(Triphenyl phosphite)gold(I)-catalyzed intermolecular hydroamination of alkenes and 1,3-dienes

Article abstract of DOI:10.1021/ol801104w

(Chemical Equation Presented) Intermolecular addition of different sulfonamides to alkenes and conjugated dienes can be carried out using a low loading of (triphenyl phosphite)gold(I) chloride and silver triflate as a catalytic mixture. The reaction can be performed under conventional thermal or microwave conditions and at rt in the case of dienes. Terminal alkenes undergo regioselective hydroamination at the internal carbon atom and dienes at the less substituted double bond.

Full text of DOI:10.1021/ol801104w

ORGANIC
LETTERS
2008
Vol. 10, No. 14
2919-2922
(Triphenyl phosphite)gold(I)-Catalyzed
Intermolecular Hydroamination of
Alkenes and 1,3-Dienes†
Xavier Giner and Carmen Na´jera*
Departamento de Qu´ımica Orga´nica and Instituto de S´ıntesis Orga´nica (ISO),
Facultad de Ciencias, UniVersidad de Alicante, Apartado 99, E-03080 Alicante, Spain
cnajera@ua.es
Received March 11, 2008
ABSTRACT
Intermolecular addition of different sulfonamides to alkenes and conjugated dienes can be carried out using a low loading of (triphenyl
phosphite)gold(I) chloride and silver triflate as a catalytic mixture. The reaction can be performed under conventional thermal or microwave
conditions and at rt in the case of dienes. Terminal alkenes undergo regioselective hydroamination at the internal carbon atom and dienes at
the less substituted double bond.
Acid- and metal-promoted hydroamination of alkenes (AHA)
is a general and atom-economical method for the synthesis
of amines or derivatives.1 Intramolecular hydroaminations
are faster and more general than intermolecular processes.
In the last case, the regioselectivity is difficult to control,
not only for alkenes but also for 1,3-dienes, which can afford
1,2- and 1,4-addition products. Recently, TfOH,2 (Ph3P)AuCl/
AgOTf,3 [PtCl2(CH2dCH2]2,4 Cu(OTf)2/dppe,5 and Bi(OTf)3/
as efficient catalyst, although regioisomeric mixtures and
hydrovinylation products due to cationic intermediates are
formed.2 Therefore, a more efficient catalyst should be
developed for the hydroamination of alkenes and dienes.
We envisaged that the use of stronger electron-withdraw-
ing ligands would increase the interaction of the LAu+ with
the C-C double bond and consequently a greater catalytic
activity. Here, we report that the simple (triphenyl phosphi-
te)gold(I) chloride8/AgOTf can be used as a very efficient
6
[Cu(CH3CN)4]PF6 have been reported as catalysts for the
addition of sulfonamides to alkenes2,3a,c,4 and to 1,3-
dienes.2,3b,5,6 The gold(I)7 complex (Ph3P)AuCl/AgOTf has
been used for the intermolecular hydroamination of alkenes
and dienes.3 However, metal-catalyzed intermolecular AHA
required high loadings, generally 5-10 mol %. In the
presence of triflic acid, a low loading (1 mol %) can be used
(3) (a) Zhang, J.; Yang, C.-G.; He, C. J. Am. Chem. Soc. 2006, 128,
1798–1799. (b) Brouwer, C.; He, C. Angew. Chem., Int. Ed. 2006, 45, 1744–
1747. (c) Liu, X.-Y.; Li, C.-H.; Che, C.-M. Org. Lett. 2006, 8, 2707–2710.
(4) Liu, C.; Bender, C. F.; Han, X.; Widenhoefer, R. A. Chem. Commun.
2007, 3607–3618.
(5) Taylor, J. G.; Whittall, N.; Hii, K. K. Org. Lett. 2006, 8, 3561–
3564.
† Dedicated to Professor E. J. Corey on occasion of his 80th birthday.
(1) Recent reviews: (a) Hultzsch, K. C. AdV. Synth. Catal. 2005, 347,
367–391. (b) Hultzsch, K. C. Org. Biomol. Chem 2005, 3, 1819–1824. (c)
Roesky, P. W.; Mu¨ller, T. E. Angew. Chem. Int. Ed. 2003, 42, 2708–2710.
(d) Mu¨ller, T. E.; Beller, M. Chem. ReV. 1998, 98, 675–704.
(2) (a) Li, Z.; Zhang, J.; Brouwer, C; Yang, C.-G.; Reich, N. W.; He,
C. Org. Lett. 2006, 8, 4175–4178. (b) Rosenfeld, D. C.; Shekhar, S;
Takemiya, A.; Utsunomiya, M.; Hartwig, J. F. Org. Lett. 2006, 8, 4179–
4182.
(6) Quin, H.; Yamagiwa, N.; Matsunaga, S.; Shibasaki, M. J. Am. Chem.
Soc. 2006, 128, 1611–1614.
(7) For recent reviews about gold catalysis, see: (a) Hashmi, A. S. K.
Chem. ReV. 2007, 107, 3180–3211. (b) Fu¨rstner, A.; Davies, P. W. Angew.
Chem., Int. Ed. 2007, 46, 3410–3449. (c) Hashmi, A. S. K.; Hutchings,
G. J. Angew. Chem., Int. Ed. 2006, 45, 7896–7936.
(8) Hitchcock, P. B.; Pye, P. L. J. Chem. Soc., Dalton Trans. 1977,
1457–1460.
10.1021/ol801104w CCC: $40.75
Published on Web 06/14/2008
2008 American Chemical Society

