Synthesis of lithium 1-alkynesulfenates by the mild oxidation of thiolates with a pinacolone-derived N-sulfonyloxaziridine

Article abstract of DOI:10.1055/s-2006-951552

Lithium 1-alkynethiolates, generated by a base-induced ring cleavage of 4-substituted 1,2,3-thiadiazoles, were efficiently converted into the corresponding sulfenate salts by mild oxidation using an N-sulfonyloxaziridine derived from pinacolone. In situ S

Full text of DOI:10.1055/s-2006-951552

LETTER
3289
Synthesis of Lithium 1-Alkynesulfenates by the Mild Oxidation of Thiolates
with a Pinacolone-Derived N-Sulfonyloxaziridine
Synthesis of
L
r
ithium
1
a
-Alkynesul
n
f
enates ck Sandrinelli,a Cédric Boudou,a Caroline Caupène,a Marie-Thérèse Averbuch-Pouchot,b Stéphane Perrio,*a
Patrick Metznera
a
Laboratoire de Chimie Moléculaire et Thio-Organique (UMR CNRS 6507), ENSICAEN, Université de Caen-Basse Normandie,
6 Boulevard du Maréchal Juin, 14050 Caen, France
Fax +33(23145)2877; E-mail: perrio@ensicaen.fr
b
LEDSS (UMR CNRS 5616), Université Joseph Fourier, BP 53, 38041 Grenoble 9, France
Received 2 August 2006
species conjugated with a triple bond have never been
Abstract: Lithium 1-alkynethiolates, generated by a base-induced
mentioned in the literature, even with recent contributions
ring cleavage of 4-substituted 1,2,3-thiadiazoles, were efficiently
in the area.1,4 As a consequence, no information is given
converted into the corresponding sulfenate salts by mild oxidation
using an N-sulfonyloxaziridine derived from pinacolone. In situ S-
about stability5 and reactivity towards an electrophile. The
alkylation with alkyl halides led to a,b-acetylenic sulfoxides.
more obvious choice for the thiolate precursor would be
the corresponding acetylenic mercaptan. However these
compounds can’t be isolated because of spontaneous
conversion into thioketenes.6 Other alternative routes
include the reaction of an acetylenic lithium reagent with
elemental sulfur or deprotection of 1-(trimethylsilylsulfa-
nyl)alkyne.7 However, both of these methods suffer from
at least one major limitation including generation of side
products or air sensitivity of the precursors. Finally, 1,2,3-
thiadiazoles (3), unsubstituted at the 5-position, seemed to
be ideally suited to our purposes for the following rea-
sons: (i) they are stable heterocycles, readily available in
two steps from the appropriate methyl ketone via a
hydrazone8 (ii) upon treatment with a strong base such as
organolithium reagents, sodamide, sodium hydride and
potassium tert-butoxide, hydrogen abstraction leads to a
carbanion which collapses efficiently to liberate the antic-
ipated 1-alkynethiolate (Scheme 2).9 An attractive feature
of this method is the clean generation of a thiolate in solu-
tion at –78 °C with evolution of gaseous molecules (meth-
ane when using methyllithium as the initial base and
dinitrogen as a result of the heterocyclic ring cleavage).
We wish to present in this Letter the results obtained using
this oxidation approach. In addition, novel and improved
conditions for the synthesis of oxidant 1 will be described.
Key words: oxidation reaction, sulfoxide, sulfenate salt, oxaziri-
dine, heterocycle
Sulfenate salts (RSO–) are not common sulfur nucleo-
philes used by organic chemists, primarily because there
is a lack of efficient methods to generate them.1 However,
these anions are very attractive as precursors of sulfenic
acids, sulfoxides, sulfenate esters and sulfenamides. Fur-
thermore, interest in sulfenates has recently been height-
ened by their identification as key intermediates in some
bioorganic transformations.1
In the course of our work, concerning the reactivity of
thiolates with N-sulfonyloxaziridines,2 we have previous-
ly reported an original and efficient access to lithium
arenesulfenates and identified the pinacolone derivative 1
as an appropriate oxidizing agent (Scheme 1).2a Treat-
ment in situ with aliphatic halides led to aromatic sulfox-
ides in good to excellent yields. Application of the
methodology to enethiolates prepared from dithioesters
was also successful, thus affording an original method in
the formation of ketene dithioacetal S-oxides.2d
1. n-BuLi
3. RX
ArS(O)R
ArSH
ArSOLi
..
