A mild and efficient copper-catalyzed N-arylation of unprotected sulfonimidamides using boronic acids

Article abstract of DOI:10.1016/j.tetlet.2013.11.084

An efficient and low cost copper catalyzed system for N-arylation of sulfonimidamides has been developed. The reaction proceeds at room temperature under base free conditions. Various N-aryl, N-heteroaryl, and N-cyclopropyl sulfonimidamides were obtained in good to excellent yields.

Full text of DOI:10.1016/j.tetlet.2013.11.084

Tetrahedron Letters 55 (2014) 517–520
Contents lists available at ScienceDirect
Tetrahedron Letters
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A mild and efficient copper-catalyzed N-arylation of unprotected
sulfonimidamides using boronic acids
b
c
S. R. K. Battula a, , G. V. Subbareddy , I. E. Chakravarthy
⇑
a Department of Chemistry, Jawaharlal Nehru Technological University, Anantapur 515002, Andhra Pradesh, India
b Department of Chemistry, Jawaharlal Nehru Technological University Anantapur College of Engineering Pulivendula, 51639 YSR(Kadapa) Dist, Andhra Pradesh, India
c Department of Chemistry, Rayalaseema University, Kurnool 518002, Andhra Pradesh, India
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient and low cost copper catalyzed system for N-arylation of sulfonimidamides has been devel-
oped. The reaction proceeds at room temperature under base free conditions. Various N-aryl, N-hetero-
aryl, and N-cyclopropyl sulfonimidamides were obtained in good to excellent yields.
Ó 2013 Elsevier Ltd. All rights reserved.
Received 23 September 2013
Revised 16 November 2013
Accepted 18 November 2013
Available online 28 November 2013
Keywords:
Sulfonimidamides
Chan–Lam coupling
Boronic acids
Copper-catalyzed coupling
N-arylation
The chemistry of sulfonamide has been widely explored due to
their application in the synthesis of biologically active molecules in
drug discovery.1 Surprisingly, the analogous sulfonimidamides
have been explored to a lesser extent. Sulfonimidamides, which
has a nitrogen atom in place of oxygen, were shown as bioisostere
of sulfonamide in medicinal chemistry.2 Sulfonimidamides are ex-
plored in the synthesis of biologically active compounds, such as
oncolytic sulfonylureas3 and for the preparation of tetrahedral
transition state analogues of aspartic acid and metallo protease.4
Sulfonimidamides containing compounds are reported as pesti-
cidal agents5 and also as sodium channel antagonists.6
approachreported by Bolm et al.15 In subsequent investigations,
they have developed an efficient catalyst system for N-arylation
of unprotected sulfonimidamides with aryl bromides using 3 mol
% of palladium catalyst (Ru–Phos precatalyst). An efficient copper
catalyzed N-arylation of N-protected sulfonimidamides was re-
ported by Bolm16 and Malacria17 using aryl halide. Later Arvidsson
explored the synthesis of aryl and heteroaryl acyl sulfonimida-
mides by palladium catalyzed carbonylation.18 Though these
methods are very useful and efficient it would be desirable to uti-
lize an environmentally benign catalyst system for this transfor-
mation. In addition to this an alternate substrate in place of aryl
halides that could facilitate a chemo selective reaction in the pres-
ence of reactive functional groups would be advantageous. Our
intention was to explore the utility of the well documented
Chan–Lam coupling reaction in the synthesis of N-arylated sulfon-
imidamides. Herein we wish to report the results of copper cata-
lyzed coupling of unprotected sulfonimidamides with arylboronic
acids as an alternative to Pd catalyst and aryl halides.
Highly efficient methodology for the synthesis of Boc protected
sulfinamide 1 was established by Bolm and coworkers19 Arvidsson
and coworkers, later stabilized the synthesis of Boc protected sulf-
onimidamides 2 by oxidative chlorination of protected sulfinamide
1 using NCS (3.0 equiv) in acetonitrile, followed by amination of
the resulting sulfinimidoyl chloride with morpholine in situ.14
The reported yield for this reaction over two steps was 61% after
43 h. We were able to improve the yield and time with a slight
modification of this procedure (Scheme 1).
Sulfonimidamides were first reported in 1960 by Levechenko.
