(PPh3)AuCl/AgOTf-catalyzed intermolecular hydroamination of alkynes with sulfonamides to form N-sulfonyl imines

Article abstract of DOI:10.1055/s-0029-1219384

In the presence of a catalytic amount of (PPh₃)AuCl and AgOTf, intermolecular hydroamination of unactivated alkynes with sulfonamides has been shown to proceed and give N-sulfonyl ketimines in medium to excellent yields.

Full text of DOI:10.1055/s-0029-1219384

LETTER
809
(PPh3)AuCl/AgOTf-Catalyzed Intermolecular Hydroamination of Alkynes
with Sulfonamides To Form N-Sulfonyl Imines
Synthesis of
N
-
Sul
o
fonyl Iminesng-Mei Cui,*a Jin-Zhou Zheng,a Liu-Yang Yang,a Chen Zhangb
a
College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, P. R. of China
Fax +86(571)88320320; E-mail: cuidongmei@zjut.edu.cn
b
School of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, P. R. of China
Received 9 October 2009
alkynes to full conversion (entry 3). Decreasing the
amount of AgOTf resulted in lower yields (entries 4 and
5). Using either gold or silver precatalyst alone gave lower
yields (entries 6 and 7). These results indicated that both
Au source and AgOTf played a crucial role in this hy-
droamination. The superior efficiency of trifluo-
romethanesulfonate anion through a comparison with
other weakly or noncoordinating counteranion was dem-
onstrated. While methanesulfonate and tetrafluoroborate
as counteranions were ineffective, change of counteranion
to hexafluroantimonate led to 73% yield of 3a (entries 8–
10). Only trace of 3a was formed by using Cu(OTf)2
which was a robust catalyst in intramolecular hydroami-
nation of alkynylsulfonamides (entry 11).11b Other metal
catalysts such as (PPh3)2NiCl2, (PPh3)2PdCl2, and
(cod)PtCl2 were ineffective (entries 12–14). Different sol-
vents were screened and toluene was found to be the most
suitable one. Other solvents, such as chloroform, THF,
and dioxane were compatible to the hydroamination. In all
case, 1-(4-methoxyphenyl)ethanone as the hydration
product could be detected due to water present in small
amounts in the reaction solution. In addition, the reaction
of 1-(4-methoxyphenyl)ethanone, instead of 1a, with 2a
did not proceed at all under the same conditions.
Abstract: In the presence of a catalytic amount of (PPh3)AuCl and
AgOTf, intermolecular hydroamination of unactivated alkynes with
sulfonamides has been shown to proceed and give N-sulfonyl
ketimines in medium to excellent yields.
Key words: hydroamination, N-sulfonyl ketimines, sulfonamide,
alkyne, gold catalysis
N-Sulfonyl imines are useful building blocks in organic
and medicinal chemistry.1 The most common method re-
ported in the literature for synthesis of these compounds
involves the condensation of carbonyl compounds with
sulfonamides.2 Syntheses of N-sulfonyl imines have also
been reported using other approaches, including the con-
densation of oximes with sulfinyl chlorides3 or sulfonyl
cyanides,4 isomerization of aziridines,5 reaction of the
carbonyl compounds with sulfinamides and following ox-
idation.6 Despite these advantages, several drawbacks re-
main associated with such reactions, including the use of
harsh acids and generating toxic byproducts in a multistep
process. Thus, development of new methods for their syn-
thesis is still needed.
Gold salts are powerful soft Lewis acids and readily pro-
mote reaction of unsaturated C–C bonds with a variety of
nucleophiles for the formation of carbon–carbon and car-
bon–heteroatom bonds.7,8 In the literature, a wide range of
metal-catalyzed inter- and intramolecular hydroamination
of alkynes are known, but the intermolecular hydroamina-
tion of alkynes with sulfonamides has not been reported
previously.9–16 On the basis of some recent studies,17 here-
in we describe an efficient gold-catalyzed intermolecular
hydroamination of unactivated alkynes with sulfonamides
to afford N-sulfonyl imines.
To further assess the scope of this process, we have exam-
ined the hydroamination of different alkynes with sul-
fonamides using the optimized reaction conditions as
described in entry 1 of Table1. The results are summa-
rized in Table2. Alkynes with an electron-donating group
on the benzene ring all gave higher the yields (entries 1–
4). In sharp contrast, with an electron-withdrawing sub-
stituent on the aromatic ring, the corresponding adduct 3g
was obtained in 40% yield (entry 6). Various aryl sulfona-
mides were then examined, not only electron-donating but
also electron-withdrawing groups on benzene ring of phe-
nylsulfonamide gave excellent yields (entries 1 and 7–10).
Under the same reaction conditions, hydroamination of al-
iphatic sulfonamides took place smoothly to afford the
corresponding N-sulfonyl ketimine 3l with 72% yield
(entry 11). In addition, p-TolSO2NHNH2 was also an
efficient substrate for hydroamination (entry 12). Further-
more, in striking contrast to aromatic alkynes, aliphatic
alkynes, such as 1-octyne and internal alkynes, such as
diphenylacetylene, failed to undergo Au-catalyzed hy-
droamination under the same conditions.
The reaction of 4-methoxyphenylacetylene (1a, 1.5
mmol) with 4-methylbenzenesufonamide (2a, 0.5 mmol)
in the presence of 2 mol% of (PPh3)AuCl and 8 mol% of
AgOTf in toluene at 100 °C proceeded efficiently to form
3a in 97% yield with perfect regioselectivity (Table1, en-
try 1). Efficient hydroamination was realized with signif-
icantly lower catalyst loading (entry 2). Investigation of
molar ratio of the starting materials revealed that an ex-
cess of alkynes (2–3 equiv) was necessary to drive the
SYNLETT 2010, No. 5, pp 0809–0811
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6.
3
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0
1
0
Advanced online publication: 10.02.2010
DOI: 10.1055/s-0029-1219384; Art ID: W16509ST
© Georg Thieme Verlag Stuttgart · New York

