Oxidant- and additive-free simple synthesis of 1,1,2-triiodostyrenes by one-pot decaroboxylative iodination of propiolic acids

Article abstract of DOI:10.1016/j.tetlet.2020.152378

A metal- and oxidant-free facile synthesis of a range of 1,1,2-triiodostryrene derivatives has been developed which utilizes a simple decarboxylative triiodination of propiolic acids using molecular iodine and sodium acetate in a one-pot manner. Electron-

Full text of DOI:10.1016/j.tetlet.2020.152378

Tetrahedron Letters 61 (2020) 152378
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Oxidant- and additive-free simple synthesis of 1,1,2-triiodostyrenes
by one-pot decaroboxylative iodination of propiolic acids
⇑
Subhankar Ghosh, Rajat Ghosh, Shital K. Chattopadhyay
Department of Chemistry, University of Kalyani, Kalyani 741235, WB, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A metal- and oxidant-free facile synthesis of a range of 1,1,2-triiodostryrene derivatives has been devel-
oped which utilizes a simple decarboxylative triiodination of propiolic acids using molecular iodine and
sodium acetate in a one-pot manner. Electron-withdrawing or donating substituents in the aryl rings dis-
play marginal influence on the course of the reaction. Mechanistic investigation reveals that the reaction
proceeds via a mono-iodo alkyne derivative which subsequently adds an iodine molecule to provide the
title compounds. On the other hand, b,b-diarylacrylic acids, under identical conditions undergo only
decarboxylative mono-iodinaion to provide 1,1-diaryl-2-iodoalkenes, which do not undergo further iod-
ination. The scope of the latter reaction was also examined.
Received 10 June 2020
Revised 12 August 2020
Accepted 15 August 2020
Available online 18 August 2020
Keywords:
Propiolic acids
Iodine
Halogenations
Decarboxylative
Synthetic methods
Ó 2020 Elsevier Ltd. All rights reserved.
Introduction
considerable progress has been made, many of these methods
employ expensive metal catalysts and/or hazardous oxidants or
Haloalkenes represent an important class of building blocks in
organic synthesis ranging from natural products to functional
molecules [1]. These have gained much prominence largely due
to developments in metal-catalyzed cross-coupling reactions for
the creation of carbon–carbon and carbon-hetero bond formation.
As a result, a large number of methodologies have been developed
for rapid access to haloalkenes [2]. Polyhaloalkenes serve similarly
as step-economic means for poly-functionalization of alkene
derivatives related to the preparation of materials of optical and
electronic interest [3]. Due to greater reactivity, the vinyl polyio-
dides and polybromides have seen majority of the applications
and thus, several methodologies have been developed for the syn-
thesis of such kind of alkenes. The terminal acetylenes have
remained the major source since well-defined and elegant halo-
genation techniques employing iodine and an oxidant such as PhI
(OAc)2 [4] Oxone [5], and DMSO [6] have been developed. The clas-
sical Hunsdiecker-type decarboxylative halogenation of propiolic
acids is an important methodology [7,8] for traceless conversion
for direct access to vinyl monohalides and dihalides (halogen = Cl,
Br, I). A recent achievement is the oxidative tribromination of phe-
nyl propiolic acids [9]. Triiodination of phenyl propiolic acid with
I2O5 as oxidant has been observed as a side reaction during prepa-
ration of triiodo ketones from aryl propiolic acids [10]. Though
reagents (Scheme 1).
Thus, need for the development of a simple route for the syn-
thesis of triiodo styrenes employing easily available precursors
and simple reagents is of importance. Herein, we describe an oxi-
dant-, additive, and metal-free synthesis of triiodostyrenes by
decarboxylative triiodination of phenyl propiolic acid, in continua-
tion of our interest on iodine-mediated transformations [11].
Results and discussion
When the decarboxylative iodination of phenyl propiolic acid
was attempted using two equivalents each of iodine and sodium
acetate using acetonitrile as solvent, little conversion took place
and a mixture of inseparable products formed [entry 1, Table 1].