2.
R1
O
t-Bu
Me
N
N
1. MeLi
3. R2X
SO2Ph
R1
S(O)R2
R1
SOLi
N
1
2. 1
S
3
2
Scheme 1 Lithium arenesulfenates from thiophenols
R1 = t-Bu (a), Ph (b), Me (c)
Scheme 2 Lithium 1-alkynylsulfenates from 1,2,3-thiadiazoles
These results suggested to us that 1-alkynesulfenates
could, in principle, be available by oxidation of the corre-
sponding acetylenic thiolates (Scheme 2). After reaction
with an alkyl halide, 1-alkynyl alkyl sulfoxides (2) should
be isolated.3 To the best of our knowledge, sulfenate
The required 4-substituted 1,2,3-thiadiazoles 3 were pre-
pared according to protocols previously described in the
literature. Treatment of the appropriate ketone with ethyl
carbazate9a,10 furnished the corresponding hydrazone11 in
quantitative yield. Conversion into the required heterocy-
cle was then achieved through a Hurd–Mori12 reaction
upon treatment with neat thionyl chloride (10 equiva-
lents). Excellent yields of 89% and 83% respectively were
SYNLETT 2006, No. 19, pp 3289–3293
0
1
.1
2
.2
0
0
6
Advanced online publication: 23.11.2006
DOI: 10.1055/s-2006-951552; Art ID: D23506ST
© Georg Thieme Verlag Stuttgart · New York

3290
F. Sandrinelli et al.
LETTER
obtained for the synthesis of the tert-butyl and phenyl de-
rivatives 3a and 3b.13 The synthesis of the methyl target
3c14 was more problematic with the unexpected formation
of 5-chloro-4-methyl-1,2,3-thiadiazole (ratio 85:15),
probably due to an in situ halogenation of the starting hy-
drazone.15 Separation of the products was then achieved
by careful column chromatography (3c was highly vola-
tile) on silica gel using an 85:15 mixture of pentane–dieth-
yl ether as eluent to afford 3c and 4 in 43% and 8% yields,
respectively. No improvement was observed when start-
ing from the analogous tosyl hydrazone instead.16
Figure 1 ORTEP diagram of N-sulfonyloxaziridine (1) (H atoms
not shown)
We have previously reported the synthesis of oxaziridine
1 which involved heating to reflux equimolar amounts of
pinacolone, benzenesulfonamide and titanium tetrachlo-
ride in 1,1,2-trichloroethane for 14 hours. The resulting N-
sulfonylimine was then oxidised using pure m-chloroper-
oxybenzoic acid (MCPBA) in a dichloromethane–water
biphasic medium buffered with sodium carbonate.2a Al-
though the synthesis was chemically efficient, it suffered
globally from some drawbacks, including a problem with
reproducibility and also the need for large amounts of sol-
vent when scaling up reactions. After screening various
conditions for both steps, the most convenient synthesis
was chosen and is described in Scheme 3.17 Condensation
of benzenesulfonamide with two equivalents of pinacolo-
ne and three equivalents of Ti(OEt)4 in refluxing toluene
for 20 hours, followed by treatment with 2 M aqueous so-
dium hydroxide solution to precipitate the titanium oxides
gave the imine in 75% crude yield.18 Further purification
was not required. Oxidation with the 1:2 MCPBA–KF
system initially devised by Camps19 (1.5 equivalents) in
dichloromethane at room temperature led to crystalline
oxaziridine 1 in 84% yield,20 which if necessary could be
recrystallized from hexane.21 A single geometric isomer
was produced and the trans geometry initially assigned on
the basis of spectral data was confirmed by an X-ray struc-
ture (Figure 1).22
and NMR analysis, the crude product was purified by col-
