Catalytic coupling of aryl sulfonates with sp2-hybridized nitrogen nucleophiles: Palladium- and nickel-catalyzed synthesis of N-aryl sulfoximines

Article abstract of DOI:10.1055/s-2000-6287

Several sulfoximines have been arylated in good to high yield by palladium catalysis using aryl nonaflates and aryl triflates. Moreover, the successful synthesis of N-aryl sulfoximines from aryl tosylates is described using a Ni(COD)₂/BINAP catalyst.

Full text of DOI:10.1055/s-2000-6287

SHORT PAPER
911
Catalytic Coupling of Aryl Sulfonates with sp2-Hybridized Nitrogen
Nucleophiles: Palladium- and Nickel-catalyzed Synthesis of N-Aryl
Sulfoximines
Carsten Bolm,* Jens P. Hildebrand, Jens Rudolph
Institut für Organische Chemie der RWTH Aachen, Professor-Pirlet-Strasse 1, 52074 Aachen, Germany
Fax +49(241)8888 391; E-mail: Carsten.Bolm@oc.rwth-aachen.de
Received 13 November 1999; revised 16 February 2000
Dedicated to Professor Dr. B. Giese, Basel, with best wishes on the occassion of his 60th birthday
H
R1
R1
Pd(OAc)2,
bisphosphine
Cs2CO3, toluene,
110°C
Abstract: Several sulfoximines have been arylated in good to high
yield by palladium catalysis using aryl nonaflates and aryl triflates.
Moreover, the successful synthesis of N-aryl sulfoximines from aryl
tosylates is described using a Ni(COD)2/BINAP catalyst.
N
S
+
R2
R3
O
O
Br, I
N
S
R2
R3
2 = Me, R3 = Ph
2 = Me, R3 = Tol
Key words: palladium, nickel, sulfoximines, cross-coupling, aryl
sulfonates
1
R
R
2
Scheme 1
Palladium-catalyzed processes which employ aryl or vi-
nyl sulfonates1 are becoming increasingly attractive, be-
cause they are easily accessible from the corresponding
phenols and ketones, respectively, thus allowing an en-
tirely different class of substrates – other than aryl or vinyl
halides – to be utilized as starting materials. For example,
aryl triflates have been widely used in Heck2 and Suzuki-
Miyaura3 type couplings and more recently, they have
also been employed in the palladium-catalyzed synthesis
of aryl amines.4 An important improvement for the latter
transformation was achieved when NaOt-Bu – which was
responsible for the formation of large amounts of hydro-
lytic byproducts of the aryl triflate5 – was replaced by ce-
sium carbonate. This mild base led to both an increased
functional group tolerance and a dramatically decreased
rate of the hydrolysis of the triflate precursors.6 Compared
to aryl triflates, the corresponding nonaflates are even
more attractive substrates because they display a higher
reactivity and a more pronounced stability towards hy-
drolysis.7 Despite of all of these positive characteristics of
aryl sulfonates, palladium-catalyzed aminations of aryl
sulfonates with sp2-hybridized nitrogen nucleophiles
other than benzophenone imine are still rare.8
Reaction of aryl triflates with S-methyl-S-phenyl sulfox-
imine (1) and S-methyl-S-(p-tolyl) sulfoximine (2) under
essentially identical reaction conditions as for couplings
of aryl bromides, led to the formation of the correspond-
ing products in good to high yields (Table, Entries 1-5).
Interestingly, the substrate which is most susceptible to-
ward hydrolysis – 4-nitrophenyl triflate – gave the highest
yield of coupling product 7 at 86% indicating that triflate
hydrolysis is no serious side reaction.
