A novel, easy and mild preparation of sulfilimines from sulfoxides using the Burgess reagent

Article abstract of DOI:10.1016/j.tetlet.2008.04.152

A novel preparation of sulfilimines from the corresponding sulfoxides using the Burgess reagent is described. The reaction is general to dialkyl- and aryl alkyl sulfoxides and proceeds under mild conditions in benzene. A variety of protecting groups can be introduced on the nitrogen of the sulfilimine by choosing the appropriate Burgess reagent.

Full text of DOI:10.1016/j.tetlet.2008.04.152

Tetrahedron Letters 49 (2008) 4256–4259
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A novel, easy and mild preparation of sulfilimines from sulfoxides
using the Burgess reagent
*
Sadagopan Raghavan , Shaik Mustafa, Kailash Rathore
Organic Division I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel preparation of sulfilimines from the corresponding sulfoxides using the Burgess reagent is
described. The reaction is general to dialkyl- and aryl alkyl sulfoxides and proceeds under mild conditions
in benzene. A variety of protecting groups can be introduced on the nitrogen of the sulfilimine by choos-
ing the appropriate Burgess reagent.
Received 27 March 2008
Revised 23 April 2008
Accepted 26 April 2008
Available online 1 May 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Sulfilimines
Sulfoxide
Burgess reagent
Chiral sulfilimines,1 the nitrogen analogs of sulfoxides, are an
interesting class of compounds whose chemistry remains underde-
veloped partly because of the limited methods available for their
preparation. Chiral sulfilimines have been prepared by kinetic res-
olution of racemic sulfilimines,2 from the corresponding sulfox-
ides,3 and from sulfides by nitrene transfer.4 In continuation of
our interest in the chemistry of sulfilimines,5 we sought a route
to sulfilimines possessing protecting groups that are removable
under mild conditions so that they would be synthetically useful
as inter-6 and intramolecular nucleophiles,5 from the correspond-
ing sulfoxides,7 which are readily available. In connection with
another project, to secure cyclohexene derivative 2, we subjected
tertiary alcohol 1 to treatment with the Burgess reagent8 3b under
standard conditions.9 However, TLC analysis did not reveal less
polar spot and further analysis indicated that we had not obtained
2 but polar sulfilimine 4 instead (Scheme 1). This discovery
prompted us to examine the generality of this transformation
and the results of this investigation are reported herein.
Initially, racemic methyl p-tolyl sulfoxide 5a was reacted with
the Burgess reagent 3a9f (1 equiv) in anhydrous THF (0.2 M) at
60 °C. After 2 h, sulfilimine 6a was isolated in 30% yield along with
unreacted 5a and methyl p-tolyl sulfide (7, Table 1).
The use of excess of 3a (2 equiv) relative to 5a led to the com-
plete consumption of the latter to furnish 6a in 72% yield along
with methyl p-tolyl sulfide 7 in 10% yield. The reaction of 5a with
3a proceeded at rt in both acetonitrile and dichloromethane, with
an excess of 3a being required for completion over a 5–7 h period.
Interestingly, when the reaction was carried out in benzene, con-
version was observed at 0 °C and complete conversion was
observed in 5 h to yield 6a in 80% yield. The same reaction at rt
was complete within 2 h affording 6a in 85% yield. Having stan-
dardized the reaction conditions,10 the generality of the procedure
was examined employing a variety of aryl alkyl and di-alkyl sulfox-
ides (Table 2). A perusal of Table 2 reveals that the reaction is gen-
eral, high yielding and proceeds under mild conditions. The
reaction proceeds with equal facility on sulfoxides with electron
O
NCO2Me
S
O
S
S
p
-Tol
p-Tol
p
-Tol
3b, THF
OH
OH
3b, THF
4
2
1
Scheme 1.
* Corresponding author. Tel.: +91 040 27160123; fax: +91 040 27160512.
E-mail addresses: sraghavan@iict.res.in, purush101@yahoo.com (S. Raghavan).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.04.152

