Iodoamidation of olefins with chloramine salts and iodine in aqueous media

Article abstract of DOI:10.1039/c0cc03855e

An efficient, unique, and convenient method for the iodoamidation of olefins with chloramine salts and I₂ in aqueous media is described. This method was applicable to a wide range of olefins, including aromatic, aliphatic, and electron-deficien

Full text of DOI:10.1039/c0cc03855e

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Iodoamidation of olefins with chloramine salts and iodine
in aqueous mediaw
Satoshi Minakata* and Junpei Hayakawa
Received 14th September 2010, Accepted 16th November 2010
DOI: 10.1039/c0cc03855e
An efficient, unique, and convenient method for the iodoamidation
of olefins with chloramine salts and I2 in aqueous media is
described. This method was applicable to a wide range of olefins,
including aromatic, aliphatic, and electron-deficient olefins.
Amidohalogenation reactions, which are in widespread use,
involve the conversion of common petroleum olefins into vicinal
haloamine products via the addition of amide and halogen units
to carbon–carbon double bonds.1 Haloamine derivatives are
versatile synthetic intermediates and can be used in the synthesis
of functional materials and biologically active compounds.2
Among the halogens, iodine is a powerful substituent for
organic transformations such as transition metal-catalyzed,
radical and ionic reactions. Nevertheless, only a few examples
have been reported on the direct iodoamidation of olefins.
Although the use of iodine azide (IN3), prepared by reacting
sodium azide with iodine monochloride, is a well-known
method for the introduction of an iodine atom and a nitrogen
unit into olefins,3 azides require careful handling due to their
high reactivity, explosiveness, and toxicity. Alternative methods
Scheme 1 Strategy for the iodoamidation of olefins.
Although we reported on the iodine-catalyzed aziridination
of olefins using chloramine-T (CT) in organic or aqueous
media,8 no iodoamidated products were obtained under the
reaction conditions. In order to achieve the desired
iodoamidation, a stoichiometric amount of iodine was used.
When styrene was treated with a stoichiometric amount of
iodine and CT in an organic solvent (acetonitrile or n-hexane)
or neat (styrene only), the corresponding aziridine was detected
in the reaction mixture in all cases (Table 1, entries 1–3). On the
contrary, when the reaction was conducted in water, the
iodoamidated compound 1a was obtained in 53% yield with
complete regioselectivity. Iodoamidated compounds could be
prepared by the ring opening of aziridines with iodide, but it is
known that in the case of the ring opening of aziridine 1b with
iodide, the reverse regioisomer is produced, compared with
1a,9 indicating that iodoamidation in water is not involved
in the formation of the aziridine. Thus, this present
iodoamidation and ring opening of aziridines with iodide can
be regarded as a complementary method for the formation of
iodoamidated compounds. Unexpectedly, bromamine-T was
not effective for the reaction.
4a
4b
for iodoamidation using I(py)2BF4 or I2 as iodine sources
were developed by Barluenga’s and Corey’s groups. Since the
products as well as the transformations are very useful, Corey’s
group successfully used the method for a key step of
the synthesis of the anti-influenza neuramidase inhibitor,
oseltamivir.4c These methods are very valuable, but stoichio-
metric or larger amounts of HBF4 or SnCl4 are required, the
nitrogen source is restricted to the reaction solvent (acetonitrile),
and only cyclohexene derivatives were employed as substrates.
Thus, more practical and efficient iodoamidation is desired.
We previously reported on the chloro-5a and bromoamidation5b
of olefins using haloamine-T under an atmosphere of CO2. We
hypothesized that a unique reaction is induced by the insertion of
CO2 into the N–Na bond of haloamine-T, and this species then
generates a cyclic halonium intermediate on the reaction with an
olefin. Based on the proposed mechanism, a general and facile
iodoamidation was devised as follows. Haloamine-T reacts with
iodine to give N-halo-N-iodo-p-toluenesulfonamide.6 Among the
three substituents on the nitrogen, the iodo substituent would act
as an iodonium ion because of its low electronegativity
(Scheme 1). Based on this scenario, we report herein on the
iodoamidation of olefins using chloramine salts and iodine in an
aqueous media.7
In order to improve the efficiency of the iodoamidation, the
reaction conditions were optimized. The use of two equivalents
of CT increased the yield of the product to 73% (Table 2, entry 1).
The addition of a small amount of n-hexane (100 mL), almost
the same volume as styrene, resulted in a further improvement
in the efficiency (Table 2 entry 1). The reaction of styrene
derivatives containing electron-withdrawing groups afforded
Table 1 Iodoamidation of styrene with CT and I2 in water
Yield (%)
Department of Applied Chemistry, Graduate School of Engineering,
Osaka University, Yamadaoka 2-1, Suita, Osaka 565-0871, Japan.
E-mail: minakata@chem.eng.osaka-u.ac.jp; Fax: +81 6-6879-7402
w Electronic supplementary information (ESI) available: NMR spectra
and X-ray structure analysis. CCDC 778523. For ESI and
crystallographic data in CIF or other electronic format see DOI:
10.1039/c0cc03855e
1a
1b
Entry
Solvent (2 mL)
1
2
3
4
MeCN
n-Hexane
Styrene
H2O
0
0
0
53
52
32
65
0
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 1905–1907 1905

