Silver-catalyzed intermolecular hydroamination of alkenes and 1,3-dienes

Article abstract of DOI:10.1055/s-0029-1218297

Silver triflate is used as efficient catalyst for the intermolecular addition of 4-toluenesulfonamide to alkenes under thermal or microwave heating. The hydroamination of 1,3-dienes can be performed at 85 °C with low catalyst loading (0.1-5 mol%) or at room temperature using 1 mol% of AgOTf, the use of HOTf affording similar results.

Full text of DOI:10.1055/s-0029-1218297

LETTER
3211
Silver-Catalyzed Intermolecular Hydroamination of Alkenes and 1,3-Dienes
Intermolecular
Hy
a
droaminatio
v
n of Alkene
i
s
and
1
e
,3-Dienes r Giner, Carmen Nájera*
Departamento de Química Orgánica, Facultad de Ciencias and Instituto de Síntesis Orgánica (ISO), Universidad de Alicante,
Apdo. 99, 03080 Alicante, Spain
Fax +34(96)5903549; E-mail: cnajera@ua.es
Received 23 July 2009
rafluoroborate and perclorate gave product 2a in only 5%
Abstract: Silver triflate is used as efficient catalyst for the intermo-
and 22% yield, respectively (Table 1, entries 5 and 6).
lecular addition of 4-toluenesulfonamide to alkenes under thermal
However, silver triflate and hexafluoroantimoniate be-
have similarly giving rise to high yields (Table 1, entries
or microwave heating. The hydroamination of 1,3-dienes can be
performed at 85 °C with low catalyst loading (0.1–5 mol%) or at
room temperature using 1 mol% of AgOTf, the use of HOTf afford- 7 and 8). Silver triflate afforded higher yield (82%) than
ing similar results.
hexafluoroantimoniate (62%) when lowering the catalyst
loading to 0.05 mol% (Table 1, entries 9 and 10). Under
the same conditions, the use of triflic acid (0.05 mol%)
gave only 18% yield in this hydroamination. In the pres-
ence of triphenylphosphane and silver triflate (1 mol%)
the reaction failed (Table 1, entry 11). On the other hand,
a 88% yield was obtained by using triphenylphosphite as
additive (Table 1, entry 12).
Key words: alkenes, conjugated dienes, hydroamination, sulfon-
amides, silver catalysts
Inter- and intramolecular hydroamination reactions of
alkenes, allenes, and alkynes have been extensively used
for the synthesis of acyclic and heterocyclic amines, re-
spectively.1 Alkenes showed a much lower reactivity spe-
cially in the case of intermolecular hydroamination
processes. Recent advances in this field showed that
Brønsted2 and Lewis3 acids, mainly metal complexes,
have been employed to promote this reaction. Electro-
philic gold(I) complexes have shown high efficiency for
the intermolecular hydroamination of alkenes and 1,3-
dienes with carbamates and sulfonamides.4 The active cat-
alyst is prepared in situ by reaction of phosphanes or phos-
phites, gold(I) chloride complexes and a silver salt,
mainly AgOTf, in order to generate cationic gold(I) com-
plexes. Intramolecular hydroamination of alkynes from in
situ generated imines to give pyrroles,5 oximes to give iso-
quinolinones,6 and from primary amines affording
pyrrolines7 have been performed using silver salts. How-
ever, the electrophilic AgOTf has not been used as cata-
lyst in the hydroamination of alkenes. The attempting
addition of benzyl carbamate to dienes such as 3-methyl-
1,3-pentadiene failed.4b In spite of this unsuccessful pre-
cedents, and related to our studies on gold(I)-catalyzed
hydroamination reactions of alkenes and 1,3-dienes, we
carried out control experiments to study if silver salts can
be used as catalysts. Herein, we report the first silver-
catalyzed hydroamination of alkenes and 1,3-dienes with
sulfonamides.
Table 1 Hydroamination of Norbornene with 4-Toluenesulfon-
amidea
AgX
+ TsNH2
NHTs
PhMe, 90 °C (MW)
30 min
1a
2a
Entry
1
Cat. (mol%)
Yield (%)b
AgCl (1)
0
0
2
AgNO3 (1)
3
AgOAc (1)
0
4
AgF (1)
0
5
AgBF4 (1)
5
6
AgClO4 (1)
22
98
99
82
62
0
7
AgOTf (1)
8
AgSbF6 (1)
9
AgOTf (0.05)
AgSbF6 (0.05)
Ph3P (1)/AgOTf (1)
[(PhO)3P](1)/AgOTf (1)
10
11
12
Hydroamination of norbornene (1a) with 4-toluene-
sulfonamide was performed in toluene at 90 °C under mi-
crowave heating during 15 minutes using 1 mol% loading
of different silver salts (Table 1). No reaction was ob-
served when silver chloride, nitrate, acetate, and fluoride
were used as catalysts (Table 1, entries 1–4). Silver tet-
88
a Reactions were performed with TsNH2 (171 mg, 1 mmol), nor-
bornene (376 mg, 4 mmol), AgX (see column) in dry toluene (2 mL)
under Ar in a microwave reactor (70 W, 0.69 bar) with air stream
cooling.
b Isolated crude yield determined by GLC, based on TsNH2.
SYNLETT 2009, No. 19, pp 3211–3213
Advanced online publication: 15.10.2009
DOI: 10.1055/s-0029-1218297; Art ID: G24209ST
© Georg Thieme Verlag Stuttgart · New York
x
x
.x
x
.2
0
0
9
Different alkenes and 1,3-dienes were hydroaminated
with 4-toluenesulfonamide and AgOTf as catalyst and
were compared with HOTf (Table 2).8 Norbornene af-

