N-Bromosuccinimide-thiol cobromination in basic medium: an efficient one-pot transformation of olefins into the corresponding enol thioethers

Article abstract of DOI:10.1016/j.tetlet.2007.06.037

A convenient method for the one-pot conversion of olefins into the corresponding enol thioethers is reported. The products were obtained via the N-bromosuccinimide cobromination reaction of olefins with thiols in basic medium. Steric hindrance present in

Full text of DOI:10.1016/j.tetlet.2007.06.037

Tetrahedron Letters 48 (2007) 5645–5647
N-Bromosuccinimide–thiol cobromination in basic medium:
an efficient one-pot transformation of olefins into the
corresponding enol thioethers
H. Zoghlami,a,* I. Chehidi,a M. Romdhani,a M. M. Chaabounib and A. Bakloutia
aLaboratory of Structural Organic Chemistry, Department of Chemistry, Faculty of Sciences of Tunis, El Manar I, 2092 Tunis, Tunisia
bEcole Supe´rieure des Industries Alimentaires, 58 Avenue Alain Savary, 1003 Tunis, Tunisia
Received 8 February 2007; revised 31 May 2007; accepted 7 June 2007
Available online 9 June 2007
Abstract—A convenient method for the one-pot conversion of olefins into the corresponding enol thioethers is reported. The prod-
ucts were obtained via the N-bromosuccinimide cobromination reaction of olefins with thiols in basic medium. Steric hindrance
present in the product alkenes may explain the stereochemistry observed.
ꢀ 2007 Elsevier Ltd. All rights reserved.
Zeigler1 was the first to describe the use of N-bromo-
succinimide (NBS) as an important reagent for allylic
bromination and a radical chain mechanism was later
proposed for its action by Bloomfield in 1944.2 Since,
many papers describing its widespread use as a synthetic
reagent have been published,3 NBS can be considered
simply as a reservoir capable of sustaining a low stea-
dy-state concentration of bromine during a reaction.4
Although the NBS cobromination reactions of alkenes
are widely used in the presence of nucleophiles such as
Fꢀ,5 little work has been published on these reactions
with sulfur-containing nucleophiles.6–10
out affording the corresponding enol thioethers 2a–g.14
The reaction proceeded via an in situ addition–elimina-
tion mechanism according to Scheme 1.
When the starting alkenes used were styrene or tert-
butylethylene, the reaction was stereospecific and affor-
ded E-alkenes exclusively (see Table 1). However, when
the alkenes used were pentene derivatives 2f and 2g, a
mixture of two isomers was observed. In addition, the
DEPT 13C NMR spectrum showed that each of the four
double bonded carbon atoms of the two isomers is
directly linked to a hydrogen atom, indicating the
existence of a mixture of Z and E stereoisomers. The
mechanism proposed is consistent with results reported
for similar reagents by Reddy et al.15 who showed that
alkyne intermediates yielded Z products.
In a previous paper,11 we reported the preparation of
enol thioethers starting from the corresponding enol
ethers.12 We have also prepared b,b0-dibromodithio-
ethers13 via the cobromination reaction of olefins, in the
presence of NBS, with dimercaptoethane. Herein, we
report cobromination, in basic medium, using various
thiols for the synthesis of new enol thioethers.
As shown in Table 1, several enol thioethers could be
easily prepared and the reaction conditions are mild
and efficient.
Inspired by our previous work13 on the cobromination
of olefins using NBS in the presence of dimercapto-
ethane, the one-pot transformation of alkenes with
NBS and various thiols in a basic medium was carried
However, when the alkene used was cyclohexene, the
reaction proceeded differently and allylic sulfides 3a–c
were obtained with no enol thioethers being formed
(see Table 2). The formation of such products is ex-
plained by trans-Br/RS addition followed by 1,2-diaxial
dehydrobromination, and was confirmed by the DEPT
13C NMR spectroscopy which showed that each ethyl-
enic carbon is linked to one hydrogen atom. The lower
yields observed for these products are presumably due
Keywords: Enol thioethers; N-Bromosuccinimide; Cobromination;
Olefins; Z/E isomers.