This found some application in organic synthesis, such as azirida-
tion of olefins,7 imination of sulfides,8 and C–H amination of hydro-
carbons.9 Bolm and coworkers explored the use of
sulfonimidamides in organocatalytic asymmetric aldol reactions10
and as a chiral ligand in enantioselective Henry reaction.11 Recent
studies were reported in asymmetric hydrogenation of cyclic ena-
mides by using rhodium and iridium complexes of sulfonimidam-
ido-based phosphoramidites (SIAPhos).12
Unprotected sulfonimidamides (Fig. 1, R3 = H, R1, R2 – H)
were initially reported by Johnson et al. 13and later Arvidsson
et al.14 developed an efficient synthetic route based on the
⇑
Corresponding author. Tel.: +91 9014952677; fax: +91 8568212314.
E-mail address: srkbattula99@yahoo.com (S.R.K. Battula).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.11.084

518
S. R. K. Battula et al. / Tetrahedron Letters 55 (2014) 517–520
R3
R2
Table 1
O
R
N
N
Synthesis of unprotected sulfonimidamides
S
boc
O
S
N
N
NH
N
O
O
TFA, DCM
rt, 15h
i) NCS, MeCN
rt, 1h
S
S
R1
R2
R2
boc
N
H
ii) R1R2NH, MeCN
rt, 1h
R1
R1
Unprotected sulfonimidamides (R3 = H, R1,R2= Alkyl)
N-protected sulfonimidamides (R1,R2= H, R3= PG)
1
2 a-d
3 a-d
Yieldb (%)
Figure 1. Structure of sulfonimidamides.
Entry
1
Product
Yielda (%)
Product*
boc
NH
N
O
S
O
N
N
S
90
89
The previous reaction was reported without isolating inter-
O
3a
mediate 1a. In our modified procedure, compound 1a was iso-
lated by an aqueous workup after the oxidative chlorination
and morpholine was added to a solution of crude product in ace-
tonitrile. The yields for Boc-protected sulfonimidamides 2a were
improved up to 89% and the reaction time was reduced to 2 h
(Table 1, entry 1).20 The substrate scope was tested with various
secondary amines and the results of this reaction are summa-
rized in Table 1. Good yields were obtained for piperidine
(Table 1, entry 2), pyrrolidine (Table 1, entry 3), and diethyl
amine (Table 1, entry 4). Finally unprotected sulfonimidamides
3a–d21 were obtained by deprotection of Boc using TFA in
DCM as reported earlier.
The next goal was to perform the N-arylation of the above pre-
pared sulfonimidamides using Cham–Lam coupling reaction. Our
investigation started with the coupling of 4-(phenylsulfonimi-
doyl)morpholine 3a and phenyl boronic acid 4 in dichloromethane
solvent using different copper salts.
Based on the initial results as depicted in Table 2 anhydrous
copper acetate was found to be the optimum catalyst for this trans-
formation and showed best results under base-free conditions but
the reaction took 48 h to complete in DCM (Table 2, entry 4). Other
copper salts such as CuCl and CuSO4 (anhydrous) also worked but
the purification of the product took longer time due to some close
impurities formed in the reaction (Table 2, entry 1 and 2) and did
not work when CU-TMEDA was used as the catalyst (Table 2, entry
3). The reaction worked well when MeOH was used as solvent at
room temperature with Cu(OAc)2 (Table 2, entry 5) and CuSO4
(Table 2, entry 10) gave moderate yields. CuCl (Table 2, entry 11)
was inactive under the same conditions. We next studied the effect
of catalyst loading and the arylboronic acids. Best results were ob-
tained with 10 mol % of copper acetate and 2.3 equiv of boronic
acid under base free conditions (Table 2, entry 3). Having
optimized the reaction conditions22 we next explored the scope
of the reaction with various arylboronic acids. The results of this
are summarized in Table 3.
O
2a
boc
NH
N
O
S
O
O
O
N
S
N
2
3
89
89
88
88
3b
2b
boc
boc
O
O
NH
N
N
N
S
S
S
3c
2c
NH
N
N
S
N
4
86
81
3d
2d
Reaction conditions:
(i) NCS (3.0 equiv), MeCN, rt, 1 h. (ii) R1R2NH (2.5 equiv), MeCN, rt, 1 h:
TFA, DCM, rt, 15 h. All the reactions were started with 2 g scale.
Product after deprotection of Boc group.
a
b
*
nature of the substitution (Table 3, 5b–f). Moderate yields of the
products were obtained with ortho substituted arylboronic acid
(Table 3, 5h) but it was poor with a bulkier ortho substituent
(Table 3, 5g). It is noteworthy that many reactive functional groups
such as bromo, ester, cyano, and methanesulfonyl (Table 3, 5c–f)
were tolerated in the above mentioned reaction conditions. The
resultant products could be further derivatized using standard
transformations known for these functional groups.