810
J.-Z. Zheng et al.
LETTER
Table 1 Hydroamination of 1a with 2aa
Table 2 Reaction Scope for the Hydroamination of Alkynes with
Sulfonamidesa
NTs
catalyst
PG
N
additive
MeO
+
TsNH2
toluene
100 °C, 9 h
(PPh3)AuCl
R
AgOTf
+
PG NH2
MeO
R
toluene
1a
2a
3a
1
2
3
Entry Cat. (mol%)
Additive (mol%)
AgOTf (8)
AgOTf (8)
AgOTf (8)
AgOTf (6)
AgOTf (4)
–
Yield of 3a (%)b
Entry
1
PG
R
Product
3b
3c
Yield (%)b
1
2
3c
4
5
6
7
8
9
(PPh3)AuCl (2)
(PPh3)AuCl (1)
(PPh3)AuCl (2)
(PPh3)AuCl (2)
(PPh3)AuCl (2)
(PPh3)AuCl (2)
–
97
96
88
66
50
10
35
11
trace
73
trace
0
4-TolSO2
4-TolSO2
4-TolSO2
4-TolSO2
4-TolSO2
4-TolSO2
2-TolSO2
PhSO2
4-EtO
99
77
80
78
91
40
98
91
96
99
72
63
2c
4-n-C5H11
4-n-Bu
4-Et
3c
3d
3e
4c
5c
H
3f
6c
3-F
3g
AgOTf (8)
AgOMs (8)
AgBF4 (8)
AgSbF6 (8)
–
7
4-EtO
4-MeO
4-MeO
4-MeO
4-MeO
4-EtO
3h
3i
(PPh3)AuCl (2)
(PPh3)AuCl (2)
(PPh3)AuCl (2)
Cu(OTf)2 (2)
(PPh3)2NiCl2 (2)
(PPh3)2PdCl2 (2)
(cod)PtCl2 (2)
(PPh3)AuCl (2)
(PPh3)AuCl (2)
–
8
9
4-BrPhSO2
4-IPhSO2
MeSO2
3j
10
10
11c
12c
3k
3l
11
12
–
4-TolSO2NH
3m
13
–
0
a Reaction conditions: 1 (1.5 mmol), 2 (0.5 mmol), (PPh3)AuCl (0.01
mmol), AgOTf (0.04 mmol), toluene (2 mL), 100 °C, 9 h.
b Isolated yields.
14
–
0
15d
16d
17d
AgOTf (8)
TfOH (8)
TfOH (8)
78
0
c Using 2 mL of THF as solvent.
SO2R
Ar
N
[M]
0
Ar
a Conditions: 1a (1.5 mmol), 2a (0.5 mmol), cat. (0–2 mol%), silver
salt (0–8 mol%), toluene (2 mL), 100 °C, 9 h.
H+
b Isolated yields.
c Using 1.0 mmol of 2a.
d At r.t.
Ar
NHSO2R
Ar
[M]
[Au]
H
On the basis of the experiments and precedent reports,8g,18
a plausible mechanism is shown in Scheme1. We pro-
posed that (PPh3)Au+, generated in situ from (PPh3)AuCl
and Ag+, coordinated to the alkyne to form a cationic
M(I)–alkyne complex. Then the complex underwent an
intermolecular nucleophilic attack by sulfonamide to fin-
ish the reaction.
H+
RSO2NH2
Scheme 1 Proposed mechanism for hydroamination
Acknowledgment
This work was partially supported by the Natural Science Founda-
tion of China (Nos. 20672099, 20572094).
In conclusion, we have demonstrated an efficient
(PPh3)AuCl/AgOTf-catalyzed intermolecular hydroami-
nation of unactivated alkynes with sulfonamides to pro-
duce N-sulfonyl ketimines under mild conditions with
perfect regioselectivity.19 Further efforts to expand the
scope of the chemistry and studies of the detailed mecha-
nism are currently under way in our laboratories.
References and Notes
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Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
Synlett 2010, No. 5, 809–811 © Thieme Stuttgart · New York