Aryl nonaflates7,11 reacted also smoothly in the presence
of a catalytic amount of Pd(OAc)2/BINAP affording the
corresponding N-aryl sulfoximines in good to high yields
(Table, Entries 6-8). For example, N-(4-tert-butylphenyl)
S-methyl-S-(p-tolyl) sulfoximine was obtained with a
yield of 76%, which is remarkable taken into account that
this compound is formed in only 67% yield from the cor-
responding aryl bromide. As in reactions with aryl tri-
flates electron-deficient aryl nonaflates give the highest
yields. Thus, coupling of [3,5-bis(methoxycarbonyl)phe-
nyl] nonaflate with S-methyl-S-phenyl sulfoximine (1)
gave the N-aryl sulfoximine in 87% yield. To our delight
N-[4-(methoxycarbonyl)phenyl] S-methyl-S-phenyl sul-
foximine (8) was obtained in an excellent yield (97%),
which was again higher than that obtained in the coupling
with the corresponding aryl bromide (90%).9
Recently, we established a novel method for the catalytic
N-arylation of sulfoximines with aryl bromides and aryl
iodides which has already been applied by Harmata and
Parvi in the synthesis of benzothiazines.9,10 In this proto-
col Pd(OAc)2/BINAP serves as catalyst and cesium car-
bonate acts as base allowing for mild reaction conditions
and broad functional group tolerance (Scheme 1).
H
R1
R1
N
S
Pd- or Ni- catalyst
Herein, we report on the extension of this sulfoximine
N-arylation method first, to palladium-catalyzed reactions
of sulfoximines with aryl triflates and aryl nonaflates and
second, to nickel-catalyzed couplings of sulfoximines and
aryl tosylates.
+
R3
R4
O
O
Cs2CO3, toluene,
OSO2R2
N S
R3
110°C
R4
1, 2
3 - 12
Scheme 2
Synthesis 2000, No. 7, 911–913 ISSN 0039-7881 © Thieme Stuttgart · New York

912
C. Bolm et al.
SHORT PAPER
Table Palladium- and Nickel-catalyzed N-Arylation of Sulfox-
imines 1 and 2 with Aryl Triflates, Aryl Nonaflates, and Aryl Tos-
ylates.a
aryl nonaflates were shown to be the coupling partners of
choice giving N-aryl sulfoximines in good to excellent
yield depending on the substitution pattern of the aryl
fragment. Additionally, less reactive aryl tosylates can
also be utilized when Ni(COD)2/BINAP is used as cata-
lyst. These transformations represent a rare example of
palladium- or nickel-catalyzed arylation reactions with
sp2-hybridized nitrogen nucleophiles.9,10,14
Entry Aryl Group
(Product)
-OSO2Rb Sulfoximine Yield
[%]c
1
2
3
4
5
6
phenyl
(3)
1-naphthyl
(4)
2-naphthyl
(5)
4-tolyl
(6)
Tf
Tf
Tf
Tf
Tf
Nf
1
1
1
1
2
1
51
82
76
63
86
97
For general experimental procedures of N-arylation reactions see
reference 9. Aryl triflates were purchased from Aldrich Co. and
used as received, aryl nonaflates were prepared from the corre-
sponding phenols and nonafluorobutanesulfonylfluoride.7, 15 NMR
spectra were recorded on were recorded on a Varion VXR 300 and
a Varion Gemini 300 (at 300 MHz for 1H and 75 MHz for 13C spec-
tra) using CDCl3 as solvent and TMS as internal standart. IR spectra
were recorded on a Perkin-Elmer PE 1720 X and a Perkin Elmer PE
1760 FT.
4-nitrophenyl
(7)
4-methoxycarbonyl-
phenyl
(8)
7
8
4-tert-butylphenyl
(9)
3,5- bis(methoxy-car- Nf
bonyl)phenyl
Nf
1
1
76
87
N-(1-Naphthyl) S-Methyl-S-phenyl Sulfoximine (4)
1H NMR: d = 3.21 (s, 3H), 7.14–7.29 (m, 4H), 7.38–7.60 (m, 6H),
7.92 (m, 2H).
13C NMR: d = 46.14, 118.69, 123.83, 124.87, 125.96, 126.93,
127.52, 128.75, 128.79, 129.61, 129.67, 133.40, 134.51, 139.31,
142.92.
(10)
9d
10e
11e
4-tert-butylphenyl
(11)
4-tert-butylphenyl
(11)
4-cyanophenyl
(12)
Ts
Ts
Ts
1
1
1
41
69
35
IR (KBr): 3055, 2928, 1572, 1504, 1459, 1395, 1337, 1285, 1247,
1220, 1177, 1087, 988, 848, 777 cm-1.
