Iodine-catalyzed intermolecular hydroamination of vinyl arenes

Article abstract of DOI:10.1016/j.tetlet.2009.07.010

The vinyl arenes undergo smooth hydroamination with sulfonamides in the presence of 10 mol % of iodine to furnish tosyl and mesyl-protected secondary amines in excellent yields in short reaction times. The use of inexpensive and readily available molecula

Full text of DOI:10.1016/j.tetlet.2009.07.010

Tetrahedron Letters 50 (2009) 5351–5353
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Iodine-catalyzed intermolecular hydroamination of vinyl arenes
*
J. S. Yadav , B. V. Subba Reddy, T. Srinivasa Rao, B. Bala M. Krishna
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The vinyl arenes undergo smooth hydroamination with sulfonamides in the presence of 10 mol % of
iodine to furnish tosyl and mesyl-protected secondary amines in excellent yields in short reaction times.
The use of inexpensive and readily available molecular iodine makes this method quite simple, more con-
venient, and practical.
Received 22 May 2009
Revised 30 June 2009
Accepted 3 July 2009
Available online 9 July 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Hydroamination
Vinyl arenes
Molecular iodine
Sulfonamides
The intermolecular hydroamination of alkenes is one of the di-
rect and most efficient approaches for the production of amines.1,2
Consequently; there have been some reports on intermolecular
hydroamination of olefins with amides using Ph3PAuOTf,
Cu(OTf)2/BINAP, (COD)Pt(OTf)2, Bi(OTf)3/[Cu(CH3CN)4]PF6, FeCl3,
TfOH, InBr3, silicotungstic acid, and [(PhO)3P]AuCl/AgOTf.3–5
Uncatalyzed hydroamination is prohibited by a large activation en-
ergy barrier under ambient conditions, especially with electroni-
cally neutral alkenes. However, few intermolecular additions of
amines to olefins have been reported with Pd(O2CCF3)2/DPPF/TfOH,
[Rh(COD)(DPEphos)]BF4, and Ph3CB(C6F5)4.6,7 Since amines and
their derivatives have become increasingly useful and important
in the field of drugs and pharmaceuticals, the hydroamination of
alkenes remains an important and challenging strategy.
This result provided the incentive for further study of reactions
with various olefins and sulfonamides. Interestingly, various vinyl
arenes such as p-methyl-, p-t-butyl-, p-chloro-, p-methoxy-, and
a-methylstyrenes underwent smooth hydroamination with p-tolu-
enesulfonamide under identical conditions (Table 1, entries b–k).
The reactions proceeded smoothly by 10 mol % of iodine in refluxing
toluene under neutral conditions to afford the a-amido derivatives
in excellent yields. In case of styrenes, the products were formed
by the selective addition of TsNH2 at benzylic position (Table 1, en-
tries a–k). Furthermore, cyclic olefins such as 1,2-dihydronaphtha-
lene and indene also participated well in this reaction to give the
corresponding 1-amido derivatives in good yields (Table 1, entries
l–o, Scheme 2).
Next, we have investigated the reactions of alkenes with differ-
ent sulfonamides such as benzenesulfonamide, methanesulfonam-
Recently, molecular iodine has received considerable attention
in organic synthesis because of its low cost and ready availability.
The mild Lewis acidity associated with iodine has enhanced its use
in organic synthesis to perform several organic transformations
using stoichiometric levels to catalytic amounts.8
ide, and saccharin (Table 1). Interestingly,
a-methylstyrene also
underwent smooth addition with TsNH2 under similar conditions
(Table 1, entry k). Furthermore, saccharin also underwent smooth
hydroamination with p-methylstyrene to produce the correspond-
ing amido derivative (Table 1, entry e). The yields were generally
high and the reactions went to completion in short times (Table
1, entries a–o). In general, the hydroamination was clean and no
Following our interest in the catalytic uses of molecular iodine,9
we herein report an efficient method for the hydroamination of vi-
nyl arenes with sulfonamides using molecular iodine. Initially, we
attempted an intermolecular hydroamination of a readily available
styrene 1 (3 equiv) with p-toluenesulfonamide 2 (1 equiv) in the
presence of 10 mol % of I2. The reaction proceeded well in toluene
at 110 °C and the desired product,
isolated in 92% yield (Scheme 1).
a-phenylethyl amide (3a) was
NHTs
I2 (10 mol%)
Me
+
TsNH2
Toluene, 110 °C
1
3a
2
* Corresponding author. Tel.: +91 40 27193434; fax: +91 40 27160512.
E-mail address: yadav@iict.res.in (J.S. Yadav).
Scheme 1.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.07.010