S. Raghavan et al. / Tetrahedron Letters 49 (2008) 4256–4259
4257
Table 1
Reaction of 5a with 3a in different solventsa
O
S
O
O
S
NCO2Bn
Solvent
Bn
S
S
+
+
NEt3
N
O
p-Tol
Me
p
-Tol
Me
p-Tol
Me
O
3a
Temperature
6a
5a
7
Entry
Equiv of 3a
Solvent
Temp in °C (Time in h)
Yieldb (%)
1
2
3
4
5
6
7
8
9
1
1
2
1
2
1
2
1
2
2
THF
THF
THF
CH3CN
CH3CN
CH2Cl2
CH2Cl2
PhH
rt
No Rxn
30c
72d
32c
68d
30c
65d
30c
80
60 (2)
60 (1.5)
rt (6)
rt (5)
rt (7)
rt (6)
0 to rt (7)
0 to rt (5)
rt (2)
PhH
PhH
10
85
a
All reactions were run using 0.5 mmol of 5a, 0.2 M in solvent.
Isolated yield.
Starting material ca. 60% was recovered.
10–15% of sulfide 7 was isolated.
b
c
d
Table 2
Reaction of sulfoxides with Burgess reagents
NCO2R3
S
O
S
O
O
S
Benzene
rt
R3
O
R1
R2
+
R1
R2
NEt3
N
O
6
3a, R3 = Bn; 3b, R3 = Me
5
3c, R3 = Allyl; 3d, R3 = CH2CCl3
Entry
1
Burgess reagent
Sulfoxide
Sulfilimine
Yield (%)
85
NCO2Bn
O
S
3a
S
p
-Tol
Me
6a
p-Tol
Me
5a
O
S
NCO2Bn
S
2
3
3a
80
82
Me
Me
6b
5b
MeO
Br
MeO
Br
O
NCO2Bn
S
S
3a
3a
Me
Me
5c
6c
NCO2Bn
O
S
S
Me
Me
4
70
OMe
OMe
5d
6d
NCO2Bn
O
S
S
5
6
3a
3a
85
82
Me
Me
5e
6e
O
NCO2Bn
S
S
Me
Me
O2N
Me
O2N
6f
5f
O
NCO2Bn
S
S
7
3a
90
Me
Me
Me
5g
6g
(continued on next page)

4258
S. Raghavan et al. / Tetrahedron Letters 49 (2008) 4256–4259
Table 2 (continued)
Entry
Burgess reagent
Sulfoxide
Sulfilimine
Yield (%)
70
O
S
NCO2Bn
S
8
9
3a
MeO
Me
MeO
Me
5h
6h
NCO2Me
O
S
S
3b
Me
78
Me
5b
MeO
MeO
6i
NCO2Allyl
O
S
S
10
11
3c
3c
85
76
p-Tol
Me
p
-Tol
Me
5a
6j
O
S
NCO2Allyl
S
MeO
Me
Me
MeO
Me
5h
6k
NCO2CH2CCl3
O
S
S
12
3d
70
Me
Br
Br
5c
6l
O
BnO2C
Me
N
S
S
O
NCO2Bn
S
SO3
+
+
O
p
-Tol
Me
p
-Tol
Retention
I
5a + 3a
BnO2C
Me
O
NCO2Bn
S
O
N
S
SO3
p
-Tol
Me
S
N CO2Bn
O
S
O
Inversion
p
-Tol
O
II
Scheme 2.
O
NCO2Bn
Me
O
S
Me
S
O
O
S
p
-Tol
p
-Tol
III
O
S
O
O
S
O
or
+
3a
S
+
p-Tol
Me
p-Tol
Me
NEt3
N
O
O
Bn
(-)-5a
(+)-5a
3a
Me
O
S
O
O
S
NCO2Bn
p-Tol
IV
Scheme 3.