umn chromatography on silica gel. The results obtained
are shown in Table 1. The anticipated sulfoxides 2a, pos-
sessing a t-Bu group on the alkyne moiety, were obtained
in 58–85% yields with the four halides employed (entries
1–4). Examination of the crude product revealed the ab-
sence of the sulfenic ester, which might arise through a
competing O-alkylation of the ambident sulfenate.23 Us-
ing 4-phenylthiadiazole (3b) and benzyl bromide, the sul-
foxide 2b1 was isolated in 50% yield (entry 5). A more
disappointing result (17% yield) was obtained using ethyl
iodide as an alternative quench (entry 6). The sulfoxide
2b2 produced is highly unstable and decomposition is ob-
served even on storage in the fridge. Finally, only trace
amounts of 2c were obtained with the methyl derivative
(entry 7).24
Table 1 1-Alkynyl Alkyl Sulfoxides via Sulfenates According to
Scheme 225
Entry Substrate R1
R2Xa
BnBr
EtI
Product Yield (%)b
1
2
3
4
5
6
7
3a
3a
3a
3a
3b
3b
3c
t-Bu
t-Bu
t-Bu
t-Bu
Ph
2a1
2a2
2a3
2a4
2b1
2b2
2c
77
58
85
75
50
17
<5
MeI
t-Bu
N
c
a, b
SO2Ph
PhSO2NH2
1
BrCH2CO2Et
BnBr
EtI
Me
4
Scheme 3 Synthesis of N-sulfonyloxaziridine (1). Reagents and
conditions: (a) t-BuC(O)Me (2 equiv), Ti(OEt)4 (3 equiv), toluene, re-
flux, 20 h, 75%; (b) 2 M NaOH–H2O; (c) commercial MCPBA (1.5
equiv), KF (3 equiv), CH2Cl2, 0 °C to r.t., 12 h, 71%.
Ph
Me
MeI
a BnBr, BrCH2CO2Et (1.1 equiv), MeI (3 equiv) and EtI (5 equiv).
Before testing our overall sequence, we first checked the b Isolated yields.
efficiency of the thiolate generation with three precursors
we had in hand. Deprotonation using methyllithium in tet-
In conclusion, we have shown that our methodology for
rahydrofuran at –78 °C, the reaction with methyl iodide
and subsequent hydrolysis at the same temperature gave
the anticipated 1-alkynyl methyl thioethers in yields
above 87%.
the oxidation of anionic sulfur centers using the pinacolo-
ne-derived N-sulfonyloxaziridine (1) can be successfully
extended using acetylenic thiolates as substrates, thus pro-
viding an unprecedented access to 1-alkynylsulfenates
under mild conditions. Subsequent S-alkylation with an
alkyl halide affords 1-alkynyl alkyl sulfoxides. This
chemistry nicely complements classical methods for the
synthesis of this class of compounds, consisting of sulfide
oxidation and Andersen-type reactions.24,26 Future work
The transient lithium thiolates generated under the previ-
ous conditions were then treated at –78 °C with one equiv-
alent of N-sulfonyloxaziridine (1). Various electrophiles
were added to trap the eventual sulfenate anion produced.
After hydrolysis with saturated brine solution, work-up
Synlett 2006, No. 19, 3289–3293 © Thieme Stuttgart · New York

LETTER
Synthesis of Lithium 1-Alkynesulfenates
3291
Platts, J. A.; Ruda, A. M.; Tomkinson, N. C. O. Tetrahedron
2006, 62, 410.
will seek to broaden the unique reactivity of oxaziridine 1
to other substrates and to develop further applications of
sulfenic acid anions in organic synthesis.
(12) (a) Hurd, C. D.; Mori, R. I. J. Am. Chem. Soc. 1955, 77,
5359. (b) Fujita, M.; Kobori, T.; Hiyama, T.; Kondo, K.
Heterocycles 1993, 36, 33. (c) Stanetty, P.; Turner, M.;
Mihovilovic, M. D. In Targets in Heterocyclic Systems, Vol.
3; Attanasi, O. A.; Spinelli, D., Eds.; Società Chimica
Italiana: Rome, 1999, 265. (d) Hu, Y.; Baudart, S.; Porco, J.
