0
10d
11e
12f
13g
0 to rt
0 to rt
0 to rt
0 to rt
aSchool of Chemistry and Chemical Engineering, South China
University of Technology, Guangzhou, Guangdong510640, P.R. China.
E-mail: chehjm@scut.edu.cn; Fax: (+86) 20-87110622; Tel: +86 020
8711 0695
bExperiment and Practice Training Center, GuangDong Food and Drug
Vocational College, Guangzhou, Guangdong510520, P.R. China
†Electronic supplementary information (ESI) available: Experimental
procedures, characterization data and copies of 1H and 13C NMR spectra
for all new compounds. CCDC 838337. For ESI and crystallographic
data in CIF or other electronic format see DOI: 10.1039/c2ob25142f
a Conditions: 1 mmol styrene, 1 mmol iodine, 0.1 mmol catalyst,
solvent: 1 mL acetonitrile. b Isolated yield; the ratio of the two
diastereoisomers determined by 1H NMR was given in parenthesis. c SM
was recovered. d 0.05 mmol PTSA. e 0.125 mmol PTSA. f Anhydrous
MeCN + 0.6 mmol H2O. g 1 mL DCM, 2 mmol acetonitrile.
3610 | Org. Biomol. Chem., 2012, 10, 3610–3612
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Table 2 Dimerization of vinylarenes catalysed by PTSAa
Table 2 (Contd.)
Entry R1, R2
Product
3
Yieldb (%)
Entry R1, R2
Product
3
Yieldb (%)
11c
R1 = 2-Naphtyl
3k 38
(1 : 0.8)
1
R1 = Ph
3a 68
(1 : 0.7)
R2 = CH3
R2 = CH3
2
R1 = Ph
3b 90
(1 : 0.8)
R2 = CH2vCH
12d
R1 = 4-MeC6H5
R2 = CH3
3l
30 (1 : 1)
3
4
R1 = Ph
3c 72 (1 : 1)
3d 64 (1 : 1)
R2 = PhCH2
13
R1 = 4-
3m Trace
R1 = R2 = Ph
MeOC6H5
R2 = CH3
5
6
R1 = Ph
3e 27
R2 = BrCH2
(1 : 0.5)
a Standard reaction conditions: 1 mmol 1, 0.1 mmol PTSA and 1 mmol
iodine in 1 mL nitrile, 0 °C to rt, 24 h. b Isolated yields; the ratio of two
diastereoisomers determined by 1H NMR was given in parenthesis.
c 1 mL DCM was added. d The reaction was carried out in 30 mol%
SnCl2 instead of PTSA.
R1 = 4-FC6H4
R2 = CH3
3f
71 (1 : 1)
best yield at 68% (Table 1, entry 7) for the desired product 3a
and the polymer of styrene was the major byproduct.
7
8
R1 = 4-ClC6H4
R2 = CH3
3g 62 (1 : 1)
Investigating the effect of catalyst loading revealed that
10 mol% PTSA afforded the product in much lower yield and
25 mol% PTSA gave almost the same yield as 20 mol%
(Table 1, entries 10 and 11). The studies on the reaction tempera-
ture showed that 0 °C to rt was optimal. The presence of 1.2
equiv of water in the reaction mixture gave the same result of
using commercial reagent grade CH3CN (Table 1, entry 12). The
use of dichloromethane (DCM) as solvent led to a lower yield in
44% (Table 1, entry 13). Hence, the best conditions are shown in
Table 1, entry 7.
R1 = 4-BrC6H4
3h 74
R2 = CH2vCH
(1 : 0.5)
The generality of this reaction was then examined and these
results were listed in Table 2. The scope of the reaction disclosed
herein appeared to be quite broad with regard to the nitrile
partner, and a variety of nitriles were found to react with styr-
enes. Especially for acrylonitrile 2b, a 90% yield of desired
product 3b was obtained. Moreover, the effect of substituents on
the aromatic ring was also investigated. The corresponding
product 3 was formed in moderate to good yields when the aro-
matic ring contained an electron-withdrawing group. However,
the electron-rich vinylarenes reacted reluctantly (Table 2, entries
11–13), and the corresponding 2-iodo-1-arylethanol and polymer
of aryl alkenes were collected as byproducts.