3212
X. Giner, C. Nájera
LETTER
forded product 2a in 96% yield under conventional heat- (Table 2, entry 7). However, using 5 mol% of HOTf,
ing at 85 °C during 4 hours using 0.5 mol% of AgOTf crude product 2c was obtained in 66% yield impurified by
(Table 2, entry 1). Alternatively, this hydroamination can secondary products from a-pinene isomerization and
be performed at room temperature using CH2Cl2 as sol- dimerization (Table 2, entry 8). Styrene (1d) was regio-
vent and 5 mol% of AgOTf affording 2a in 97% yield selectively transformed into sulfonamide 2d using 5
(Table 2, entry 2). This process has been also described mol% of AgOTf either under conventional or microwave
using 1 mol% of HOTf in 1,2-dichloroethane, yielding 2a heating in toluene at 85 °C in 64% or 58% yield, respec-
in 91% yield (Table 2, entry 3).2d In the case of cyclohex- tively (Table 2, entries 9 and 11), a slight better 70% yield
ene (1b) the addition took place in toluene at 85 °C in low being described using HOTf at 85 °C2c (Table 2, entry 10).
yield (38%) using 2 mol% of AgOTf (Table 2, entry 4), Attempted hydroamination of other terminal alkenes
whereas a higher 58% yield has been obtained using 1 which can be hydroaminated by Au(I)4g failed when using
mol% HOTf2d (Table 2, entry 5). However, when this AgOTf. In general, the use of AgOTf gave cleaner trans-
reaction was performed using solvent-free conditions at formations than HOTf, which in our hands afforded mix-
90 °C under MW heating a higher 71% yield of product tures of alkenes dimeric products.
2b was obtained (Table 2, entry 6). In the case of a-pinene
Conjugated dienes showed a higher reactivity than al-
kenes, the addition of 4-toluenesulfonamide being carried
out under heating and at room temperature. In the case of
cyclohexa-1,3-diene (1e), N-tosylcyclohex-2-enylamine
(1c), the hydroamination took place only without solvent
with concomitant rearrangement to provide N-tosyl-
isobornylamine (2c), structure being confirmed by X-ray
analysis (Figure 1), using 5 mol% of AgOTf in 79% yield
(2e) was obtained in 76% or 49% yield using 0.1 mol% or
Table 2 Hydroamination of Alkenes and Dienes with 4-Toluenesulfonamide Catalyzed by AgOTf or HOTfa
Entry Alkene or diene
Compd
Solvent
Cat. (mol%)
Temp (°C) Time (h) Productb
Compd Yield (%)c
1
2
3
1a
1a
1a
PhMe
CH2Cl2
DCE
AgOTf (0.5)
AgOTf (5)
HOTf (1)
85
25
25
4
24
6
2a
2a
2a
96 (99)
97 (99)
91d
NHTs
NHTs
4
5
6
1b
1b
1b
PhMe
PhMe
neat
AgOTf (2)
HOTf (1)
AgOTf (5)
85
14
22
0.5
2b
2b
2b
38 (50)
58d
71 (88)
85
90e
7
8
1c
1c
neat
neat
AgOTf (5)
HOTf (1)
85
85
14
14
2c
2c
79 (98)
(66)
NHTs
NHTs
9
10
11
1d
1d
1d
PhMe
PhMe
PhMe
AgOTf (5)
HOTf (5)
AgOTf (5)
85
14
14
0.5
2d
2d
2d
64 (72)
70f
58 (76)
85
90e
12
13
14
1e
1e
1e
PhMe
DCE
CH2Cl2
AgOTf (0.1)
HOTf (1)
AgOTf (1)
85
50
25
14
25
24
2e
2e
2e
76 (87)
63d
49 (58)
NHTs
NHTs
15
16
17
1fg
1fg
1fg
PhMe
CH2Cl2
CH2Cl2
AgOTf (0.1)
AgOTf (1)
HOTf (1)
85
25
25
14
24
24
2fh
2fi
2fi
73 (88)
53 (66)
55
18
19
20
1gj
1gj
1gj
PhMe
CH2Cl2
CH2Cl2
AgOTf (0.1)
AgOTf (1)
HOTf (1)
85
25
25
14
24
24
2gk
2gl
2gl
78 (95)
51 (69)
59
NHTs
a Reactions were performed with TsNH2 (171 mg, 1 mmol), alkene or diene (4 mmol), AgOTf (see column) in dry solvent (2 mL) under Ar.
b All products have been identified by 1H and 13C NMR and compare with the previously described in ref. 4g. The new product 2c has been
characterized also by X-ray diffraction analysis (Figure 1).9 All isolated purified products were >95% pure by GLC and/or 1H NMR.
c Isolated yield after flash chromatography or recrystallization. In parentheses, isolated crude yields determined by GLC, based on TsNH2.
d Ref. 2d.
e In a microwave reactor (70 W, 0.69 bar) with air stream cooling.
f Ref. 2c.
g Z/E = 1:1.8.
h Z/E = 1:4.3.
i Z/E = 1:26.
j Z/E = 1:2.5.
k Z/E = 1:8.
l Z/E = 1:99.
Synlett 2009, No. 19, 3211–3213 © Thieme Stuttgart · New York