5352
J. S. Yadav et al. / Tetrahedron Letters 50 (2009) 5351–5353
Table 1
Table 1 (continued)
Iodine-catalyzed intermolecular hydroamination of vinyl arenes
Entry Alkene
(3 equiv)
Nucleophile
(1 equiv)
Producta
Time Yieldb
Entry Alkene
(3 equiv)
Nucleophile
(1 equiv)
Producta
Time Yieldb
(h)
(%)
(h)
(%)
NHTs
NHTs
l
TsNH2
2.5
86
a
TsNH2
2.0
92
NHSO2Ph
NHTs
NHSO2Ph
m
n
PhSO2NH2
3.0
3.0
3.5
80
84
80
b
PhSO2NH2
2.5
4.0
2.0
90
86
90
TsNH2
NHSO2CH3
c
CH3SO2NH2
TsNH2
O
NHSO2Ph
o
PhSO2NH2
NHTs
d
Me
a
Me
The products were characterized by NMR, IR, and mass spectrometry.
Yield refers to pure products after chromatography.
b
O
NHTs
N
SO2
e
2.0
78
I2 (10 mol %)
NH
SO2
Me
+
TsNH2
°
Toluene, 110 C
Me
3l
Scheme 2.
NHSO2CH3
f
CH3SO2NH2
4.0
2.5
2.5
3.0
78
85
86
80
by-products such as iodo adducts were detected under these
conditions.
Me
Me
The effects of various solvents such as dichloroethane, THF, ace-
tonitrile 1,4-dioxane, and toluene were studied in the hydroamin-
ation of styrene with TsNH2. Low yields (10–50%) were obtained
when styrene was reacted with TsNH2 using 10 mol % of iodine
in dichloroethane, THF, acetonitrile, and 1,4-dioxane. Of these, tol-
uene appeared to give the best results. In the absence of catalyst,
the reactions did not proceed even after long reaction times (10–
24 h). There was no significant improvement in reaction rate and
yields when the reaction was performed using stoichiometric
amounts of iodine. However, long reaction times (36–48 h) are re-
quired when 5 mol % of iodine was used. Therefore, the use of
10 mol % of iodine is ideal to achieve the best conversion. The
use of excess of olefin (3 equiv) was also crucial to obtain high con-
version. This method does not require the use of expensive or cor-
rosive reagents and no precautions need to be taken to exclude
moisture from the reaction medium. The scope and generality of
this process is illustrated with respect to various olefins and sul-
fonamides and the results are presented in Table 1.10 Mechanisti-
cally, iodine may initially react with sulfonamide to furnish a
catalytic amount of HI, which subsequently may react with olefin.
The resulting iodide may undergo a nucleophilic substitution by
the amine to furnish the desired product.
NHTs
g
TsNH2
NHSO2Ph
h
PhSO2NH2
NHTs
i
TsNH2
Cl
Cl
NHSO2Ph
j
PhSO2NH2
1.5
3.0
75
76
MeO
MeO
In summary, we have described a simple and efficient protocol
for the intermolecular hydroamination of vinyl arenes with sulfon-
amides using iodine as the novel reagent under neutral conditions.
The notable features of this procedure are high conversions, short
reaction times, operational simplicity, and ready availability of re-
agents at low cost which make it a useful and attractive strategy
NHTs
k
TsNH2