and general catalyst for the addition of sulfonamides to
alkenes and dienes.
gave a very low conversion (Table 1, compare entries 7 and
10).
Preliminary studies about the catalytic activity of different
gold(I) chloride complexes and AgOTf were screened for
the addition of p-toluenesulfonamide (TsNH2, 2a) to nor-
bornene (1a) in toluene under microwave heating (Table 1).
The performance of [(PhO)3P]AuCl/AgOTf as catalyst
under the optimized reaction conditions was subsequently
examined with norbornene (1a) and cyclohexa-1,3-diene (1f)
using different nucleophiles (Table 2). Thus, hydroamination
Table 1. Catalysts Studies for the Addition of TsNH2 to
Table 2. Hydroamination of Norbornene and
Norbornenea
Cyclohexa-1,3-diene with Different Sulfonamides Catalyzed by
a
[(PhO)3P]AuCl/AgOTf
cat.
(mol %)
time
entry
T (°C) (min) convnb qa(%)
1
2
3
4
5
6
7
8
9
(Me2S)AuCl/AgOTf (5)
(Ph3P)AuCl/AgOTf (5)
90
85
90
85
85
90
90
90
90
90
30 96
15 99 (92)
30 58
15 99
15 99
30 99
30 99
30 94 (90)
30 60
(Ph3P)AuCl/AgOTf (0.1)
[(BTFP)3P]AuCl/AgOTf (5)
[(PhO)3P]AuCl/AgOTf (5)
[(PhO)3P]AuCl/AgOTf (1)
[(PhO)3P]AuCl/AgOTf (0.1)
[(PhO)3P]AuCl/AgOTf (0.05)
[(PhO)3P]AuCl/AgOTf (0.01)
cat.
entry mol %
convnb
(%)
sulfonamide
TsNH2
4-MeOC6H4SO2NH2 PhMe
4-NO2C6H4SO2NH2 PhMe
MeSO2NH2
TsNH2
solvent
PhMe
no.
1
2
3
4
5
6
7
0.05
0.1
5
5
1
3aa 94 (90)
3ab 99 (96c)
10 HOTf (0.1)
30
8
3ac
0
a Reactions were performed with TsNH2 (171 mg, 1 mmol), norbornene
(376 mg, 4 mmol), and catalyst (see column) in dry toluene (2 mL) under
Ar in a microwave reactor (70 W, 10 psi) with air stream cooling.
b Determined by GC, based on TsNH2. The isolated yield after flash
chromatography is shown in parentheses.
dioxane 3ad 98 (65)
PhMe 3fa 66
4-MeOC6H4SO2NH2 dioxane 3fb - (77)
MeSO2NH2 dioxane 3fd 85 (65)
1
5
a Reactions were performed with sulfonamide (1 mmol), diene (4 mmol),
catalyst (see column) in dry solvent (2 mL) under Ar in a microwave reactor
(70 W, 10 psi) with air stream cooling. b Determined by GC, based on
sulfonamide. In parenthesis isolated yield after flash chromatography. c After
recrystallization from hexane/EtOAc.
In the presence of the commonly used (Me2S)AuCl/AgOTf
and (Ph3P)AuCl/AgOTf, the reaction took place in 30 and
15 min, respectively, affording exo-3aa in high yields, using
5 mol % loading (Table 1, entry 1 and 2). However, when
the loading of the last catalyst was lowered to 0.1 mol %,
only 58% conversion was observed at 90 °C after 30 min
irradiation (Table 1, entry 3). The mixture of the gold(I)
chloride complex formed with the strong electron-withdraw-
of norbornene with electron-rich 4-methyl- and 4-methoxy-
benzenesulfonamide gave rise to full conversion (Table 2,
entries 1 and 2), whereas in the case of 4-nitrobenzene-
sulfonamide the reaction failed (Table 2, entry 3). The
addition of methanesulfonamide was performed in dioxane
due to solubility problems in toluene, affording product 3ad
in good yield (Table 2, entry 4). The hydroamination of
cyclohexa-1,3-diene (1f) was performed with electron-rich
4-methyl- and 4-methoxybenzenesulfonamide with 1 mol %
loading of catalysts affording products 3fa and 3fb, respec-
tively, in good yields (Table 2, entries 5 and 6). In the case
of methanesulfonamide, a 5 mol % loading of catalysts in
dioxane was used, giving product 3fd in good yield (Table
2, entry 7).
The study about the scope of this hydroamination reaction
was carried out with different alkenes and dienes and TsNH2
(1a) as nucleophile using [(PhO)3P]AuCl/AgOTf as catalyst
(Table 3). Norbornene gave product 3aa with full conversion
working also under thermal (14 h) or microwave (MW) (30
min) conditions with 0.05 mol % loading of catalyst (Table
3, entries 1 and 2). The same reaction catalyzed by
(Ph3P)AuCl/AgOTf needed a 5 mol % loading.3a In the case
of cyclohexene and cyclooctene, the corresponding products
ing
tris[3,5-bis(trifluoromethyl)phenyl]phosphine
[(BTFP)3P]9 and AgOTf provided full conversion under the
same reaction conditions (Table 1, compare entries 2 and
4).
Then, the gold(I) complex [(PhO)3P]AuCl8,10,11 derived
from the inexpensive ligand triphenyl phosphite, which
shows strong electron-withdrawing ability and is also an
strong π-acceptor phosphorus ligand, was assayed. A 1:1
mixture of this complex and AgOTf11 gave excellent
conversions under different loadings, such as 5, 1, 0.1, and
0.05 mol % (Table 1, entries 5-8). However, when the
amount of catalyst was decreased to 0.01 mol %, only 60%
conversion was observed (Table 1, entry 9). For comparison,
using TfOH (0.1 mol %) under the same reaction conditions
(9) Nunokawa, K.; Onaka, S.; Tatematsu, T.; Ito, M.; Sakai, J. Inorg.
Chim. Acta 2001, 322, 56–64.
(10) [(PhO)3P]AuCl/AgSbF6 has been recently used as catalyst for the
intramolecular hydroarylation of allenes: (a) Tarselli, M. A.; Gagne´, M. R.
J. Org. Chem. 2008, 73, 2439–2441
.
(11) Kowala, C.; Swan, J. M. Aust. J. Chem. 1966, 19, 547–554
.
2920
Org. Lett., Vol. 10, No. 14, 2008

