Iodine Monoacetate for Efficient Oxyiodinations of Alkenes and Alkynes

Article abstract of DOI:10.1055/s-0036-1589119

A novel and inexpensive, environmentally friendly method for the preparation of iodine monoacetate is presented using iodine and Oxone in acetic acid/acetic anhydride. The reagent is used in a highly efficient approach for the regio- and diastereoselective iodo-acetoxylation of alkenes and alkynes in a simple one-pot process.

Full text of DOI:10.1055/s-0036-1589119

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© Georg Thieme Verlag Stuttgart · New York
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Iodine Monoacetate for Efficient Oxyiodinations of Alkenes and
Alkynes
Tobias Hokampa
OAc
R
R
I
OAc
Alena Therese Storma
Mekhman Yusubovb
Thomas Wirth*a
R''
R''
R'
R'
I
30 examples
up to 98% yield
R = aryl, heteroaryl, alkyl
R' = aryl, alkyl, Br, H
a School of Chemistry, Cardiff University, Park Place, Cardiff,
CF10 3AT, UK
wirth@cf.ac.uk
b Tomsk Polytechnic University and Siberian State Medical
University, 634050 Tomsk, Russia
R'' = alkyl, CO2Et, COPh, CN, H
one-pot synthesis
regio- and diasteroselectivity
green chemistry
Published as part of the Cluster Alkene Halofunctionalization
Received: 06.09.2017
Accepted after revision: 27.09.2017
Published online: 20.10.2017
thesis of α-iodinated ketones9 or to prepare iodohydrins
and iodoesters from alkenes10 and, in combination with so-
dium iodide, to make α-aryl ketones from arylalkenes.11
We started our investigation to form iodine monoace-
tate using iodine and Oxone in acetic acid/acetic anhydride.
The success of the reaction was indicated by a subsequent
reaction with styrene (1a) as test substrate which reacts in
an iodoacetoxylation to 2a. Best results for the iodoacetoxy-
lation were achieved by treatment of iodine with two
equivalents of Oxone in a mixture of acetic acid and acetic
anhydride at 50 °C for 21 hours. After addition of styrene
(1a, 2 equiv) and two hours reaction time at room tempera-
ture, only the Markovnikov product 2a was obtained in 84%
yield in this one-pot synthesis. Further optimisation exper-
iments such as concentration of the reagents and reaction
times are described in the Supporting Information (Table
S1). An iodoacetoxylation in the absence of acetic anhydride
did not provide 2a and with traces of acetic acid in acetic
anhydride a much longer reaction time and a higher
amount of Oxone were necessary, indicating that both, ace-
tic acid and acetic anhydride, are required for the success of
this reaction. The reaction scope with iodine monoacetate
was explored with different arylalkenes (Scheme 2). The
phenyl-substituted aromatic ring in 1b did not affect the
yield of 2b (79%) and also 2-vinylnaphthalene (1c) provided
2c with good yield (74%). A chlorine substituent in 3-posi-
tion led to an almost quantitative yield of 2d (98%), whereas
substitution in 2-position gave 83% of 2e together with the
corresponding iodohydrin (4%). Furthermore, 2,6-dichloro-
styrene (1f) gave similar yield (79%). Strong electron-with-
drawing groups such as fluoro (2g) and nitro substituents
(2h) reduced the yield to 70%, whereas a methyl substituent
did not affect the outcome of the reaction (2i, 79%). After-
wards, the effect of substituents in α-position was investi-
gated. A high yield was achieved for the iodoacetoxylation
of 1j with a phenyl substituent in α-position (2j, 91%), a
DOI: 10.1055/s-0036-1589119; Art ID: st-2017-r0670-c
Abstract A novel and inexpensive, environmentally friendly method
for the preparation of iodine monoacetate is presented using iodine
and Oxone in acetic acid/acetic anhydride. The reagent is used in a
highly efficient approach for the regio- and diastereoselective iodo-
acetoxylation of alkenes and alkynes in a simple one-pot process.
Key words alkenes, alkynes, iodine, iodine(I)acetate, oxyiodination
Iodine monoacetate is an important reagent for the
functionalisation of alkenes, alkynes, and ketones.1 It has
been reported to be easily accessible from an equimolar
mixture of silver acetate and iodine,2 and higher homo-
logues of the reagent have been made from silver carboxyl-
ates and iodine for the synthesis of aliphatic esters.3 How-
ever, iodine monoacetate has not yet been isolated and has
only been characterised by 1H NMR spectroscopy4 and
spectrophotometrically.5 As silver acetate is an expensive
reagent, there are alternative ways of generating iodine
monoacetate. It can be prepared from very toxic mercuric
acetate,6 lead tetraacetate,7 peracetic acid,8 or (diacetoxy-
iodo)benzene4 by reaction with iodine.
Herein, we report a novel method for the synthesis of io-
dine monoacetate using elemental iodine and Oxone in com-
bination with acetic anhydride and acetic acid (Scheme 1).
Oxone
I2
2 IOAc
Ac2O/AcOH
Scheme 1 Formation of iodine monoacetate using iodine and Oxone
Oxone is an inexpensive and environmentally safe oxi-
dant which is known to oxidise iodine salts such as ammo-
nium iodide to iodine(I). This has been explored in the syn-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–D