S. Raghavan et al. / Tetrahedron Letters 49 (2008) 4256–4259
4259
donating (entries 2, 4 and 9), electron withdrawing substituents
References and notes
(entries 3, 6 and 12) and an o-substituted sulfoxide (entry 4).
Also the reaction was general for a variety of Burgess reagents
3a–d9f thus furnishing sulfilimines with different protecting
groups.
The reaction probably proceeds via intermediates I and/or
II (indicated for one of the enantiomers) to afford 6a with
retention or inversion of the sulfur configuration, respectively
(Scheme 2).
1. (a) Gilchrist, T. L.; Moody, C. J. Chem. Rev. 1977, 77, 409; (b) Johnson, C. R. In
Comprehensive Organic Chemistry; Barton, D. H. R., Ollis, W. D., Eds.; Pergamon:
New York, 1979; Vol. 3, Section 11.10; (c) Koval, I. V. Russ. Chem. Rev. 1990, 59,
819.
2. Annunziata, R.; Cinquini, M.; Colonna, S.; Cozzi, F. J. Chem. Soc., Perkin Trans. 1
1981, 3118.
3. (a) Day, J.; Cram, D. J. J. Am. Chem. Soc. 1965, 87, 4398; (b) Schultz, G.; Kresze, G.
Angew. Chem., Int. Ed. 1963, 2, 1022; (c) Rayner, D. R.; von Schriltz, D. M.; Day, J.;
Cram, D. J. J. Am. Chem. Soc. 1968, 90, 2721; (d) Wucherpfennig, W.; Kresze, G.
Tetrahedron Lett. 1966, 1671; (e) Appel, R.; Rittersbacher, H. Chem. Ber. 1964, 97,
852; (f) King, C. J. Org. Chem. 1960, 25, 352; (g) Neidlein, R.; Haussmann, W.
Angew. Chem., Int. Ed. 1965, 4, 708.
4. (a) Takada, H.; Nishibayashi, Y.; Ohe, K.; Uemura, S. Chem. Commun. 1996, 931;
(b) Takada, H.; Nishibayashi, Y.; Ohe, K.; Uemura, S.; Baird, C. P.; Sporey, T. J.;
Taylor, P. C. J. Org. Chem. 1997, 62, 6512; (c) Baird, C. P.; Clark, A. J.; Rooke, S. M.;
Sparey, T. J.; Taylor, P. C. Phosphorus, Sulfur Silicon Relat. Elem. 1997, 120 and
121, 365; (d) Miyake, Y.; Takada, H.; Ohe, K.; Uemura, S. J. Chem. Soc., Perkin
Trans. 1 1998, 2373; (e) Nishikori, H.; Ohta, C.; Oberlin, E.; Irie, R.; Katsuki, T.
Tetrahedron 1999, 55, 13937; (f) Ohta, C.; Katsuki, T. Tetrahedron Lett. 2001, 42,
3885; (g) Murakami, M.; Uchida, T.; Katsuki, T. Tetrahedron Lett. 2001, 42, 7071;
(h) Tomooka, C. S.; Carreira, E. M. Helv. Chim. Acta 2002, 85, 3773; (i) Tamura,
Y.; Uchida, T.; Katsuki, T. Tetrahedron Lett. 2003, 44, 3301; (j) Uchida, T.;
Tamura, Y.; Ohba, M.; Katsuki, T. Tetrahedron Lett. 2003, 44, 7965.
5. (a) Raghavan, S.; Naveen Kumar, Ch.; Tony, K. A.; Ramakrishna Reddy, S.;
Ravikumar, K. Tetrahedron Lett. 2004, 45, 7231; (b) Raghavan, S.; Naveen
Kumar, Ch. Tetrahedron Lett. 2006, 47, 1585.
There are less than a handful of reports on the stereospecific
transformation of chiral sulfoxides to chiral sulfilimines.11 In an
effort to prepare enantiopure sulfilimines, optically pure (+)-5a12
was reacted with 3a under standard conditions in benzene at
0 °C to rt, only to obtain racemic 6a. Chiral HPLC13 after 30 min
revealed the presence of 20% and 28% yields of (+)- and (ꢀ)-5a,
respectively, along with 17% and 22% yields of enantiomers of 6a.
Chiral HPLC after 1 h revealed the presence of both enantiomers
of 6a in equimolar quantity (32% each) along with enantiomers
of 5a in equal amounts (11% each). It can be inferred that (+)-5a
is epimerized by 3a faster than its reaction with 3a to afford 6a.
The outcome of the reaction (+)-5a with 3a in other solvents such
as dichloromethane, acetonitrile and THF was no better. A mecha-
nism explaining the racemization of (+)-5a by 3a, through the
intermediacy of intermediates III and/or IV, yielding (ꢀ)-5a and
regenerating 3a is depicted in Scheme 3.