Increasing the equivalence of iodine to three did not accelerate
the conversion much at room temperature while under refluxing
conditions, a complex mixture of products formed. On the other
hand, when six equivalents of iodine was used together with two
equivalents of sodium acetate (entry 3) at room temperature, a
slow but steady conversion took place and the desired product 2
was obtained in 87% yield within 16 h. Use of two equivalents of
base seemed to be optimal, since when the equivalents were
reduced to one (entry 4), or one and a half (entry 5) lower yields
were obtained. Similarly, with further addition of base (3/4 equiv.,
entry 6, 7) little improvement of yield was noticed. Attempts to
reduce the reaction time by refluxing in acetonitrile indeed
⇑
Corresponding author.
E-mail address: skchatto@yahoo.com (S.K. Chattopadhyay).
https://doi.org/10.1016/j.tetlet.2020.152378
0040-4039/Ó 2020 Elsevier Ltd. All rights reserved.

2
S. Ghosh et al. / Tetrahedron Letters 61 (2020) 152378
marginally successful (entry 15). However, further increase of tem-
perature (entry 16) proved to be deleterious when the desired pro-
duct was not seen at all; the fate being formation of a dark mixture
of several products. When methanol was used as solvent, the con-
version was somewhat lower (entry 17, 60%) at room temperature
which marginally improved on refluxing (70%). The starting mate-
rial was recovered (10–15%) in both the cases. Interestingly, when
N-iodosuccinimide was used as the iodinating agent (entry 18)
only Hunsdiecker-type decarboxylative mono-iodination took
place even when six equivalents of the reagent was used. Thus,
the entry 3 was accepted as the optimised condition for the study
of scope and limitation of the reaction 1 ? 2 (Scheme 2).
The reaction proceeds well with substrates having one methyl
substituent at para-, ortho- or meta positions (2b–d, Fig. 1) or
two such substituent (2e, f) with little difference in yields. Similar
results were also obtained with methoxy–substituted iodoarenes
resulting in compounds (2g–i). Moreover, electron withdrawing
substituents such as fluorine (2j–l), chlorine (2m, n), nitro (2o, p)
and trifluoromethyl (2q, r) also behaved analogously in terms of
rate and yield of product in each case. The 1-naphthyl ring system
(2s) and the hetero-aromatic derivative (2t) were prepared in good
yields under analogous conditions. Thus, the reaction appears to
tolerate a good variety of electron donating and withdrawing sys-
tems as well as applicable to polyaromatic and heteroaromatic
substrates.
Scheme 1. Previous and present work.
Table 1
Optimization of the conversion 1 ? 2.
Entry Reagents (eqv) Conditions
2 (2equiv) /NaOAc (2) MeCN, rt, 16 h
% 2
1
2
I
Mixture of
products
I2 (3) /NaOAC (2)
MeCN, rt to reflux, 6 h Mixture of
products
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
I2 (6)/ NaOAc (2)
I2 (6)/ NaOAc (1)
I2 (6)/ NaOAc (1.5)
I2 (6)/ NaOAc (3)
I2 (6)/ NaOAc (4)
I2 (6)/NaOAc (2)
I2 (9)/NaOAc (2)
I2 (6)/ KOAc (2)
I2/ n-Bu4N+ OAc-(2)
I2 (6)/ K2CO3 (2)
I2 (6)/ Cs2CO3 (2)
I2 (6)/ NaOAc (2)
I2 (6)/ NaOAc (2)
I2 (6)/ NaOAc (2)
I2 (6)/ NaOAc (2)
NIS (6)/ NaOAC (2)
MeCN, rt, 16 h
MeCN, rt, 16 h
MeCN, rt, 16 h
MeCN, rt, 16 h
MeCN, rt, 16 h
MeCN, reflux, 2 h
MeCN, reflux, 2 h
MeCN, rt, 16 h
MeCN, rt, 16 h
MeCN, rt, 16 h
MeCN, rt, 16 h
DMSO, rt, 16 h
DMSO,50 °C, 16 h
DMSO, 90 °C, 8 h
MeOH, rt, 16 h
MeCN, rt, 16 h
87
61
78
84
88
65
72
84
79
77
74
60
71
Complex mixture
60
3 (62%)
resulted in accelerated conversion but a lower yield of the product
2 (65%) was obtained within two hours (entry 8). Increasing the
loading of iodie to nine equivalent, somewhat improved the yield
of 2 to 72% (entry 9). But purification of the product was a little
more challenging. Changing the base from sodium acetate to
potassium acetate or tetrabutylammonium acetate did not signifi-
cantly alter the course of the reaction (entries 10 and 11). More or
less similar conversion was noticed when potassium carbonate
(entry 12) or cesium carbonate (entry 13) were also used as bases.