Heterocyclic boronic acids reacted well under these conditions.
Good yields were obtained for 3-pyridyl, pyrimidin-5-yl, and 3-thi-
ophene boronic acids (Table 3, 5i–k). Cyclopropylboronic acid did
not react under the optimized reaction conditions. It worked well
in the presence of a ligand and base under heating conditions
(Cu(OAc)2 (1.0 equiv), bipyridyl (0.8 equiv), Na2CO3, DCE, 90 °C,
3 h, sealed tube) (Table 3, 5l).
As can be seen from Table 3 good results were obtained with
arylboronic acids with para substitution despite the electronic
The optimized reaction conditions21 were also applied to alter-
natively substituted unprotected sulfonimidamides (Fig 1, R3 = H)
such as N-(phenylsulfonimidoyl)piperidine 3b, N-(phenylsulfo-
nimidoyl)pyrrolidine 3c and N-(phenylsulfo-nimidoyl)diethyl 3d.
N-arylation of these three sulfonimidamides showed good results
with phenyl, 4-bromophenyl, and 4-methanesulfonylphenylboron-
ic acids (Table 4, 6a–i).
O
S
N
O
O
boc
N
boc
R2
R1R2NH, MeCN
rt, 1h
S
NCS, MeCN
rt, 1h
boc
S
Cl
N
H
N
R1
1
2
1a
In conclusion, we have improved the yield of sulfonimidamides
by modifying the existing procedure with a reduced reaction time.
We have enabled a low-cost catalyst system as an alternative to
the palladium catalyst for N-arylation of unprotected sulfonimida-
mides. Boronic acids were used in place of aryl halides which were
useful especially in the case of substrates containing reactive func-
tional groups. Excellent yields were obtained with aryl, heteroaryl,
and cyclopropyl boronic acids. This method would compare well
and complement existing methods.
TFA, DCM
rt, 15h
O
NH
S
R2
N
R1
3
Scheme 1. Synthesis of unprotected sulfonimidamides 3.

S. R. K. Battula et al. / Tetrahedron Letters 55 (2014) 517–520
519
Table 2
N-arylation of sulfonimidamides 3a with phenyl-boronic acid 4 using different copper salts and different conditions
OH
B
OH
O
NH
N
O
N
N
S
4
S
O
O
3a
5a
Entry
Conditionsa
4 (equiv)
Temp (°C)
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
CuSO4 (10 mol %), DCM
CuCl (10 mol %), DCM
2.3
2.3
2.3
2.3
2.3
2.3
2.3
1.0
2.0
2.3
2.3
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
18
15
24
48
24
24
8
24
24
24
24
75
70
0
Cu-TMEDA (10 mol %), DCM
Cu(OAc)2 (10 mol %), DCM
Cu(OAc)2 (10 mol %), MeOH
Cu(OAc)2 (5 mol %), MeOH
Cu(OAc)2 (1.0 equiv), MeOH
Cu(OAc)2 (10 mol %), MeOH
Cu(OAc)2 (10 mol %), MeOH
CuSO4 (10 mol %), MeOH
CuCl (10 mol %), MeOH
68
86
70
78
40
73
70
0
9
10
11
a
Anhydrous salts CuSO4 and Cu(OAc)2 were used.
All yields are based on isolated product.
b
Table 3
Table 4
N-arylation of sulfonimidamides 3a with different boronic acids using anhydrous
N-arylation of sulfonimidamides 3 with arylboronic acids using anhydrous Cu(OAc)2
Cu(OAc)2 as a catalyst
as a catalyst
OH
OH
R
B
B
Ar
R
OH
N
N
O
Ar
OH
N
N
O
O
NH
N
O
NH
N
4a-o
S
S
S
R2
Cu(OAc)2 (10 mol %),
MeOH, rt, 24h
S
Cu(OAc)2 (10 mol %),
MeOH, rt, 24h
R2
R1
R1
O
O
5 a-l (yield %)a
3a
6 a-i (yield %)a
3
OMe
CO2Me
Br
SO2Me
N
N
O
O
N
N
S
O
N
N
N
N
O
S
S
O
N
N
O
N
N
S
S
S
O
O
O
5a
5b (82%)
5c
6a (84%)
6c (81%)
6b (76%)
SO2Me
CN
Br
Br
SO2Me
O
N
O
N
N
N
N
N
O
O
O
N
S
N
O
S
N
N
S
S
S
S
N
N
O
O
O
O
O
6d (85%)
5e
5d (85%)
6e (78%)
6f (84%)
5f (80%)
Br
SO2Me
MeO2C
O2N
N
N
N
O
O
S
N
N
N
N
N
N
O
O
S
O
N
N
O
N
S
N
S
S
S
O
O
O
6g (81%)
5i (74%)
5h (40%)
5g (5%)b
6h (75%)
6i (80%)
N
a
S
All yields are based on isolated product.