*
Corresponding author. E-mail: hzogh@yahoo.com
0040-4039/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.06.037

5646
H. Zoghlami et al. / Tetrahedron Letters 48 (2007) 5645–5647
R2 SH
Br+
1
R
R1-CH-CH2-S-R2
Br
1
R-CH=CH2
CH
CH2
+
1
Br
-
DBU
HBr
/
R-CH=CH-S-R2
1
2a-g
Scheme 1.
Table 1. Yields and configurations of enol thioethers 2a–g
5. Review: Rodriguez, J.-P. Synthesis 1993, 1177–1205.
6. Woodgate, P. D.; Lee, H. H.; Rutledge, P. S.; Cambie,
R. C. Synthesis 1977, 462–464.
NBS
2
1
R-CH=CH-S-R2
1
R-SH
R-CH=CH2
+
THF
DBU
7. Cambie, R. C.; Lee, H. H.; Rutledge, P. S.; Woodgate,
P. D. J. Chem. Soc., Perkin Trans. 1 1979, 757–764.
8. Cambie, R. C.; Larsen, D. S.; Rutledge, P. S.; Woodgate,
P. D. J. Chem. Soc., Perkin Trans. 1 1981, 58–63.
9. Cambie, R. C.; Rutledge, P. S.; Strange, G. A.; Woodgate,
P. D. J. Chem. Soc., Perkin Trans. 1 1983, 553–565.
10. Harwood, L. M.; Le Thuillier, G. Tetrahedron 1980, 36,
2483–2487.
11. Chehidi, I.; Zoghlami, H.; Chaabouni, M. M.; Baklouti,
A. Phosphorus, Sulfur Silicon 2006, 181, 2273–2281.
12. Zoghlami, H.; Chehidi, I.; Chaabouni, M. M.; Baklouti,
A. J. Fluorine Chem. 2004, 125, 1887–1892.
1
2a-g
Enol
R1
R2
Z/E
Yield (%)
thioether 2
2a
2b
2c
2d
2e
2f
C(CH3)3 Ph
C(CH3)3 MeO–CO–CH2
0/100 82
0/100 87
Ph
Ph
C6F13–CH2–CH2 0/100 86
C8F17–CH2–CH2 0/100 85
Ph
nC3H7
nC3H7
MeO–CO–CH2
Ph
MeO–CO–CH2
0/100 75
35/65 74
15/85 82
2g
13. Romdhani, Y. M.; Chaabouni, M. M.; Baklouti, A.
Tetrahedron Lett. 2003, 44, 5263–5265.
Table 2. Yields of allylic sulfides 3a–c
14. Preparation of enol thioethers: To a mixture of 0.05 mol of
alkene in THF (50 mL) and NBS (0.05 mol) cooled to 0 ꢁC
were added dropwise, respectively, 0.05 mol of thiol and
0.08 mol of DBU. After complete addition, the mixture
was stirred at room temperature for 4 h, then diluted with
ether (2 · 50 mL) and 2 N sulfuric acid solution was added
until pH ꢁ 5 was reached. The organic phase was washed
with aqueous K2CO3 solution and water, dried over
Na2SO4 and the solvent evaporated. The residue was
purified by silica gel column chromatography using
petroleum ether/dichloromethane as eluent (90:10).
Spectral data for compounds 2a–g and 3a–c: Compound 2a:
Oil; IR (CHCl3): m (cmꢀ1) = 1635 (C@C). 1H NMR
(300 MHz, CDCl3): d (ppm) = 1.05 (s, 9H); 5.96 (d, 1H,
3JHH = 15.46 Hz); 6.11 (d, 1H, 3JHH = 15.46 Hz); 7.26 (m,
5H). 13C NMR (75 MHz, CDCl3): d (ppm) = 30.11
((CH3)3); 34.76 ((CH3)3C); 117.20 (C–CH@); 126.24;
127.40; 128.59; 129.46 (4s, Carom); 148.01 (@CH–S). ESI-
HRMS: M+ calculated 192.0973, found 192.0968, D
(mmu) = 0.5.