Similarly, when the solvent was changed to DMSO, little drop in
yield was observed under otherwise analogous conditions (entry
14). Attempts to optimize the conditions by heating at 50 °C were
Scheme 2. Mechanistic studies.

S. Ghosh et al. / Tetrahedron Letters 61 (2020) 152378
3
Table 2
Optimization of the conversion 6 ? 7.
Entry
Reagents (eqv)
Conditions
% 7
1
2
3
4
5
6
7
8
I2 (6equiv) /NaOAc (2)
I2 (1equiv) /NaOAc (1)
I2 (1equiv) /NaOAc (1)
I2 (2equiv) /NaOAc (1)
I2 (3equiv) /NaOAc (1)
I2 (4equiv) /NaOAc (1)
I2 (4equiv) /NaOAc (2)
I2 (5equiv) /NaOAc (2)
I2 (6equiv) /NaOAc (2)
I2 (6equiv) /KOAc (2)
I2 (6equiv) /K2CO3 (2)
I2 (6equiv) /NaOAc (2)
MeCN, rt, 16 h
MeCN, rt, 5 h
81%
Trace
15
22
27
32
57
68
53
MeCN, rt, 16 h
MeCN, rt, 16 h
MeCN, rt, 16 h
MeCN, rt, 16 h
MeCN, rt, 16 h
MeCN, rt, 16 h
MeCN, reflux, 6 h
MeCN, rt, 16 h
MeCN, rt, 16 h
CH2Cl2, rt, 16 h
9
10
11
12
72
69
71
Table 3
Substrate scope for the conversion 6 to 7.
Fig. 1. Substrate scope of the eaction 1 ? 2.
Compound
R1, R2
Yield of 7 (%)
Towards understanding the mechanistic possibilities, it was
observed that probably the reaction proceeds through the interme-
diate formation [12] of the decarboxylative iodination product 3
since the later delivered the triiodo compound 2 when separately
treated with iodine (five equiv.) under analogous conditions. The
diiodination of 3 may proceed through an open-cation 4 or the cyc-
lic iodonium ion 5 [14]. However, when the ß,ß-disubstituted
iodoalkene 7, prepared from the decarboxylative iodination of ß-
phenylcinnamic acid, under analogous conditions did not undergo
further iodination even with six equivalent iodine. Thus, the pres-
ence of a further cation- stabilizing phenyl group has little influ-
ence and the reaction may involve other pathways also. It is
possible that the addition perhaps proceeds under steric control.
The possibility of involvement of radicals also looks remote based
on the fact that when the reaction was conducted in the presence
of radical quencher like TEMPO or BHT, the reaction proceeded
similarly but in somewhat reduced yields.
We further investigated for the scope and optimization of con-
ditions of the transformation 6 ? 7 (Scheme 3) in view of a similar
report [13]. Although the reaction was first observed as a side reac-
tion, it appeared that, this was the condition of choice since
attempted searches for use of lesser equivalents of iodine and base
(entries 2–8, Table 2), shorter reaction time (entry 9), change of
base to KOAc/K2CO3 (entries 10, 11) and use of DCM as solvent (en-
try 12) all proved to be somewhat less effective for the synthesis of
7. Thus, the use of excess iodine seems to be crucial. The conver-
6a, 7a
6b, 7b
6c, 7c
6d, 7d
6e, 7e
6f, 7f
R1 = R2 = H
81
84
76
88
71
68
74
70
65
R1 = Me; R2 = H
R1 = CMe3; R2 = H
R1 = F; R2 = H
R1 = Cl; R2 = H
R1 = H; R2 = OMe
R1 = H; R2 = Me
R1 = H; R2 = Cl
6 g, 7 g
6 h, 7 h
sion has previously been attempted [13] in substrates having an
obligatory methoxy substituent in either of the phenyl rings. How-
ever, under the presently developed conditions, substrates con-
taining substituents such as methyl, methoxy, chlorine, fluorine
or a tert-butyl group as well as unsubstituted phenyl ring (com-
pounds 6a–I, Table 3) all proceeded with more or less equal ease
and similar yields under the optimised conditions. Moreover, the
substrate 6i containing a methyl substitution in place of the second
aryl ring also behaved analogously. The substrates may be consid-
ered important in view of the possibility of further functionaliza-
tion through metal catalyzed cross-coupling reactions [15].