LETTER
Intermolecular Hydroamination of Alkenes and 1,3-Dienes
3213
Han, X. Eur. J. Org. Chem. 2006, 4555. (f) Hazari, N.;
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Figure 1 Crystal structure of 2c9
1 mol% catalyst loading either in toluene at 85 °C or at
room temperature in CH2Cl2, respectively (Table 2, en-
tries 12 and 14). When HOTf (1 mol%) was employed at
50 °C in 1,2-dichloroethane as solvent, product 2e was ob-
tained in 63% yield2d (Table 2, entry 13). Penta-1,3-diene
(1f) was used as a mixture Z/E (1:1.8), affording product
2f as a Z/E mixture of 1:4.3 at 85 °C and 1:26 at room tem-
perature (Table 2, entries 15 and 16). Similar results have
been observed when HOTf (1 mol%) was used as catalyst
at room temperature, giving product 2f in 55% yield as a
1:26 Z/E mixture (Table 2, compare entries 16 and 17). In
the case of 3-methylpenta-1,3-diene (1g), which was pur-
chased as a 1:2.5 Z/E mixture, product 2g was obtained as
a 1/8 Z/E mixture when the hydroamination was carried
out in toluene at 85 °C in 78% yield (Table 2, entry 18),
whereas >99% of the E-diasteromer 2g was isolated at
room temperature in 51% yield (Table 2, entry 19). Using
HOTf as catalysts at room temperature, a similar 59%
yield of (E)-2g was isolated (Table 2, compare entries 19
and 20).
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J. Org. Chem. 2006, 71, 4525.
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Helquist, P. Org. Lett. 2008, 10, 3903.
In summary, it has been shown that AgOTf is a good cat-
alysts to perform the hydroamination of alkenes and
dienes with 4-toluenesulfonamide, affording similar re-
sults than when using HOTf. This methodology competes
with the gold(I) complexes–silver triflate combination
used for the intermolecular hydroamination of the same
substrates with sulfonamides with the only exception of
terminal alkenes.
(8) General Procedure for the Hydroamination of Alkenes
and Dienes
To a mixture of silver salt (see Tables 1 and 2) and
sulfonamide (171 mg, 1 mmol) in dry solvent (2 mL, see
Tables 1 and 2) was added the alkene or 1,3-diene (4 mmol)
with magnetic stirring in a sealed tube under argon
atmosphere in the dark. For neat experiments (see Table 2,
entries 6–8) no solvent was added. After the corresponding
reaction time under the conditions indicated in Tables 1
and 2 (for microwave heating the vessel was sealed with a
pressure lock, and the mixture was heated at 90 °C in a CEM
Discover MW reactor at 70 W, 0.69 bar with air stream
cooling during 30 min), to the reaction mixture cooled at r.t.
was added H2O (2 mL) and brine (2 drops). The organic
layer was separated, and the aqueous phase was extracted
with EtOAc (2 × 10 mL). All organic phases were mixed,
dried with MgSO4, and evaporated. Pure products were
obtained by recrystallization or by flash chromatography.
(9) Crystallographic data (excluding structure factors) have
been deposited with the Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk./data_request/cif as
supplementary publication no. CCDC 748465 [unit cell
parameters: a 12.2371 (16), b 17.627 (2), c 7.9272 (11),
b 105.117 (3), space group P21/c].
Acknowledgment
This work was financially supported by the Dirección General de
Investigación of the Ministerio de Educación y Ciencia (MEC) of
Spain (Grants, CTQ2007-62771/BQU and Consolider INGENIO
2010, CSD200700006), from the Generalitat Valenciana (Project
PROMETEO/2009/039), and the University of Alicante.
References and Notes
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Foubelo, F.; Tada, M. Chem. Rev. 2008, 108, 3795.
(b) Wolfe, J. P. Synlett 2008, 2913. (c) Shen, H. C.
Tetrahedron 2008, 64, 3885. (d) Severin, R.; Doye, S.
Chem. Soc. Rev. 2007, 36, 1407. (e) Widenhoefer, R. A.;
Synlett 2009, No. 19, 3211–3213 © Thieme Stuttgart · New York