SR
NBS
R-SH
+
THF
DBU
3a-c
Allylic sulfide 3
R
Yield (%)
3a
3b
3c
MeO–CO–CH2
C6F13–CH2–CH2
C8F17–CH2–CH2
53
60
62
to the formation of dibromo derivatives as by-prod-
ucts16 which, in this case, are converted to the 3-bromo-
cyclohexene, as identified in the crude product mixture.
In summary, we have reported a one-pot preparation
of novel enol thioethers. This type of enol thioether
is scarcely described in the literature and the extension
of this method to the preparation of substituted
alkenes as well as to naturally occurring compounds
is under investigation.
Compound 2b: Oil; IR (CHCl3): m (cmꢀ1) = 1640 (C@C);
1772 (C@O). 1H NMR (300 MHz, CDCl3): d (ppm) =
1.00 (s, 9H); 3.29 (s, 2H); 3.66 (s, 3H); 5.71 (d, 1H,
3
3JHH = 15.06 Hz); 5.86 (d, 1H, JHH = 15.06 Hz). 13C
NMR (75 MHz, CDCl3): d (ppm) = 29.51 ((CH3)3); 34.26
((CH3)3C); 34.96 (S–CH2); 52.84 (O–CH3); 116.78 (C–
CH@); 144.34 (@CH–S); 170.30 (CO). ESI-HRMS: M+
calculated 188.0871, found 188.0867, D (mmu) = 0.4.
Compound 2c: Oil; IR (CHCl3): m (cmꢀ1) = 1642 (C@C).
1H NMR (300 MHz, CDCl3): d (ppm) = 2.49 (m, 2H);
References and notes
1. Ziegler, K.; Spaeta, A.; Schaaf, E.; Schumann, W.;
Winkelmann, E. Ann. 1942, 551, 80.
2. Bloomfield, F. C. J. Chem. Soc. 1944, 14.
3. See for example: Walling, C.; Rieger, A. L.; Tanner, D. D.
J. Am. Chem. Soc. 1963, 85, 3129–3134, and references
cited therein.
4. Adam, J.; Gosselain, P. A.; Goldfinger, P. Nature 1953,
171, 704; Adam, J.; Gosselain, P. A.; Goldfinger, P. Bull.
Soc. Chim. Belg. 1956, 65, 533.
3
3
2.99 (t, 2H, JHH = 7.1 Hz); 6.49 (d, 1H, JHH
=
3
15.51 Hz); 6.64 (d, 1H, JHH = 15.51 Hz); 7.27 (m, 5H).
13C NMR (75 MHz, CDCl3): d (ppm) = 23.46 (t, CH2–S,
3JCF = 4.35 Hz); 32.07 (t, CF2–CH2, JCF = 22.12 Hz);
2
115.37 (Ph–CH@); 125.81; 127.58; 128.41; 129.63 (4s,
C
arom); 136.60 (s, @CH–S). 19F NMR (282 MHz, CFCl3):
d (ppm) = ꢀ81.65 (m, 3F, CF3); ꢀ115.12 (m, 2F, CF2a);
ꢀ122.43 (m, 2F, CF2b); ꢀ123.63 (m, 2F, CF2c); ꢀ124.92

H. Zoghlami et al. / Tetrahedron Letters 48 (2007) 5645–5647
5647
(m, 2F, CF2d); ꢀ127.11 (m, 2F, CF2x). ESI-HRMS: M+
calculated 482.0374, found 482.0369, D (mmu) = 0.5.
Compound 2d: Oil; IR (CHCl3): m (cmꢀ1) = 1640 (C@C).