MS (EI, 70 eV): m/z 281 (M+, 100%)
a Conditions: 1 equiv of aryl sulfonate, 1.2 equiv of 1 or 2 as a
0.1 molar solution in toluene at 110 °C catalyzed by Pd(OAc)2/
BINAP (5 mol%/7.5 mol%) with 1.4 equiv Cs2CO3.
b Nf = -OSO2C4F9; Tf = -OSO2CF3; Ts = -OSO2(4-tolyl).
c Yields refer to isolated yields of pure material and are an average of
at least two runs.
Anal Calcd for C17H15NOS: C, 72.57; H, 5.37; N, 4.98. Found: C,
72.80; H, 5.64; N, 4.93.
N-(2-Naphthyl) S-Methyl-S-phenyl Sulfoximine (5)
1H NMR: d = 3.24 (s, 3H), 7.04–7.10 (m, 2H), 7.29–7.31 (m, 1H),
7.38–7.49 (m, 5H), 7.70 (d, J = 8.1 Hz, 1H), 7.88–7.92 (m, 2H),
8.45 (d, J = 7.7 Hz, 1H).
d Ni(COD)2/BINAP (5 mol%/7.5 mol%) was used.
e Ni(COD)2/BINAP (10 mol%/15 mol%) was used.
13C NMR: d = 46.01, 116.61, 121.64, 124.09, 125.12, 126.00,
126.12, 127.85, 128.54, 129.63, 130.19, 133.36, 134.65, 139.44,
141.69.
MS (EI, 70 eV): m/z 281 (M+, 100%).
Finally, we were interested in the application of aryl tos-
ylates for this process. Because very active palladium-cat-
alysts for amination reactions of tosylates have been
developed in recent years we assumed that those would
also promote the reaction of sulfoximines with aryl tos-
ylates. Disappointingly, none of the tested palladium-
catalysts12 provided any product in the reaction of 1 with
4-tert-butylphenyl tosylate. However, changing the metal
source to a nickel-complex13 increased the catalytic activ-
ity notably. Thus, using Ni(COD)2/BINAP (5 mol%/7.5
mol%) afforded the desired N-aryl sulfoximine 11 in mod-
erate yield (41%). Doubling of the catalyst amount even
led to an increase in yield to satisfying 69%. Surprisingly,
the coupling with 4-cyanophenyl tosylate gave the corre-
sponding product 12 in only 35%, indicating that electron-
ic factors, which are very pronounced in palladium-
catalyzed couplings, do not influence the nickel-catalysis
to such a great extent.
IR (KBr): 3055, 2928, 1504, 1459, 1446, 1395, 1337, 1285, 1177,
1116, 1087, 988, 800 cm-1.
HRMS: Calcd for C17H15NOS, 281.087437. Found 281.087479.
N-(4-Methylphenyl) S-Methyl-S-phenyl Sulfoximine (6)
1H NMR: d = 2.12 (s, 3H), 3.13 (s, 3H), 6.68 (s, 4H), 7.39–7.48 (m,
3H), 7.88 (m, 2H).
13C NMR: d = 20.74, 45.94, 123.29, 128.74, 129.56, 129.67,
131.11, 133.20, 139.69, 142.28.
MS (EI, 70 eV): m/z 245 (M+, 100%).
IR (KBr): 2922, 1506, 1325, 1287, 1263, 1190, 1034, 748 cm-1.
Anal Calcd for C14H15NOS: C, 68.54; H, 6.16; N, 5.71. Found: C,
68.78; H, 6.29; N, 5.79.
N-(4-Nitrophenyl) S-Methyl-S-(4-methylphenyl) Sulfoximine
(7)
Mp: 122 °C.
1H NMR: d = 2.42 (s, 3H), 3.30 (s, 3H), 6.98–7.01 (d, J = 8.8 Hz,
2H), 7.33–7.36 (d, J = 8.0 Hz, 2H), 7.80–7.82 (d, J = 8.3 Hz, 2H),
7.96–7.98 (d, J = 8.8 Hz, 2H).
In summary, we have described the successful extension
of our original protocol for the palladium-catalyzed
N-arylation of sulfoximines onto aryl sulfonates. Here,
Synthesis 2000, No. 7, 911–913 ISSN 0039-7881 © Thieme Stuttgart · New York

SHORT PAPER
Catalytic Coupling of Aryl Sulfonates
913
13C NMR: d = 21.58, 46.70, 122.35, 125.11, 128.38, 130.55,
135.01, 141.52, 145.12, 152.90.