Conclusion
In conclusion, a simple synthesis of 1,1,2-triiodostyrenes has
been developed by decarobxylative iodination of using molecular
iodine and a simple base. The reaction tolerates the presence of
both electron withdrawing and electron donating functional
groups. An interesting extension is the preparation of the ß,ß-
diaryliodoalkenes 7a–i of potential applications. The methodology
may thus complement the existing literature and hence find
applications.
Scheme 3. Formation of compound 7 from 6.

4
S. Ghosh et al. / Tetrahedron Letters 61 (2020) 152378
[4] (a) Y. Liu, D. Huang, J. Huang, K. Maruoka, J. Org. Chem. 82 (2017) 11865–
Declaration of Competing Interest
11871. (b) Y. Li, D. Huang, J. Huang, K. Maruoka, JOVE139 (2018) e 58063.
[5] V. Sriramoju, R. Jillella, S. Kurva, S. Madabhushi, Chem. Lett. 46 (2017) 560–
562.
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared
to influence the work reported in this paper.
[6] S.A. Rather, A. Kumarab, Q.N. Ahmed, Chem. Commun. 55 (2019) 4511–4514.
[7] For some early reports, see; (a) D. Naskar, S. Roy, J. Org. Chem. 64 (1999) 6896–
6897. (b) D. Naskar, S. Roy, Tetrahedron 56 (2000) 1369–1377. (c) J.P. Das, S.
Roy, J. Org. Chem. 67 (2002) 7861–7864. (d) G.W. Kabalka, A.R. Mereddy,
Tetrahedron Lett. 45 (2004) 1417–1419. (e) C. Kuang, Q. Yang, H. Senboku, M.
Tokuda, Synthesis (2005) 1319–1325. (f) S. Stavber, M. Jereb, M. Zupana,
Synthesis (2008) 1487–1513. (g) P. Pawluc´, G. Hreczycho, J. Szudkowska, M.
Kubicki, B. Marciniec, Org. Lett. 11 (2009) 3390–3393.
[8] For some recent reports, see: (a) Z. Wang, L. Zhu, Z. Su, Z. Li, C. Li, J. Am. Chem.
Soc. 134 (2012) 4258–4263. (b) A. Jayaraman, E. Cho, F.M. Irudayanathan, J.
Kim, S. Lee, Adv. Synth. Catal. 360 (2018) 130–141. (c) L. Pfeifer, V. Gouverneur,
Org. Lett. 20 (2018) 1576–1579. (d) Kiyokawa, T. Kojima, Y. Hishikawa, S.
Minakata, Chem. Eur. J. 21 (2015) 15548–15552. (e) A.B. Borah, G. Yan, Org.
Biomol. Chem. 13 (2015) 8094–8115. (f) D. Resch, C.H. Lee, S.Y. Tan, L. Luo, N.S.
Goroff, Eur. J. Org. Chem. (2015) 730–737. (g) C. Chen, J. Wu, G. Yan, D. Huang,
Tetrahedron Lett. 61 (2020) 151415.
Acknowledgments
We are thankful to DST, New Delhi, for funds
(EMR/2017/001336).
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tetlet.2020.152378.
[9] A. Jayaraman, E. Cho, J. Kim, S. Lee, Adv. Synth. Catal. 360 (2018) 3978–3989.
[10] M.J. Cohen, E. McNelis, J. Org. Chem. 49 (1984) 515–518.
[11] S. Ghosh, S.K. Chattopadhyay, Adv. Synth. Catal. 361 (2019) 4727–4738.
[12] see: M. yao, J. Zhang, S. Yang, E. Liu, H. Xiong, Synthesis of 1-iodoalkynes has
been recently described Synlett (2020) 000, https://doi.org/10.1055/S-0040-
1708002.
References
[1] J. Tsuji, Reactions of Organic Halides and Pseudohalides, Transition Metal
Reagents and Catalysts: InnoVations in Organic Synthesis, Wiley, New York,
2000, pp. 27–108.