1H NMR (300 MHz, CDCl3): d (ppm) = 2.47 (m, 2H);
5.62 (m, 1H, 3JHH(Z) = 7.45 Hz); 5.67 (m, 1H,
3
3JHH(Z) = 7.45 Hz); 5.76 (m, 1H, JHH(E) = 15.42 Hz);
3
5.96 (m, 1H, JHH(E) = 15.42 Hz). 13C NMR (75 MHz,
CDCl3): d (ppm) = 13.44 (CH3); 22.06 (CH2); 30.90
(CH2); 34.85 (S–CH2); 52.28 (OCH3); 120.90; 122.85 (2s,
C–CH@); 131.38; 133.71 (2s, @CH–S); 170.18 (s, CO).
ESI-HRMS: M+ calculated 174.0715, found 174.0713, D
(mmu) = 0.2.
3
3
3.01 (t, 2H, JHH = 7.1 Hz); 6.52 (d, 1H, JHH
=
3
15.45 Hz); 6.67 (d, 1H, JHH = 15.45 Hz); 7.25 (m, 5H).
13C NMR (75 MHz, CDCl3): d (ppm) = 23.49 (t, CH2–S,
2
3JCF = 4.33 Hz); 32.06 (t, CF2–CH2, JCF = 22.18 Hz);
115.33 (s, Ph–CH@); 125.86; 127.58; 128.41; 129.67 (4s,
Compound 3a: Oil; IR (CHCl3): m (cmꢀ1) = 1640 (C@C);
C
arom); 136.55 (s, @CH–S). 19F NMR (282 MHz, CFCl3):
1770 (C@O). 1H NMR (300 MHz, CDCl3):
d
d (ppm) = ꢀ81.63 (m, 3F, CF3); ꢀ115.02 (m, 2F, CF2a);
ꢀ122.50 (m, 2F, CF2b); ꢀ123.52 (m, 4F, 2 CF2c); ꢀ124.07
(m, 2F, CF2d); ꢀ124.94 (m, 2F, CF2x); ꢀ127.03 (m, 2F,
CF2v). ESI-HRMS: M+ calculated 582.0310, found
582.0304, D (mmu) = 0.6.
(ppm) = 1.28–2.29 (m, 6H); 3.12 (m, 1H); 3.33 (s, 2H);
3.71 (s, 3H); 5.62 (m, 2H). 13C NMR (75 MHz, CDCl3): d
(ppm) = 29.62–30.46 ((CH2)4); 34.91 (S–CH2); 52.74 (O–
CH3); 117.11 (CH = C); 144.41 (@C–S); 170.47 (CO). ESI-
HRMS: M+ calculated 186.0715, found 186.0711, D
(mmu) = 0.4.
Compound 2e: Oil; IR (CHCl3): m (cmꢀ1) = 1645(C@C);
1765 (C@O). 1H NMR (300 MHz, CDCl3): d (ppm) =
Compound 3b: Mp = 65 ꢁC; IR (CHCl3): m (cmꢀ1) = 1645
(C@C). 1H NMR (300 MHz, CDCl3): d (ppm) = 1.32–
3
3.34 (s, 2H); 3.69 (s, 3H); 6.57 (d, 1H, JHH = 15.32 Hz);
3
3
6.73 (d, 1H, JHH = 15.32 Hz); 7.41 (m, 5H). 13C NMR
2.28 (m, 6H); 2.44 (m, 2H); 3.05 (t, 2H, JHH = 7.3 Hz);
(75 MHz, CDCl3): d (ppm) = 34.96 (S–CH2); 52.79 (O–
CH3); 117.01 (Ph–CH@); 126.02; 127.61; 128.42; 129.61
(4s, Carom); 144.36 (s, @CH–S); 170.52 (s, CO). ESI-
HRMS: M+ calculated 208.0558, found 208.0554, D
(mmu) = 0.4.