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T. Hokamp et al.
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methyl substituent gave 71% yield of 2k. An inseparable
mixture of ketones 2l and 2m (1.25:1) was obtained using
α-bromostyrene as starting material.
The reactivity of nonconjugated alkenes with iodine
monoacetate was explored (Scheme 3). As expected, allyl-
benzene 3a provided a mixture of regioisomers and the
Markovnikov product 4a and anti-Markovnikov product 5a
were obtained in almost equal amounts (35% and 32%). A
larger excess of Markovnikov product (1.5:1) was obtained
with a methoxy substituent in 4-position (3b) to give 4b
and 5b in 40% and 27% yield, respectively. 1-Hexene (3c)
gave a better regioselectivity and 4c/5c in 42% combined
yield (4c/5c = 2:1). Furthermore, 1,5-hexadiene (3d) pro-
vided diastereomers of product 4d (12%) and 5d in addition
to a third regioisomer (27% combined yield). Surprisingly,
2-methyl-3-buten-2-ol (3e) led to the rearranged product
5e (40%).12 Alkenes 3f and 3g were functionalised in mod-
erate yields to exclusively 5f (46%) and 5g (38%).
1) Oxone (2 equiv)
OAc
Ac2O (32 equiv), AcOH (105 equiv)
50 °C, 21 h
R
R'
I2
Ar
R
2)
(1.6 equiv)
R'
I
r.t., 2 h
Ar
2a–t
1a–t
Ar = aryl, heteroaryl
R = Ph, alkyl, Br, H
R' = alkyl, CO2Et, COPh, CN, H
OAc
OAc
OAc
I
I
I
R
2a (84%; R = H)a
2b (79%; R = 4-Ph)
R
2c (74%)
2d (98%; R = 3-Cl)
2e (83%; R = 2-Cl)b
1) Oxone (2 equiv)
Ac2O (32 equiv)
AcOH (105 equiv)
AcO Ph
AcO Me
2f (79%; R = 2,2-Cl2)
2g (70%; R = 2,3,4,5,6-F5)
2h (70%); R = 3-NO2)c
2i (79%); R = 2-Me)
I
I
Ph
Ph
OAc
I
50 °C, 21 h
2j (91%)
2k (71%)
I2
I
OAc
5a–g
(1.6 equiv)
r.t., 2 h
+
2)
OAc
O
OAc
R
R
R
O
4a–g
3a–g
CN
Ph
X
Ph
OEt
R = alkyl
Ph
2l (X = I)
2m (X = Br)
(inseparable mixture, 70%)
I
I
2n (64%)d
OAc
2o (34%)e
I
OAc
OAc
I
OAc
4a (35%)
I
Ph
5a (32%)
I
AcO
I
I
OAc
OAc
I
MeO
I
MeO
2p (72%)
2q (53%)
2r (57%)
4b (40%)
5b (27%)
OAc
I
OAc
O
OAc
I
AcO
Ph
Ph
N
I
4c
5c
(inseparable mixture, 42%)
I
2t (70%)f
2s (88%)
OAc
Scheme 2 Substrate scope for the iodoacetoxylation of styrene deriva-