A. Jr. J. Org. Chem. 1999, 64, 1049. (e) Attanasi, O. A.; De
Crescentini, L.; Filippone, P.; Mantellini, F. Synlett 2001,
557. (f) Thomas, E. W.; Nishizawa, E. E.; Zimmermann, D.
C.; Williams, D. J. J. Med. Chem. 1985, 28, 442.
(g) Kobori, T.; Fujita, M.; Hiyama, T.; Kondo, K. Synlett
1992, 95.
Acknowledgment
We acknowledge financial support from the ‘Ministère de la Re-
cherche’, CNRS (Centre National de la Recherche Scientifique), the
‘Région Basse-Normandie’ and the European Union (FEDER fun-
ding). We also thank Marco Greb, Anne Vanderperre and Christo-
phe Duplay for synthesis of starting materials.
(13) 4-(1,1-Dimethylethyl)-1,2,3-thiadiazole (3a):27a R1 = t-Bu;
beige powder, (89%); mp 23 °C (Lit.27a 23 °C); 1H NMR
(250 MHz, CDCl3): d = 1.51 (s, 9 H), 8.15 (s, 1 H); 13C NMR
(62.9 MHz, CDCl3): d = 30.9, 34.0, 129.3, 173.6; IR (NaCl):
2964, 2870, 1490, 1462, 1244, 964, 890 cm–1; MS (EI): m/z
(%) = 142 (11) [M+], 57 (100), 43 (97), 41 (98).
References and Notes
(1) For a recent review including chemical and biological
aspects of sulfenates, see: O’Donnell, J. S.; Schwan, A. L. J.
Sulfur Chem. 2004, 25, 183.
(2) (a) Sandrinelli, F.; Perrio, S.; Beslin, P. J. Org. Chem. 1997,
62, 8626. (b) Sandrinelli, F.; Perrio, S.; Beslin, P. Org. Lett.
1999, 1, 1177. (c) Sandrinelli, F.; Perrio, S.; Averbuch-
Pouchot, M.-T. Org. Lett. 2002, 4, 3619. (d) Sandrinelli, F.;
Fontaine, G.; Perrio, S.; Beslin, P. J. Org. Chem. 2004, 69,
6916. (e) Martin, C.; Sandrinelli, F.; Perrio, C.; Perrio, S.;
Lasne, M.-C. J. Org. Chem. 2006, 71, 210.
(3) Examples of alkynyl alkyl sulfoxides are scarce, in contrast
to alkynyl aryl derivatives. One reason is probably a relative
instability. For example, polymerization upon standing or
decomposition with a vigorous evolution of gas has been
mentioned: (a) Russel, G. L.; Ochrymowycz, L. A. J. Org.
Chem. 1970, 35, 2106. (b) Truce, W. E.; Lusch, M. J. J. Org.
Chem. 1978, 43, 2252.
(4) The most relevant alternative routes to sulfenates are the
oxidative cleavage of 1-alkynyl sulfoxides using a Pd(0)
catalyst followed by transmetallation with Et2Zn, an
addition/elimination methodology with b-sulfinylacrylates
and a retro-Michael reaction initiated by a base from b-
sulfinylesters. See ref. 1 and: Caupène, C.; Boudou, C.;
Perrio, S.; Metzner, P. J. Org. Chem. 2005, 70, 2812.
(5) The analogous sulfur anion with a higher oxidation
state(sulfinate) readily decomposes with SO2 evolution:
Carpino, L. A.; Rynbrandt, R. H. J. Am. Chem. Soc. 1966,
88, 5682.
4-Phenyl-1,2,3-thiadiazole (3b):27b R1 = Ph; orange solid
recrystallized from n-hexane (83%); mp 76–78 °C (Lit.27b
77–78 °C); 1H NMR (250 MHz, CDCl3): d 7.41–7.55 (m, 3
H), 8.02–8.07 (m, 2 H), 8.65 (s, 1 H); 13C NMR (62.9 MHz,
CDCl3): d = 127.8, 129.6, 129.9, 130.4, 131.2, 163.3; IR
(NaCl): 3072, 1462, 1442, 1220, 766, 692 cm–1; MS (EI):
m/z (%) = 162 (6) [M+], 134 (100), 90 (18).