N
N
N
O
N
N
O
S
N
N
O
S
S
References and notes
O
5l (76%)c
5k (84%)
5j (70%)
1. (a) Ali, A.; Reddy, G. S. K. K.; Cao, H.; Anjum, S. G.; Nalam, M. N. L.; Schiffer, C. A.;
Rana, T. M. J. Med. Chem. 2006, 49, 7342–7356; (b) McCarroll, A. J.; Bradshaw, T.
D.; Westwell, A. D.; Matthews, C. S.; Stevens, M. F. G. J. Med. Chem. 2007, 50,
1707–1710; (c) Wilkinson, B. L.; Bomaghi, L. F.; Houston, T. A.; Innocenti, A.;
Vullo, D.; Supuran, C. T.; Poulsen, S. A. J. Med. Chem. 2007, 50, 1651–1657;
a
b
c
All yields are based on isolated product.
Yield based on LCMS and compound was not isolated.
Cu(OAc)2 (1.0 equiv), Bipyridyl (0.8 equiv), Na2CO3, DCE, 90 °C, 3 h, sealed tube.

520
S. R. K. Battula et al. / Tetrahedron Letters 55 (2014) 517–520
(d) Drews, J. Science 2000, 287, 1960–1964; (e) Boyd, A. E. Diabetes 1988, 37,
847–850.
2. Sehgelmeble, F.; Janson, J.; Ray, C.; Rosqvist, S.; Gustavsson, S.; Nilsson, L.;
Minidis, A.; Holenz, J.; Rotticci, D.; Lundkvist, J.; Arvidsson, P. I. Chem. Med.
Chem. 2012, 7, 396–399.
yield 2a (2.4 g, 90%) as a white solid.
Mp = 103–105 °C. 1H NMR (400 MHz, CDCl3) d 7.86 (d, J = 7.2 Hz, 2H), 7.63 (t,
J = 7.2 Hz, 1H), 7.56 (t, J = 7.6 Hz, 2H), 3.73 (t, J = 4.4 Hz, 4H), 3.13–3.12 (m, 4H),
1.39 (s, 9H); 13C NMR (100 MHz, CDCl3) d 156.2, 135.4, 133.2, 129.2, 127.8,
80.5, 66.1, 45.7, 27.9; MS (ES–MS) m/z 327.2 (M+H)+.
3. Toth, J. E.; Grindey, G. B.; Ehlhardt, W. J.; Ray, J. E.; Boder, G. B.; Bewley, J. R.;
Klingerman, K. K.; Gates, S. B.; Rinzel, S. M.; Schultz, R. M.; Weir, L. C.; Worzalla,
J. F. J. Med. Chem. 1997, 40, 1018–1025.
Data are identical to those in reference: Maldonado, M.F.; Sehgelmeble, F.;
Bjarnemark, F.; Svensson, M.; Ahman, J.; Arvidsson, P.I. Tetrahedron. 2012, 68,
7456–7462.
4. Cathers, B.; Schloss, J. V. Bioorg. Med. Chem. Lett. 1999, 9, 1527–1531.
5. Paulini, R. (BASF SE, Ludwigshafen, Germany), WO 2009/156336 A1, 2009; (b)
Paulini, R. (BASF SE, Ludwigshafen, Germany), WO 2011/069955 A1, 2011.
6. Kleemann, H. W. (Hoechst AG, Frankfurt am Main, Germany), EP0771788 A2,
1997; (b) Kleemann, H. W. (Hoechst AG, Frankfurt am Main, Germany),
US6057322 A, 2000.
7. (a) Leca, D.; Toussaint, A.; Mareau, C.; Fensterbank, L.; Lacote, E.; Malacria, M.
Org. Lett. 2004, 6, 3573–3575; (b) Di Chenna, P. H.; Robert-Peillard, F.; Dauban,
P.; Dodd, R. H. Org. Lett. 2004, 6, 4503–4505; (c) Fruit, C.; Robert-Peillard, F.;
Bernardinelli, G.; Müller, P.; Dodd, R. H.; Dauban, P. Tetrahedron Asymm. 2005,
16, 3484–3487.