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Table 2 Iodoamidation of aromatic olefins with CT and I2 in aqueous
mediaa
formation of oligomers (entries 4 and 5) and the complete
stereoselectivity of the reaction (entries 6–8) suggest that cyclic
iodonium intermediates are likely involved in the reaction. The
iodoamidation of a-methylstyrene produced the iodoamidated
compound 9 containing a quaternary carbon center (entry 9).
The successful transformation of aromatic olefins into
iodoamidated compounds in an aqueous medium prompted us
to investigate the use of aliphatic olefins as substrates (Table 3).
The simple aliphatic olefin, 1-octene, was subjected to the above
conditions and produced iodoamidated compounds with a
mixture of regioisomers (entry 1). Functional groups such as
ethers, esters and halogens were compatible with this addition
reaction (entries 2–4). Complete stereoselectivity was observed in
the reaction of internal and cyclic olefins (entries 5–7). The
reaction of a cyclic olefin was particularly fast, and prolonging
the reaction time afforded the corresponding aziridine via
cyclization of the iodoamidated compound 16. A conjugated
cyclic olefin, cyclohexadiene, was transformed to compound 17
as a sole product with stereo-, regio-, and chemoselectivity.
Entry
Olefin (equiv.)
Adduct
Yield (%)
73
1
2
3
4
5
6
7
8
85b
84
91c
74b
81b
67c
Table 3 Iodoamidation of aliphatic olefins with CT and I2 in aqueous
mediaa
Entry
Olefin
Adducts
Yield (%)
1
85
99
2
3
4
84
82
73
87b
74b
9
a
Reaction conditions: CT (1 mmol), I2 (0.5 mmol), olefin (0.5–0.85 mmol),
b
c
H2O (2 mL), rt, 1 h. n-Hexane (100 mL) was added. CH2Cl2
(100 mL) was added.
the corresponding adducts 2 and 3 in good yields (entries 2 and
3). The reaction of electron-rich styrene derivatives resulted in
the production of significant amounts of oligomerized
compounds. This situation could be circumvented by the
addition of a small amount of organic solvent to the reaction
mixture (entries 4 and 5). The iodoamidation reaction was
applied to disubstituted aromatic olefins. In these cases, the
use of 1.5–1.7 equivalents of the substrates afforded good yields
(entries 6, 7 and 9). When trans- and cis-b-methylstyrenes were
treated with CT and iodine in water, the corresponding adducts
6 and 7 were obtained with complete stereoselectivity (entries 6
and 7). Although the stereocontrol of addition reactions to
cis-b-methylstyrene is very difficult, it is noteworthy that the
stereoselectivity of the present iodoamidation reactions was
completely controlled. Indene was converted into the trans
iodoamidated product 8 in high yield. The X-ray structure of
the product confirmed that the stereochemistry of the
iodoamidated compound 8 was trans adduct (entry 8).10 The
5
6
7
61b
92b
83c
8
64
a
Reaction conditions: CT (1 mmol), I2 (0.5 mmol), olefin (1 mmol), H2O
b
c
(2 mL), rt, 1 h. CH2Cl2 (100 mL) was added. Reaction time: 2 min.
c
1906 Chem. Commun., 2011, 47, 1905–1907
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Table 4 Iodoamidation of electron-deficient olefins with CT and I2 in
aqueous mediaa
Table 5 One pot iodoamidation from sulfonamide
Entry
1
Olefin (equiv.)
Adduct
Yield (%)
68
Entry
1
Olefin (equiv.)
Adduct
Yield (%)
82
2
3
95
2
97a
73
83b
99c
3
4
a
CH2Cl2 (100 mL) was added.
a
Reaction conditions: CT (1 mmol), I2 (0.5 mmol), olefin (0.5–1 mmol),
b
c
H2O (2 mL), rt, 1 h. CH2Cl2 (100 mL) was added. Et2O (400 mL)
was added.
We gratefully acknowledge the Iodine Utilizations Support
Program in the 2010 fiscal year from the Society of Iodine
Science (SIS).
The method was also found to be applicable to electron-
deficient olefins (Table 4). When methyl vinyl ketone was treated
with CT and iodine in water, the a-iodo-b-amidated ketone 18
was obtained with complete regioselectivity (entry 1). The
reaction of an a,b-unsaturated ester with CT and iodine
proceeded in high yield (entry 2). An a,b-unsaturated amide
was also converted into an iodoamidated compound (entry 3).