(14) 4-Methyl-1,2,3-thiadiazole (3c):27c R1 = Me; white solid
which melted rapidly at r.t. (43%); 1H NMR (250 MHz,
CDCl3): d = 2.81 (s, 3 H), 8.17 (s, 1 H); 13C NMR (62.9
MHz, CDCl3): d = 13.93, 132.6, 160.0; IR (NaCl): 3104,
1494, 1444, 1224 cm–1; MS (CI): m/z (%) = 101 (100) [M +
H+], 71 (79).
(15) 5-Chloro-4-methyl-1,2,3-thiadiazole: Orange oil (8%);
1H NMR (250 MHz, CDCl3): d = 2.7 (s, 3 H); MS (CI): m/z
(%) = 135 (100) [M + H+] 35Cl, 137 (35) [M + H+] 37Cl, 71
(50).
(16) Wu, P.-L.; Peng, S.-Y.; Magrath, J. Synthesis 1996, 249.
(17) N-(1,2,2-Trimethylpropylidene)benzenesulfonamide (4).
To a mixture of pinacolone (9.1 mL, 73 mmol) and
benzenesulfonamide (5.8 g, 36.5 mmol) in toluene (360
mL), Ti(OEt)4 (25 g, 110 mmol) was added dropwise while
stirring. The reaction mixture was slowly heated to reflux
(oil bath temperature at 115 °C). After refluxing for 20 h, the
yellow mixture was cooled to r.t. and an aq NaOH solution
(0.5 M, 350 mL) was added slowly. The white gel of
titanium oxides formed was filtered through celite to give a
biphasic filtrate. The organic phase was separated and the aq
layer extracted with Et2O (2 × 150 mL). The combined
organic extracts were washed with sat. aq NaCl solution
(100 mL) and dried over MgSO4. Filtration and concen-
tration under reduced pressure led to imine 4 (6.5 g, 27
mmol, 75%) as a yellowish solid. The product was used
without further purification.
(18) Imine 4 was also prepared in good yield (70–80%) by a free
radical rearrangement of O-sulfinyl oximes (Hudson
reaction) prepared by the reaction of pinacolone oxime with
benzenesulfinyl chloride in the presence of triethylamine.
Purification of the crude material is essential: Brown, C.;
Hudson, R. F.; Record, K. A. F. J. Chem. Soc., Perkin Trans.
2 1977, 822.
(6) D’hooge, B.; Smeets, S.; Toppet, S.; Dehaen, W. Chem.
Commun. 1997, 1753.
(7) (a) Brandsma, L.; Zwikker, J. W.; Bilthoven, N. Product
Subclass 11: Lithium Alkynolates, Alkanethiolates and
Alkyneselenolates, In Science of Synthesis, Vol. 8a;
Snieckus, V., Ed.; Georg Thieme Verlag: Stuttgart, 2006,
305. (b) Sukhai, R. S.; Meijer, J.; Brandsma, L. Recl. Trav.
Chim. Pays-Bas 1977, 96, 79.
(8) Wilkins, D. J.; Bradley, P. A. Product Class 9: 1,2,3-
Thiadiazoles, In Science of Synthesis, Vol. 13; Storr, R. C.;
Gilchrist, T. L., Eds.; Georg Thieme Verlag: Stuttgart, 2004,
253.
(9) (a) Raap, R.; Micetich, R. G. Can. J. Chem. 1968, 46, 1057.
(b) Schaumann, E.; Grabley, F.-F. Liebigs Ann. Chem. 1979,
1746.
(10) Al-Masoudi, N.; Hassan, N. A.; Al-Soud, Y. A.; Schmidt, P.;
Gaafar, A. E.-DM.; Weng, M.; Marino, S.; Schoch, A.;
Amer, A.; Jochims, J. C. J. Chem. Soc., Perkin Trans. 1
1998, 947.
(19) Camps, F.; Coll, J.; Messeguer, A.; Pujol, F. J. Org. Chem.
1982, 47, 5402.