In conclusion, we have disclosed a novel method for the prepa-
ration of a variety of sulfilimines with different protecting groups
on the nitrogen, from the corresponding sulfoxides, using the
appropriate Burgess reagent. Efforts to prepare optically active sul-
filimines from optically active sulfoxides met with failure. Studies
are in progress to prepare diastereomeric b-siloxy sulfilimines
from the corresponding sulfoxides and to employ them in
synthesis.
6. Raghavan, S.; Ramakrishna Reddy, S.; Tony, K. A.; Naveen Kumar, Ch.; Nanda, S.
Synlett 2001, 851.
7. Pellissier, H. Tetrahedron 2006, 62, 5559.
8. (a) Atkins, G. M.; Burgess, E. M. J. Am. Chem. Soc. 1968, 90, 4744; (b) McCague, R.
J. Chem. Soc., Perkin Trans. 1 1987, 1011; (c) Stalder, H. Helv. Chim. Acta 1986, 69,
1887; (d) Goldsmith, D. J.; Kezar, H. S. Tetrahedron Lett. 1980, 21, 3543; (e)
Burgess, E. M.; Penton, H. R., Jr.; Taylor, E. A. J. Am. Chem. Soc. 1970, 92, 5224.
9. For the use of the Burgess reagent as a source of heteroatoms in (i) the
conversion of alcohols to urethanes see: (a) Wood, M. R.; Kim, J. Y.; Books, K. M.
Tetrahedron Lett. 2002, 43, 3887; (b) Burgess, E. M.; Penton, H. R., Jr.; Taylor, E.
A. J. Org. Chem. 1973, 38, 26; (c) Atkins, G. M.; Burgess, E. M. J. Am. Chem. Soc.
1972, 94, 6135; (ii) Conversion of epoxides and diols to sulfamidates see: (d)
Rinner, U.; Adams, D. R.; dos Santos, M. L.; Abboud, K. A.; Hudlicky, T. Synlett
2003, 1247; (e) Leisch, H.; Saxon, R.; Sullivan, B.; Hudlicky, T. Synlett 2006, 445;
(f) Nicolaou, K. C.; Huang, X.; Snyder, S. A.; Rao, P. B.; Bella, M.; Reddy, M. V.
Angew. Chem., Int. Ed. 2002, 41, 834; (iii) Conversion of amino alcohols to
sulfamides see (g) Nicolaou, K. C.; Longbottom, D. A.; Snyder, S. A.; Nalbandian,
A. Z.; Huang, X. Angew. Chem., Int. Ed. 2002, 41, 3886; (iv) Epoxy alcohols to
hydroxysulfamidates see: (h) Nicolaou, K. C.; Snyder, S. A.; Longbottom, D. A.;
Nalbandian, A. Z.; Huang, X. Chem. Eur. J. 2004, 10, 5581; (v) Conversion of
thiols to disulfides see: (i) Banfield, S. C.; Omori, A. T.; Leisch, H.; Hudlicky, T. J.
Org. Chem. 2007, 72, 4989.
Acknowledgements
S.R. is thankful to Dr. J. M. Rao, Head, Org. Div. I and Dr. J. S.
Yadav, Director, IICT for constant support and encouragement.
S.M. and K.R. are thankful to the CSIR, New Delhi, for fellowships.
Financial assistance from DST (New Delhi) is gratefully acknow-
ledged. We thank Dr. A. C. Kunwar for the NMR spectra and Dr.
M. Vairamani for the mass spectra.
10. See Electronic Supplementary data.
11. For the preparation of optically active sulfilimines from sulfoxides using N-
sulfinyl-p-toluenesulfonamide see: (a) Yamagishi, F. G.; Rayner, D. R.; Zwicker,
E. T.; Cram, D. J. J. Am. Chem. Soc. 1973, 95, 1916; (b) Christensen, B. W. J. Chem.
Soc. D 1971, 597; (c) Cram, D. J.; Day, J.; Rayner, D. R.; von Schriltz, D. M.;
Duchamp, D. J.; Garwood, D. C. J. Am. Chem. Soc. 1970, 92, 7369; (d) Christensen,
B. W.; Kjaer, A. Chem. Commun. 1969, 934; (e) Johnson, C. R.; Rigau, J. J. J. Org.
Chem. 1968, 33, 4340; (f) Using N,N0-bis(p-toluenesulfonyl)sulfur diimide see:
Ref. 11a; Using p-tosyl isocyanate see: (g) Garwood, D. C.; Jones, M. R.; Cram, D.
J. J. Am. Chem. Soc. 1973, 95, 1925.
Supplementary data
12. Drago, C.; Caggiano, L.; Jackson, R. F. W. Angew. Chem., Int. Ed. 2005, 44, 7221.
13. HPLC column conditions: Eurocel 01 chiral column, eluent: 10% IPA/90%
hexane, flow rate: 1 mL/min.
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2008.04.152.