8. Collet, F.; Dodd, R. H.; Dauban, P. Org. Lett. 2008, 10, 5473–5476.
9. (a) Collet, F.; Lescot, C.; Liang, C.; Dauban, P. Dalton Trans. 2010, 39, 10401–
10413; (b) Lian, C.; Collet, F.; Robert-Peillard, F.; Muller, P.; Dodd, R. H.;
Dauban, P. J. Am. Chem. Soc. 2008, 130, 343–350; (c) Liang, C.; Robert-Peillard,
F.; Fruit, C.; Müller, P.; Dodd, R. H.; Dauban, P. Angew. Chem. 2006, 45, 4757–
4760. Angew. Chem., Int. Ed. 2006, 45, 4641–4644; (d) Tsushima, S.; Yamada, Y.;
Oshima, K.; Chaney, M. O.; Jones, N. D.; Swartzendruber, J. K. Bull. Chem. Soc.
Jpn. 1989, 62, 1167–1178.
21. General procedure for the synthesis of 4-(phenylsulfonimidoyl)-morpholine 3a: To
a solution of 2a (1.0 g, 3.06 mmol) in dichloromethane (25 ml), trifluoroacetic
acid (12 ml, 15.0 mmol) was added at 0 °C and the mixture was stirred at room
temperature for overnight. The solvent was removed and the product was
purified by flash chromatography to yield 3a (0.62 g, 89%) as a white solid.
Mp = 104–106 °C. 1H NMR (400 MHz, DMSO-d6) d 7.88 (d, J = 7.2 Hz, 2H), 7.59
(t, J = 7.2 Hz, 1H), 7.53 (t, J = 8.0 Hz, 2H), 3.71 (t, J = 4.4 Hz, 4H), 2.99 (t,
J = 4.4 Hz, 4H), 1.90 (br s, 1H); 13C NMR (100 MHz, CDCl3) d 135.1, 132.5, 128.8,
128.0, 66.4, 47.0; IR (neat): 3567, 3272, 2858, 1636, 1447, 1257, 1082, 934,
727 cmÀ1; MS (ES–MS) m/z 227.1 (M+H)+.
Data are identical to those in reference: Maldonado, M.F.; Sehgelmeble, F.;
Bjarnemark, F.; Svensson, M.; Ahman, J.; Arvidsson, P.I. Tetrahedron. 2012, 68,
7456–7462.
Spectral data for compounds 3b–d.
Compound 3b: Off-white solid; Mp = 112–113 °C. 1H NMR (400 MHz, DMSO-d6)
d 7.74 (d, J = 7.6 Hz, 2H), 7.63–7.54 (m, 3H), 4.23 (s, 1H), 2.82– .81 (m, 4H),
1.49–1.47 (m, 4H), 1.31–1.28 (m, 2H); 13C NMR (100 MHz, CDCl3) d 136.3,
132.0, 128.6, 127.9, 47.8, 25.6, 23.6; IR (neat): 3611, 3282, 3058, 2938, 2826,
1445, 1254, 1213, 1138, 1066, 970, 919, 760 cmÀ1; MS (ES–MS) m/z 225.0
(M+H)+.
10. Worch, C.; Bolm, C. Synlett 2009, 2425–2428.
11. Steurer, M.; Bolm, C. J. Org. Chem. 2010, 75, 3301–3310.
12. Patureau, F. W.; Worch, C.; Siegler, M. A.; Spek, A. L.; Bolm, C.; Reek, J. N. H. Adv.
Synth. Catal. 2012, 354, 59–64.
13. (a) Johnson, C. R.; Lavergne, O. J. Org. Chem. 1989, 54, 986–988; (b) Johnson, C.
R.; Lavergne, O. J. Org. Chem. 1993, 58, 1922–1923.
14. Maldonado, M. F.; Sehgelmeble, F.; Bjarnemark, F.; Svensson, M.; Ahman, J.;
Arvidsson, P. I. Tetrahedron 2012, 68, 7456–7462.
15. Bolm, C.; Garcia Machenco, O. Beilstein J. Org. Chem. 2007, 3, 25.
16. Bolm, C.; Worch, C. Synthesis 2008, 5, 739–742.
17. Azarro, S.; Desage-El Murr, M.; Fensterbank, L.; Laco, E.; Malacria, M. Synlett
2011, 5, 849–851.