3.17 (m, 1H); 5.59 (m, 2H). 13C NMR (75 MHz, CDCl3): d
3
(ppm) = 23.51 (t, CH2–S, JCF = 4.41 Hz); 29.58–30.52
2
(m, (CH2)4); 32.04 (t, CF2–CH2, JCF = 22.32 Hz); 115.34
(s, CH@C); 136.67 (s, @C–S). 19F NMR (282 MHz,
CFCl3): d (ppm) = ꢀ81.69 (m, 3F, CF3); ꢀ115.18 (m, 2F,
CF2a); ꢀ122.48 (m, 2F, CF2b); ꢀ123.59 (m, 2F, CF2c);
ꢀ125.02 (m, 2F, CF2d); ꢀ127.07 (m, 2F, CF2x). ESI-
HRMS: M+ calculated 460.0530, found 460.0523, D
(mmu) = 0.7.
Compound 2f: Mp = 78 ꢁC; IR (CHCl3): m (cmꢀ1) =
1642 (C@C). 1H NMR (300 MHz, CDCl3): d (ppm) =
0.93 (m, 6H: due to overlap of the signals of the Z and E
isomers); 1.44 (m, 4H: due to overlap of the signals of the
Z and E isomers); 2.12 (m, 2H); 2.23 (m, 2H); 5.75 (m, 1H,
Compound 3c: Mp = 69 ꢁC; IR (CHCl3):m (cmꢀ1) = 1646
(C@C). 1H NMR (300 MHz, CDCl3): d (ppm) = 1.31–
3
3JHH(Z) = 7.36 Hz); 5.90 (m, 1H, JHH(Z) = 7.36 Hz); 6.00
3
(m,
1H,
3JHH(E) = 15.23 Hz);
6.20
(m,
1H,
2.25 (m, 6H); 2.47 (m, 2H); 3.02 (t, 2H, JHH = 7.2 Hz);
3JHH(E) = 15.23 Hz); 7.31 (m, 10H: due to overlap of the
signals of the Z and E isomers). 13C NMR (75 MHz,
CDCl3): d (ppm) = 13.86; 14.00 (2s, CH3); 22.45; 22.53
(2s, CH2); 31.37; 35.35 (2s, CH2–CH@); 121.20; 123.07
(2s, C–CH@); 133.65; 137.56 (2s, @CH–S); 126.19–129.26
(m, Carom). ESI-HRMS: M+ calculated 178.0816, found
178.0813, D (mmu) = 0.3.
3.17 (m, 1H); 5.63 (m, 2H). 13C NMR (75 MHz, CDCl3): d
3
(ppm) = 23.49 (t, CH2–S, JCF = 4.33 Hz); 29.54–30.56
2
(m, (CH2)4); 32.06 (t, CF2–CH2, JCF = 22.18 Hz); 115.33
(s, CH@C); 136.55 (s, @C–S). 19F NMR (282 MHz,
CFCl3): d (ppm) = ꢀ81.52 (m, 3F, CF3); ꢀ114.96 (m, 2F,
CF2a); ꢀ122.44 (m, 2F, CF2b); ꢀ123.54 (m, 4F, 2 CF2c);
ꢀ123.96 (m, 2F, CF2d); ꢀ124.92 (m, 2F, CF2x); ꢀ126.96
(m, 2F, CF2v). ESI-HRMS: M+ calculated 560.0467,
found 560.0462, D (mmu) = 0.5.
Compound 2g: Mp = 78 ꢁC; IR (CHCl3): m (cmꢀ1) = 1638
(C@C); 1764 (C@O). 1H NMR (300 MHz, CDCl3): d
(ppm) = 0.90 (t, 6H: due to overlap of the signals of the Z
15. Reddy, M. V. R.; Mallireddigari, M. R.; Pallela, V. R.;
Venkatapuram, P.; Roominathan, R.; Bell, S. C.; Reddy,
E. P. Bioorg. Med. Chem. 2005, 13, 1715.
16. Camps, F.; Chamorro, E.; Gasol, V.; Guerrero, A. J. Org.
Chem. 1989, 54, 4294–4298.
3
and E isomers, JHH = 7.43 Hz); 1.41 (m, 4H: due to
overlap of Z and E isomers); 2.07 (m, 4H: due to overlap
of Z and E isomers); 3.35 (s, 4H: due to overlap of Z and E
isomers); 3.73 (s, 6H: due to overlap of Z and E isomers);