The reaction of trans-b-nitrostyrene gave an a-amidated
compound 21, which contained no iodine substituent, by
treatment with aqueous Na2S2O3 as a work-up process11
(entry 4). On the other hand, the reaction of an electron-rich
olefin12 such as butyl vinyl ether gave a complicated mixture.
While the above findings demonstrate that the present
method can be used in reactions with wide range of olefins,
the nitrogen source was restricted to the use of chloramine-T. To
extend the scope of the reaction, the one pot iodoamidation
from a simple amide involving the in situ generation of a
chloramine salt was examined, as shown in Table 5. To
obtain primary amines more readily, the introduction
of trimethylsilylethanesulfonamide was investigated. The
sulfonamide was treated with aqueous NaOH and t-BuOCl to
generate the chloramine salt in situ. The unstable intermediate,
without isolation, was subjected to the present iodoamidation
reaction using three types of olefins, and the desired adducts
22–24 were obtained in good to excellent yields.
Notes and references
1 (a) Well documented review, see: G. Li, S. R. S. S. Kotti and
C. Timmons, Eur. J. Org. Chem., 2007, 2745; (b) Y. Ueno,
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K. Oshima, J. Org. Chem., 2003, 68, 3246; (f) X.-L. Wu and
G.-W. Wang, J. Org. Chem., 2007, 72, 9398.
2 J. E. G. Kemp, in Comprehensive Organic Synthesis, ed. B. M. Trost
and I. Fleming, Pergamon, Oxford, 1991, vol. 7, p. 469.
3 (a) A. Hassner and L. A. Levy, J. Am. Chem. Soc., 1965, 87, 4203;
(b) W. F. Flowler, A. Hassner and L. A. Levy, J. Am. Chem. Soc.,
1967, 89, 2077; (c) Recently, an elegant method for azido iodination
of olefins using TMSN3 was developed by Barluenga’s group. See:
J. Barluenga, M. A-Perez, F. J. Fananas and J. M. Gonzalez, Adv.
´ ´
Synth. Catal., 2001, 343, 335.
4 (a) J. Barluenga, J. M. Gonzalez, J. P. Campos and A. Gregorio,
Angew. Chem., Int. Ed. Engl., 1985, 24, 319; (b) Y. Yeung, S. Hong
and E. J. Corey, J. Am. Chem. Soc., 2006, 128, 9644; (c) Y. Yeung,
S. Hong and E. J. Corey, J. Am. Chem. Soc., 2006, 128, 6310.
5 (a) S. Minakata, Y. Yoneda, Y. Oderaotoshi and M. Komatsu,
Org. Lett., 2006, 8, 967; (b) J. Hayakawa, M. Kuzuhara and
S. Minakata, Org. Biomol. Chem., 2010, 8, 1424.
6 S. Minakata, Acc. Chem. Res., 2009, 42, 1172.
7 (a) S. Minakata and M. Komatsu, Chem. Rev., 2009, 109, 711;
(b) A. Chanda and V. V. Fokin, Chem. Rev., 2009, 109, 725;
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(d) C. I. Herrerıas, X. Yao, Z. Li and C.-J. Li, Chem. Rev., 2007,
107, 2546.
8 (a) T. Ando, D. Kano, S. Minakata, I. Ryu and M. Komatsu,
Tetrahedron, 1998, 54, 13485; (b) D. Kano, S. Minakata and
M. Komatsu, J. Chem. Soc., Perkin Trans. 1, 2001, 3186;
(c) S. Minakata, D. Kano, Y. Oderaotoshi and M. Komatsu,
Angew. Chem., Int. Ed., 2004, 43, 79.
9 (a) M. K. Ghorai, D. Kalpataru, A. Kumar and K. Ghosh,
Tetrahedron Lett., 2005, 46, 4103; (b) G. Sabitha, R. S. Babu,
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10 See the ESIw.
11 P. A. Wade, P. A. Kondeacki and P. J. Carroll, J. Am. Chem. Soc.,
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12 M. D. Castro and C. H. Marzabadi, Tetrahedron Lett., 2004, 45,
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Although the precise mechanism of the reaction is unclear at
present, a proposed mechanism is shown in ESI.w
From the results of the present study, an efficient and
convenient method was developed, which represents a new
and general procedure for the iodoamination of olefins. The
method has a very broad scope in terms of aromatic, aliphatic,
and electron-deficient olefins that can be used, thus allowing
access to a wide range of iodoamidated compounds. Moreover,
the iodo substituent is a versatile functional group that can be
used in further transformations. This reaction proceeds under
extremely mild conditions with high selectivity and efficiency.
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 1905–1907 1907