18. Borhade, S. R.; Sandstrom, A.; Arvidsson, P. I. Org. Lett. 2013, 15, 1056–1059.
19. Worch, C.; Atodiresei, I.; Raabe, G.; Bolm, C. Chem. Eur. J. 2010, 16, 677–683.
20. General procedure for the synthesis of tert-butyl[morpholin-4-yl(oxido)phenyl-
Compound 3c: Off-white solid; Mp = 92–93 °C. 1H NMR (400 MHz, DMSO-d6) d
7.84 (d, J = 7.2 Hz, 2H), 7.63–7.54 (m, 3H), 4.34 (br s, 1H), 3.06–3.02 (m, 4H),
1.58–1.55 (m, 4H); 13C NMR (100 MHz, CDCl3) d 137.2, 132.1, 128.7, 127.8,
48.6, 25.2; IR (neat): 3598, 3289, 3073, 2973, 2875, 1627, 1472, 1447, 1254,
1125, 1070, 1003, 767 cmÀ1; MS (ES–MS) m/z 211.1 (M+H)+.
Compound 3d: pale yellow oil. 1H NMR (400 MHz, DMSO-d6)
d 7.81 (d,
J = 6.8 Hz, 2H), 7.58–7.50 (m, 3H), 4.16 (br s, 1H), 3.19–3.05 (m, 4H), 0.97 (t,
J = 7.2 Hz, 6H); 13C NMR (100 MHz, CDCl3) d 140.7, 131.6, 128.6, 127.0, 42.6,
14.3; IR (neat): 3587, 3284, 3065, 2975, 2935, 2873, 1635, 1446, 1382, 1345,
1247, 1195, 1132, 1010, 757 cmÀ1; MS (ES–MS) m/z 213.2 (M+H)+.
22. General procedure for N-arylation of unprotected sulfonimidamides 3a-d using
aryl(heteroaryl)boronic acid: To a stirred solution of compound 3a-d (1.0 equiv)
in MeOH were added aryl(heteroaryl)boronic acid (2.3 equiv) and Cu(OAc)2
(10 mol %) and the reaction mixture was stirred under air atmosphere. The
reaction mixture was monitored by TLC/LCMS. After the disappearance of
starting material, the reaction mixture was filtered through a celite pad and the
filtrate was concentrated to get crude product. The product was purified using
flash chromatography.
sulfanylidene]carbamate 2a: To
a
stirred solution of tert-butyl
phenylsulfinylcarbamate 1 (2 g, 8.29 mmol) in acetonitrile was added NCS
(3.32 g, 24.87 mmol) at 0 °C. The reaction mixture was stirred for 1 h at room
temperature and was monitored by TLC. After disappearance of starting
material, it was diluted with cold water and extracted with EtOAc (3 Â 100 ml).
The combined organic extract was washed with water, brine solution, dried on
anhydrous Na2SO4 and filtered. The solvent was removed under reduced
pressure to afford crude product 1a. To a solution of crude 1a in acetonitrile
was added morpholine (1.79 ml, 20.72 mmol) at 0 °C. The reaction mixture was
stirred for 1 h at room temperature and was monitored by TLC. After
disappearance of starting material, it was diluted with cold water, and
extracted with EtOAc (3 Â 100 ml). The combined organic extract was
washed with water, brine solution, dried on anhydrous Na2SO4, and filtered.
The solvent was removed under reduced pressure to afford the crude product
which was purified using flash chromatography using 40% EtOAc/hexane to
Spectral data for representative data.
4-(N,S-Diphenylsulfonimidoyl)morpholine (5a): Mp = 110–113 °C. 1H NMR
(400 MHz, DMSO-d6) d 7.90 (d, J = 7.6 Hz, 2H), 7.74–7.70 (m, 1H), 7.67–7.64
(m, 2H), 7.21 (t, J = 8.0 Hz, 2H), 7.12 (d, J = 8.0 Hz, 2H), 6.93 (t, J = 7.2 Hz, 1H),
3.56–3.44 (m, 4H), 2.92–2.86 (m, 4H); 13C NMR (100 MHz, CDCl3) d 143.3,
135.2, 132.6, 129.0, 128.9, 128.0, 123.6, 122.0, 66.1, 46.6; MS (ES–MS) m/z
303.2 (M+H)+.
Data are identical to those in reference: Maldonado, M.F.; Sehgelmeble, F.;
Bjarnemark, F.; Svensson, M.; Ahman, J.; Arvidsson, P.I. Tetrahedron. 2012, 68,
7456–7462.