J. S. Yadav et al. / Tetrahedron Letters 50 (2009) 5351–5353
5353
2005, 46, 5771; (h) Pukan, P. Synth. Commun. 2004, 34, 1065; (i) Chu, C.-M.; Yao,
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for the preparation of
dane, and 1-aminotetrahydronaphthalene derivatives.
a-phenylethyl amine, 1-aminodihydroin-
9. (a) Yadav, J. S.; Reddy, B. V. S.; Hashim, S. R. J. Chem. Soc., Perkin Trans. 1 2000,
3025; (b) Yadav, J. S.; Reddy, B. V. S.; Premalatha, K.; Swam, T. Tetrahedron Lett.
2005, 46, 2687; (c) Yadav, J. S.; Reddy, B. V. S.; Sabitha, G.; Reddy, G. S. K. K.
Synthesis 2000, 1532; (d) Yadav, J. S.; Reddy, B. V. S.; Rao, C. V.; Chand, P. K.;
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10. Experimental procedure: A mixture of olefin (3 mmol), sulfonamide (1 mmol),
and iodine (10 mol %) was stirred in toluene (5 mL) at 110 °C for a specified time
to complete the reaction indicated by TLC (Table 1). After completion of the
reaction, reaction mixture was cooled to room temperature and then washed
with saturated sodium thiosulfate aqueous solution, and the solution was
extracted with ethyl acetate (2 Â 10 mL). The combined organic layers were
dried over anhydrous Na2SO4, concentrated in vacuo, and purified by column
chromatography. The products were characterized by IR, 1H NMR, 13C NMR, and
mass spectrometry.N-[1-(4-Methylphenyl)ethyl]-p-toluenesulfonamide (entry
Acknowledgment
T.S.R. and B.M.K. thank the CSIR, New Delhi, for the award of
fellowships.
References and notes
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3d): Light green solid, mp 114–116 °C, IR (KBr):
m 3252, 2920, 1646, 1513,
1324, 1158, 1083, 958, 810, 666 cmÀ1 1H NMR (300 MHz, CDCl3): d 7.63 (d,
.
J = 7.5 Hz, 2H), 7.18 (d, J = 8.3 Hz, 2H), 6.98 (s, 4H), 5.16 (d, J = 6.8 Hz, 1H), 4.45–
4.36 (m, 1H), 2.43 (s, 3H), 2.30 (s, 3H), 1.43 (d, J = 6.8 Hz, 3H). 13C NMR (75 MHz,
CDCl3): d 20.89, 21.35, 23.39, 53.32, 125.96, 127.01, 128.99, 129.26, 136.89,
137.65, 139.11, 142.85. ESI-MS (m/z): (M+Na): 312. HRMS m/z: calcd for
C16H19NO2NaS
Butyl)phenyl]ethyl]-benzenesulfonamide (entry 3h): IR (neat):
2962, 2868, 1512, 1447, 1323, 1165, 1091, 962, 833, 721 cmÀ1
[M+Na]+:
312.1034,
found,
312.1044.N-[1-[4-(tert-
3276, 3061,
1H NMR
m
.
(200 MHz, CDCl3): d 7.71–7.66 (m, 2H), 7.38–7.23 (m, 3H), 7.11–6.94 (m, 4H),
5.89 (d, J = 7.3 Hz, 1H), 4.51–4.3 (m, 1H), 1.41 (d, J = 7.3 Hz, 3H), 1.24 (s, 9H). 13C
NMR (75 MHz, CDCl3):d23.3, 31.15, 34.24, 53.38, 125.15, 125.73, 126.92, 128.55,
131.96, 138.69, 140.68, 150.05. ESI-MS: m/z: (M+Na): 340. HRMS m/z: calcd for
C18H23NO2NaS [M+Na]+: 340.1347, found, 340.1351.N-(2,3-Dihydro-1H-1-
indenyl)-p-toluenesulfonamide (entry 3n): White solid, mp 139–141 °C, IR
(KBr):
m
3261, 3064, 2924, 2854, 1596, 1457, 1422, 1317, 1159, 1092, 917,
.
668 cmÀ1
1H NMR (200 MHz, CDCl3): d 7.87 (d, J = 8.0 Hz, 2H), 7.39–7.13 (m, 6H),
8. (a) Togo, H.; Iida, S. Synlett 2006, 2159; (b) Lin, X.-F.; Cui, S.-L.; Wang, Y. G.
Tetrahedron Lett. 2006, 47, 4509; (c) Chen, W.-Y.; Lu, J. Synlett 2005, 1337; (d)
Royer, L.; De, S. K.; Gibbs, R. A. Tetrahedron Lett. 2005, 46, 4595; (e) Banik, B. K.;
Fernandez, M.; Alvarez, C. Tetrahedron Lett. 2005, 46, 2479; (f) Wang, S.-Y.
Synlett 2004, 2642; (g) Ko, S.; Sastry, M. N. V.; Lin, C.; Yao, C.-F. Tetrahedron Lett.
4.89–4.69 (m, 2H), 3.03–2.7 (m, 2H), 2.52 (s, 3H), 2.44–2.30 (m, 1H), 1.90–1.71
(m, 1H). 13C NMR (75 MHz, CDCl3): d 21.49, 29.90, 34.59, 58.67, 124.04, 124.74,
126.78, 127.10, 128.21, 129.72, 138.21, 141.96, 142.78, 143.36. ESI-MS (m/z):
(M+Na): 310. HRMS m/z: calcd for C16H17NO2NaS [M+Na]+: 310.0877, found,
310.0881.