[2] (a) For some reviews, see: G. Chelluci Chem. Rev. 112 (2012) 1344–1462;
(b) A. Idris, S. Lee, Synthesis (2020), https://doi.org/10.1055/s-0040-1707600.
[3] (a) For some recent reports, see: K. Iida, S. Ishida, T. Watanabe, T. Arai J. Org.
Chem. 84 (2019) 7411–7417;
[13] J. Li, H. Chen, D.Z. Negrerie, Y. Du, K. Zhao, RSC Adv. 3 (2013) 4311–4320.
[14] P. Bassi, U. Tonellato, J. Chem. Soc. Perkin Trans. 2 (1974) 1283–1288.
[15] General procedure for the synthesis of 1,1,2-Triiodostyrenes (2a-t): To
a
solution of phenylpropiolic acid (50mg, 0.34mmol), sodium acetate (56mg,
0.68mmol) in CH3CN (3ml) was added molecular iodine (520mg, 2.05mmol)
and the resulting mixture was stirred at room temperature for 16 h when the
reaction was complete. It was then diluted with water (10ml) and extracted
with ethyl acetate (2Â20ml). The combined organic extract was washed with
sat aq solution of Na2S2O3 (2 Â 10 mL), H2O (10 mL), brine (10 mL), and then
dried (MgSO4). It was then filtered and the filtrate was concentrated under
(b) N. Taniguchi, Tetrahedron 74 (2018) 1454–1460;
(c) D.S. Rao, T.R. Reddy, S. Kashyap, Org. Biomol. Chem. 16 (2018) 1508–1518;
(d) Y. Li, X. Liu, D. Ma, B. Liu, H. Jiang, Adv. Synth. Catal. 354 (2012) 2683–
2688;
(e) J. Chen, S.-X. Su, D.-C. Hu, F.-H. Cui, Y.-L. Xu, Y.-Y. Chen, X.-L. Ma, Y.-M. Pan,
Y. Liang, Asian J. Org. Chem. 7 (2018) 892–896;
reduced pressure to leave
a residue which was purified by column
(f) J. Xiao, L.-B. Han, Tetrahedron Lett. 75 (2019) 3510–3515;
(g) Q. Jiang, J.-Y. Wang, C.-C. Guo, Synthesis 47 (2015) 2081–2087;
(h) J.M. Timonen, P.A. Turhanen, ACS Omega. 4 (2019) 14663–14668;
(i) R. Banothu, S. Peraka, S. Kodumuri, D. Chevella, K.S. Gajula, V. Amrutham, D.
R. Yennamaneniab, N. Nama, New J. Chem. 42 (2018) 17879–17883;
(j) S. Madabhushi, R. Jillella, K.K.R. Mallu, K.R. Godala, V. Vangipuram, S,
Tetrahedron Lett. 54 (2013) 3993–3996;
(k) M. Yao, J. Zhang, S. Yang, H. Xiong, L. Li, E. Liua, H. Shia, RSC Adv. 10 (2020)
3946–3950;
(l) M. Jereb, M. Zupana, S. Stavberb, Chem. Commun. (2004) 2614–2625;
(m) S. Ni, W. Sha, L. Zhang, C. Xie, H.J. Mei, Y. Han, Pan Org. Lett. 18 (2016)
712–715.
chromatography on silica gel (petroleum ether) to provide the 1-(1,2,2-
triiodovinyl)benzene (2a) 4,5,6 as a pale yellow solid; yield 143mg (87%); IR
(neat):3434, 2922, 2851, 1725, 1637 cm-1; 1H NMR (400 MHz, CDCl3) d (ppm)
7.38- 7.30 (3H, m), 7.27-7.25 (2H, m); 13C NMR (100 MHz, CDCl3) d (ppm)
147.7, 128.7, 128.6, 127.4, 112.5, 22.6. 1-(2-iodoethynyl)benzene (3)4. This
was prepared following the general procedure but we using I2 (194mg, 0.77
mmol) and stirring the reaction mixture for 2h. Pale yellow viscous liquid;
yield 49 mg (62%); IR (neat): 3435, 2923, 2851, 1724, 1636 cm-1; 1H NMR
(400 MHz, CDCl3) d 7.37-7.35 (2H, m), 7.28-7.22 (3H, m); 13CNMR (100 MHz,
CDCl3) d (ppm) 132.33, 128.8, 128.2, 123.4, 94.1, 6.2.