(9) a) Bolm, C.; Hildebrand, J. P. Tetrahedron Lett. 1998, 39,
5731.
b) Bolm, C.; Hildebrand, J. P. J. Org. Chem. 2000, 65, 169.
(10) Harmata, M.; Parvi, N. Angew. Chem. Int. Ed. 1999, 38, 2419.
(11) For Heck reactions utilizing aryl nonaflates see:
a) Voigt, K.; Schick, U.; de Meijere, A. Synlett 1994, 189.
b) Bräse, S.; de Meijere, A. Angew. Chem. Int. Ed. Engl. 1995,
34, 2545.
MS (EI, 70 eV): m/z 290 (M+, 52.16%), 59 (100%).
IR (cap. film): 3017, 2932, 1585, 1490, 1275 cm-1.
Anal Calcd for C14H14N2O3S: C, 57.92; H, 4.86; N, 9.65. Found: C,
57.91; H, 4.80; N, 9.58.
(12) Among the ligands used were P(t-Bu)3, Pcy3 and a
monophosphine bearing an acetal unit. For the application of
these ligands in palladium-catalyzed processes see:
a) Reddy, N. P.; Tanaka, M. Tetrahedron Lett. 1997, 38, 4807.
b) Littke, A. F.; Fu, G. C. Angew. Chem. Int. Ed. 1998, 37,
3387.
N-[3,5-Bis(methoxycarbonyl)phenyl] S-Methyl-S-phenyl Sul-
foximine (10)
1H NMR: d = 3.21 (s, 3H), 3.81 (s, 6H), 7.48–7.53 (m, 2H), 7.54–
7.56 (m, 1H), 7.76–7.78 (m, 2H), 7.90–7.93 (m, 2H), 8.09–8.11 (m,
1H).
13C NMR: d = 46.32, 52.48, 123.95, 128.44, 128.66, 129.86,
131.31, 133.74, 138.82, 146.06, 166.30.
MS (EI, 70 eV): m/z 347 (M+, 100%).
c) Littke, A. F.; Fu, G. C. J. Org. Chem. 1999, 64, 10.
d) Littke, A. F.; Fu, G. C. Angew. Chem. Int. Ed. 1999, 38,
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e) Yamamoto, T.; Nishiyama, M.; Koie, Y. Tetrahedron Lett.
1998, 39, 2367.
f) Nishiyama, M.; Yamamoto, T.; Koie, Y. Tetrahedron Lett.
1998, 39, 617.
IR (KBr): 2954, 1723, 1437, 1333, 1206, 1058, 903, 750 cm-1.
Anal Calcd for C17H17NSO5: C, 58.78; H, 4.93; N, 4.03. Found: C,
58.44; H, 4.82; N, 3.91.
g) Bei, X.; Guram, A. S.; Turner, H. W.; Weinberg, W. H.
Tetrahedron Lett. 1999, 40, 1237.
h) Bei, X.; Crevier, T.; Guram, A. S.; Jandeleit, B.; Powers, T.
S.; Turner, H. W.; Uno, T.; Weinberg, W. H. Tetrahedron
Lett. 1999, 40, 3855.
Acknowledgement
We thank the Deutsche Forschungsgemeinschaft (DFG) within the
Collaborative Research Center (SFB) 380 “Asymmetric Synthesis
by Chemical and Biological Methods“ and the Fonds der Chemi-
schen Industrie for financial support of this work. We are also gra-
teful to Degussa-Hüls AG for the generous donation of palladium
salts.
i) Bei, X.; Uno, T.; Norris, J.; Turner, H. W.; Weinberg, W.
H.; Guram, A. S. Organometallics 1999, 18, 1840.
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reactions see:
Suzuki-couplings:
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2993.
b) Saito, S.; Oh-tani, S.; Miyaura, N. J. Org. Chem. 1997, 62,
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Synthesis of phenol ethers:
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Article Identifier:
1437-210X,E;2000,0,07,0911,0913,ftx,en;C00100SS.pdf
Synthesis 2000, No. 7, 911–913 ISSN 0039-7881 © Thieme Stuttgart · New York