a
Table 3. Hydroamination of Akenes and Dienes with TsNH2 Catalyzed by [(PhO)3P]AuCl/AgOTf
a Reactions were performed with TsNH2 (171 mg, 1 mmol), alkene or diene (4 mmol), and [(PhO)3P]AuCl/AgOTf (see column) in dry solvent (2 mL)
under normal or MW heating and Ar atmosphere. b Determined by GC based on TsNH2. The isolated yield after flash chromatography is shown in parentheses.
c Relative ratio determined by 1H NMR over the crude reaction mixture. d Under microwave heating (70 W, 10 psi) with air stream cooling. e A 10/1 mixture
(determined by NMR) of compound 3ea and the regioisomer N-[1-(4-methoxyphenyl)propyl]-4-toluenesulfonamide was obtained. f The reaction was performed
with HOTf. g A 4/1 mixture (determined by NMR) of compound 3ea and the regioisomer N-[1-(4-methoxyphenyl)propyl]-4-toluenesulfonamide was obtained.
h Z/E: 1/1.8. i Z/E: 1/2.5.
3ba and 3ca could only be obtained in good yields using
conventional heating (85 °C) and a higher catalyst loading
(Table 3, entries 3 and 4). When using styrene, the addition
took place regioselectively, giving product 3da in better yield
under MW than under conventional heating (Table 3, entries
5 and 6). Regioselective addition to 1-allyl-4-methoxyben-
zene (1e) was also observed affording a 10/1 mixture of
product 3ea and N-[1-(4-methoxyphenyl) propyl]-4-toluene-
sulfonamide in good yields under both type of heating (Table
3, entries 7 and 8). The triflic acid catalyzed hydroamination
of 1e gave a 4/1 mixture of regioisomers in 75% isolated
yield (Table 3, compare entries 8 and 9).
Conjugated dienes showed a higher reactivity than simple
alkenes, the reaction being performed also at rt in CH2Cl2
as solvent. Thus, cyclohexa-1,3-diene gave product 3fa in
moderate yields under heating with only 0.1 mol % of gold(I)
catalyst. However, at rt, the corresponding product was
obtained in 90% yield after 1 d at rt with 1 mol % loading
of catalyst (Table 3, entries 10-12). In the case of penta-
1,3-diene (1g), which was purchased as a Z/E 1/1.8 diaster-
omer mixture, reacted with TsNH2 in good yields providing
regioselectively product 3ga as mixture of diasteromers in a
different ratio than the starting diene 1g (Table 3, entries
13-15). Similar results were obtained with 3-methylpenta-
1,3-diene (1h, Z/E: 1/2.5), which provided product 3ha
predominatly as E-diastereomers (Table 3, entries 16, 18,
and 20). The highest E/Z ratio for acyclic dienes resulted at
rt, products 3ga and 3ha being obtained in 16/1 and 49/1
ratios, respectively. Product 3ha has been prepared previ-
ously using 5-fold of (Ph3P)AuCl/AgOTf (5 mol %).3b
When the same reactions were performed using HOTf as
catalyst, lower conversions were obtained under thermal
conditions and similar results at rt (Table 3, entries 17, 19,
and 21). The isomerization of the trisubstituted double bond
was studied by NMR in the presence of the gold catalyst
and in a paralell experiment with HOTf. After 1 h in CDCl3,
diene 1h gave a 1/1 and 2/98 E/Z mixture with gold and
HOTf, respectively. This means that the gold(I) complex was
able to isomerize the double C-C bond. The presence of
HOTf in the solution of [(PhO)3P]AuCl/AgOTf in CDCl3
was not detected by 19F NMR.
The formation of [(PhO)3P]Au+(CH3CN) (m/z ) 548) by
reaction of [(PhO)3P]AuCl and AgOTf in acetonitrile, was
detected by ESI-MS. As has been proposed from calcula-
tions,12 the interaction between the [(PhO)3P]Au+ cation and
the TfO- anion is very weak, which would therefore facilitate
Org. Lett., Vol. 10, No. 14, 2008
2921