tives (0.5 mmol I2, 1 mmol Oxone, 0.8 mmol alkene in Ac2O (1.5 mL)
and AcOH (3.0 mL). a 2.0 equiv of 1a were used; b the corresponding
iodohydrin was isolated in 4% yield; c iodohydrin was isolated in 26%
yield; d recovery of 8% starting material e 4 d reaction time; recovery of
59% starting material; f recovery of 10% starting material.
I
AcO
I
OAc
OAc
OAc
I
4d (12%)a,b
5d (27%)a,c
Me
Cl
MeO
OMe
OAc
5f (46%)
AcO
Me
OH
Me
I
I
I
5g (38%)
5e (40%)
Next, the influence of substituents in the β-position was
investigated. To our delight, reactions of ethyl cinnamate
(1n) and cinnamonitrile (1o) demonstrated the tolerance of
substituents in the β-position to give regio- and diastereo-
selective iodoacetoxylation providing the trans-product 2n
in good yield (64%). However, the cyanide substituent slows
down the reaction. After a reaction time of four days 2o was
isolated in 34% yield and 59% of 1o recovered. Additionally,
cyclic alkenes such as 1,2-dihydronaphthalene (1p), indene
(1q), or 1-phenyl-1-cyclohexene (1r) can be used in this
one-pot functionalisation to give reasonable yields of com-
pounds 2p, 2q, and 2r (53–72%). The heteroaromatic com-
pound 2-vinylpyridine (1s) was converted in excellent yield
(88%) into 2s and chalcone (1t) gave product 2t in good
yield (70%).
Scheme 3 Substrate scope for the iodoacetoxylation of alkyl-substituted
alkenes. a 0.8 equiv of 3d were used; b mixture of diastereomers; c mixture
of diastereomers of 5d and a third regioisomer.
Interestingly, alkynes also reacted smoothly under the
same reaction conditions in good yields to the iodoacetoxy-
lated products. A mixture of 7a and 8a was obtained by re-
action of phenylacetylene (6a) in 60% combined yield (Table
1). Compound 8a is the result of a second iodoacetoxylation
of 7a followed by ketal cleavage. On the contrary, 1-phenyl-
1-propyne (6b) led exclusively to product 7b (71%) and 1-
hexyne (6c) gave only the diiodoketone 7c in 73% yield.
Compound 6d did not react in the expected way and the
diiodinated product 7d was obtained (39%) as verified by
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–D