LETTER
Synthesis of N-Sulfonyl Imines
811
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(19) Typical Experimental Procedure
To a reactor containing sulfonamide (0.5 mmol),
(PPh3)AuCl (0.01 mmol), AgOTf (0.04 mmol), and anhyd
toluene (2 mL), was added alkyne (1.5 mmol). The mixture
was then sealed and stirred at 100 °C. After 9 h, it was
quenched with sat. soln of NaHCO3 and then with EtOAc
(3 × 10 mL), dried over Na2SO4, and concentrated in vacuo.
The residue was purified by flash chromatography to give
the pure product.
N-[1-(4-Ethoxyphenyl)ethylidene]-4-methylbenzene-
sulfonamide (3b)
Yellow solid; mp 103–105 °C. 1H NMR (500 MHz, CDCl3):
δ = 7.92–7.88 (m, 4 H), 7.32 (d, J = 8.0 Hz, 2 H), 6.86 (d,
J = 9.0 Hz, 2 H), 4.06 (q, J = 7.0 Hz, 2 H), 2.92 (s, 3 H), 2.43
(s, 3 H), 1.41 (t, J = 7.0 Hz, 3 H). 13C NMR (125 MHz,
CDCl3): δ = 178.7, 163.4, 143.3, 139.1, 130.7, 129.7, 129.4,
127.0, 114.3, 63.9, 21.6, 20.7, 14.6. IR (KBr): 2980, 2936,
2884, 1607, 1578, 1557, 1385, 1173, 1150 cm–1. HRMS
(CI): m/z calcd for C17H19NO3S [M + H]+: 318.1164; found:
318.1164.
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N-[1-(4-Methoxyphenyl)ethylidene]methane-
sulfonamide (3l)
Pale yellow solid; mp 107–108 °C. 1H NMR (500 MHz,
CDCl3): δ = 7.94 (d, J = 9.0 Hz, 2 H), 6.93 (d, J = 9.0 Hz, 2
H), 3.88 (s, 3 H), 3.22 (s, 3 H), 2.86 (s, 3 H). 13C NMR (125
MHz, CDCl3): δ = 178.9, 163.9, 130.5, 129.6, 114.0, 55.6,
43.2, 20.8. IR (KBr): 3032, 2937, 1635, 1609, 1595, 1384,
1182, 1143 cm–1. HRMS (EI): m/z calcd for C10H13NO3S
[M]+: 227.0616; found: 227.0612.
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