its substitution by the corresponding alkene or diene. From
31P NMR studies it was observed that the 31P signal of
[(PhO)3P]AuCl at δ 109.93 was moved upfield at δ 95.11
in the case of the possible formation of [(PhO)3P]AuOTf
due to the higher ionic character of the last complex. When
the Z/E mixture of 3-methylpenta-1,3-diene (1h) was added
to the CDCl3 solution of [(PhO)3P]AuOTf, the signal was
moved downfield to δ 104.92, indicating the coordination
of the diene to gold(I). In the case of the 13C NMR studies
of the supposed complex between the diene 1h and gold(I),
the signal intensity in the starting diene of the terminal CH2
at δ 110.02 (E) and 112.97 (Z) diminished. This was probably
due to the coordination of the terminal C-C double bond to
gold(I). This coordination has been recently proposed by DFT
calculations for the hydroamination reaction of 1h with
CbzNH2.12
Scheme 1
.
Proposed Reaction Mechanism for the
Hydroamination of Diene 1h
A plausible mechanism for the hydroamination of 1,3-
dienes, which is in accordance with the proposal by Ujaque
et al.,12 is depicted in Scheme 1. After coordination of the
diene to gold(I), the attack of the sulfonamide would give
intermediates A and B. The regioselective nucleophile attack
to the most coordinated double bond would give intermediate
A, which can be in tautomeric equilibrium with B assisted
by the triflate anion, as proposed by calculations for the
benzyl carbamate addition.12 When aniline, a nucleophile
enable to participate in this tautomeric equilibrium, was
allowed to react with 1h under MW heating or at rt, the
reaction failed. A direct proton transfer from N to the C atom
has a high energy barrier according to these theoretical
studies. After proton transfer to the C atom, intermediate C
would be formed, and final decoordination would provide
the product and regenerate the catalyst.
In conclusion, the studies described above demonstrate that
[(PhO)3P]AuCl/AgOTf is a more efficient catalyst than HOTf
or (Ph3P)AuCl/AgOTf for the intermolecular regioselective
hydroamination of alkenes and dienes with different types
of sulfonamides. The process can be performed with low
catalyst loading in toluene as solvent either under conven-
tional thermal conditions or under MW heating, in shorter
reaction times, except for some cyclic alkenes. In addition,
the reaction can also be performed at rt for 1,3-dienes.
Acknowledgment. This work was financially supported
by the Direccio´n General de Investigacio´n of the Ministerio
de Educacio´n y Ciencia of Spain (Grants CTQ2004-00808/
BQU, CTQ2007-62771/BQU, and Consolider INGENIO
2010 CSD2007-00006), the Generalitat Valenciana (GV05/
157), and the University of Alicante. X.G. thanks the EU,
Project MCPF-Heterocycles/MERG-CT-2007-045626, for a
predoctoral fellowship.
Supporting Information Available: . Experimental pro-
cedure and characterization data for products. This material
is available free of charge via the Internet at http://pubs.acs.org.
(12) Kova´cs, G.; Ujaque, G.; Lledo´s; os, A J. Am. Chem. Soc. 2008,
130, 853–864.
OL801104W
2922
Org. Lett., Vol. 10, No. 14, 2008