C
T. Hokamp et al.
Cluster
Synlett
literature spectra.13 Additionally, propiophenone (6e) could
be iodinated in the α-position to give 7e in good yield (70%).
Compound 8e was obtained as side product in 5% yield.
O
1) Oxone (2 equiv)
Ac2O (32 equiv)
D3CCO2D (105 equiv)
50 °C, 21 h
O
CD3/CH3
Cl
I2
2) 1d (1.6 equiv)
r.t., 2 h
I
2d (D/H = 2:1)
Table 1 Reaction of Iodine Monoacetate with other Substrates
Entry
Substrate
Product(s)
Scheme 4 Iododeuteroacetoxylation of 1d in acetic acid-d4
OAc
O
I
method was illustrated with a broad range of alkenes and
alkynes. Styrene derivatives gave highest yields, whereas al-
lylic and aliphatic olefins produced regioisomeric mixtures
in lower yields. Alkynes led to mono- and diiodinations in
comparable yields. Compared to previous procedures, this
inexpensive, metal-free, and environmentally friendly
method provides high yields and mild reaction conditions.
I
I
1
6a
7a
8a
(inseparable mixture, 60%)
OAc
2
I
6b
6c
7b (71%)
Funding Information
O
Support from the Fonds der Chemischen Industrie (TH), the Erasmus
program (ATS), and the School of Chemistry, Cardiff University, is
gratefully acknowledged. We thank the Russian Foundation for Basic
Research (RFBR-KO_a 16-53-10046) and the Royal Society (IE160304)
for support. Financial support from Tomsk Polytechnic University
I
3
4
I
7c (73%)
I
HO
HO
(VIU-316/2017) is also gratefully acknowledged (MY).
R
o
y
a
l
S
o
ecity
E
I(1
6
0
3
0
4)
I
6d
7d (39%)
Acknowledgment
O
O
O
We thank the EPSRC National Mass Spectrometry Facility, Swansea,
for mass spectrometric data.
5
OAc
I
7e (70%)
8e (5%)
6e
Supporting Information
a BF3·OEt2 (2.4 mmol) was added.
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1589119.
S
u
p
p
o
nrtogI
f
rmoaitn
S
u
p
p
ortiInfogrmoaitn
To further verify the existence of iodine monoacetate,
acetic acid and acetic anhydride were removed and the re-
maining oil was examined, which was protected from
moisture to prevent decomposition, via 1H NMR analysis. A
peak at δH = 2.19 ppm reveals the formation of iodine
monoacetate.4 To get further insight into the role of acetic
acid and acetic anhydride, acetic acid was replaced by deu-
terated acetic acid-d4 followed by reaction with styrene
(Scheme 4). In this case, partial deuteration of product 2a
was observed (D/H = 2:1), which indicates again that both,
acetic acid and acetic anhydride, play an important role in
the formation of iodine monoacetate.
References and Notes
(1) (a) Ginsburg, D. J. Am. Chem. Soc. 1953, 75, 5746. (b) Heasley, V.
L.; Holstein, L. S. III; Moreland, R. J.; Rosbrugh, J. W. Jr.;
Shellhamer, D. F. J. Chem. Soc., Perkin Trans. 2 1991, 1271.
(c) Dhaliwal, G. K.; Wilson, G. J. Rubber Chem. Technol. 1994, 67,
567. (d) Ogata, Y.; Aoki, K. J. Org. Chem. 1966, 31, 1625. (e) Giri,
R.; Yu, J.-Q. Iodine Monoacetate, e-EROS Encyclopedia of Reagents
for Organic Synthesis; John Wiley and Sons: Hoboken, NJ, 2008.
(2) (a) Kleinberg, J. Chem. Rev. 1947, 40, 381. (b) Wilson, C. V. Org.
React. 1957, 9, 332.
(3) (a) Simonini, A. Monatsh. Chem. 1893, 14, 81. (b) Bunce, N. J.;
Murray, N. G. Tetrahedron 1971, 27, 5323.
In conclusion, we have demonstrated a novel and inex-
pensive, environmentally friendly method for the forma-
tion of iodine monoacetate using iodine and Oxone in a
mixture of acetic acid and acetic anhydride. The reagent
was used in a highly efficient approach for the regio- and
diastereoselective iodoacetoxylation of alkenes and alkynes
in a simple one-pot process. Scope and limitation of the
(4) Courtneidge, J. L.; Lusztyk, J.; Pagé, D. Tetrahedron Lett. 1994, 35,
1003.
(5) Barnett, J. R.; Andrews, L. J.; Keefer, R. M. J. Am. Chem. Soc. 1972,
94, 6129.
(6) Chen, E. M.; Keefer, R. M.; Andrews, L. J. J. Am. Chem. Soc. 1967,
89, 428.
(7) Heusler, K.; Kalvoda, J. Angew. Chem., Int. Ed. Engl. 1964, 3, 525.
(8) Ogata, Y.; Aoki, K. J. Am. Chem. Soc. 1968, 90, 6187.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–D

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(9) Reddy, M. M.; Kumar, M. A.; Swamy, P.; Narender, N. Tetrahe-
dron Lett. 2011, 52, 6554.
(10) Durgaiah, C.; Naresh, M.; Kumar, M. A.; Swamy, P.; Reddy, M.
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© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–D