9
R1 = 4-BrC6H4
R2 = CH3
3i
3j
42
(1 : 0.7)
10
R1 = 4-BrC6H4
R2 = Ph
54
(1 : 0.9)
When TEMPO (1 mmol) was added in this reaction system, it
was found that the yield of the desired product 3a dropped to 5%
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a series of functionalized products could be synthesized from
readily available starting materials in one step. The preliminary
results suggested that the major reaction pathway might be a
combination of cationic dimerization and Ritter reaction for the
domino process, while a competitive radical procedure might be
involved also. Further studies towards a deeper insight into the
reaction mechanism, substrate scope and the stereoselective syn-
thesis are currently ongoing in our group.
Scheme 1 Products of the reaction carried out in the presence of
TEMPO.
Acknowledgements
We are grateful to the National Natural Science Foundation of
China (Grant 20972055, 21172080) and the Fundamental
Research Funds for the Central Universities (Grant
2011ZZ0005).
Notes and references
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Scheme 2 Products of the reaction carried out in the presence of
2 For selected reviews, see: (a) T.-L. Ho, Tandem Organic Reactions, Wiley,
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Scheme 3 Proposed mechanism for the iodine mediated/Brønsted
acid-catalyzed dimerization reaction.
along with the recovery of 15% of styrene 1a. Other than com-
pounds 4 and 5, some unidentified products were also observed
(Scheme 1). For the reaction in the presence of hydroquinone
(1 mmol), the desired product 3a was obtained in 20% yield
with 30% of styrene recovered. Meanwhile, 4 and some uniden-
tified compounds were also observed in the mixture (Scheme 2).
At the current stage, the precise reaction mechanism is not
clear yet. It was tentatively proposed that the major reaction
pathway might be initiated by an electrophilic halogenation reac-
tion at a carbon–carbon double bond,7 followed by a cationic
dimerization to produce 8, which was subsequently trapped by
the solvent acetonitrile in a manner analogous to the Ritter reac-
tion8 to furnish the desired dimer 3a (Scheme 3). In addition, the
radical process might not be neglected, based on the control
reaction results in Schemes 1 and 2.
5 CCDC 838337 (3a) contains the supplementary crystallographic data for
this paper†.
6 As determined by 1H NMR, the sample subjected to X-ray diffraction
study was the one of the major isomers, N-((1R*,3S*)-4-iodo-1,3-diphe-
nylbutyl)acetamide, see the ESI.†.
7 (a) A. Sakakura, A. Ukai and K. Ishihara, Nature, 2007, 445, 900;
(b) H. Ishibashi, K. Ishihara and H. Yamamoto, J. Am. Chem. Soc., 2004,
126, 11122; (c) R. A. Yoder and J. N. Johnston, Chem. Rev., 2005, 105,
4730; (d) A. X. Huang, Z. Xiong and E. J. Corey, J. Am. Chem. Soc.,
1999, 121, 9999.
8 (a) J. J. Ritter and P. P. Minieri, J. Am. Chem. Soc., 1948, 70, 4045; (b) J.
J. Ritter and J. Kalish, J. Am. Chem. Soc., 1948, 70, 4048; For a recent
review,: see: (c) A. Guérinot, S. Reymond and J. Cossy, Eur. J. Org.
Chem., 2012, 19.
Conclusions
We have developed a new iodine mediated and PTSA catalyzed
head-to-tail dimerization reaction of vinylarenes, through which
3612 | Org. Biomol. Chem., 2012, 10, 3610–3612
This journal is © The Royal Society of Chemistry 2012