(20) trans-3-(1,1-Dimethylethyl)-3-methyl-2-(phenyl-
sulfonyl)oxaziridine (1). KF (8.5 g, 146.8 mmol) was
dried by heating at 120 °C for 2 h under reduced pressure (1
Torr) and a solution of commercial MCPBA (70%, 18 g,
(11) The hydrazones were fully characterized and the data
collected were in agreement with those previously reported:
(a) Rabjohn, N.; Barnstorff, H. D. J. Am. Chem. Soc. 1953,
75, 2259. (b) Al-Smadi, M.; Ratrout, S. Molecules 2004, 9,
957. (c) Cavill, J. L.; Elliott, R. L.; Evans, G.; Jones, I. L.;
Synlett 2006, No. 19, 3289–3293 © Thieme Stuttgart · New York

3292
F. Sandrinelli et al.
LETTER
concentration under reduced pressure, the residue was
purified by column chromatography (PE–EtOAc mixtures)
to give the anticipated sulfoxides 2.
1-Benzylsulfinyl-3,3-dimethylbut-1-yne (2a1): Obtained
from thiadiazole 3a (R1 = t-Bu, 142 mg, 1 mmol) using
benzyl bromide (R2 = Bn, 130 mL, 1.1 mmol) as the
electrophile gave 2a1 as a colorless oil (170 mg, 0.77 mmol,
77%); Rf = 0.19 (PE–EtOAc, 4:1); 1H NMR (250 MHz,
CDCl3): d = 1.22 (s, 9 H), 4.25 (s, 2 H), 7.35–7.37 (m, 5 H);
13C NMR (62.9 MHz, CDCl3): d = 28.8, 30.3, 63.1, 75.8,
113.9, 129.0, 129.1, 129.6, 130.9; IR (NaCl) 3032, 2972,
2928, 2868, 2160 (C≡C), 1454, 1252, 1060 cm–1; MS (EI):
m/z (%) = 220 (1) [M+], 91 (100), 65 (14); Anal. Calcd for
C13H16OS: C, 70.87; H, 7.32; S, 14.55. Found: C, 70.75; H,
7.47; S, 14.76.
73.4 mmol) in CH2Cl2 (300 mL) previously dried over
MgSO4 was added. A solution of crude imine 4 (11.7 g, 48.9
mmol) was added and the resulting white suspension was
stirred at 0 °C for 3 h and then for a further 12 h at r.t. After
filtration to remove the insoluble materials and concen-
tration, the residue was filtered through SiO2 with CH2Cl2 as
eluent to afford oxaziridine 1 (8.77 g, 34.4 mmol, 71%).
(21) Various oxidizing agents were tested using successful
experimental conditions reported in the synthesis of other
N-sulfonyloxaziridines. However, most of them gave very
disappointing results with, for example, no reaction taking
place using Oxone® and formation of hydrolysis products
using H2O2: (a) Davis, F. A.; Chattopadhyay, S.; Towson, J.
C.; Lal, S.; Reddy, T. J. Org. Chem. 1988, 53, 2087.
(b) Page, P. C. B.; Heer, J. P.; Bethell, D.; Lund, A.;
Collington, E. W.; Andrews, D. M. J. Org. Chem. 1997, 62,
6093.
(22) Crystal-structure determination of 1: Single crystals of
oxaziridine 1, suitable for X-ray crystallographic analysis,
were obtained by slow evaporation of n-hexane. X-ray
diffraction experiments for the monocrystal of 1 were
performed at 293.2 K with graphite-monochromatized Mo
Ka radiation on an Enraf–Nonius CAD–4 diffractometer.
Formula C12H17NO3S, formula weight 255, crystal system
triclinic, space group P–1 (n° 2), a = 9.013 (1) Å, b = 9.169
(4) Å, c = 9.528 (3) Å, a = 108.39 (3)°, b = 108.38 (2)°,
g = 70.09 (2)°, V = 683.2 (4) Å3, Z = 2, density calcd = 1.24
g/cm3, m = 2.3 cm–1, R = 0.034, wR = 0.0515. Selected bond
lengths (Å) and angles (°): O1–C1 1.422 (1), O1–N1 1.484
(1), N1–C1 1.450 (2), S1–N1 1.704 (1), S1–O3 1.421 (1),
S1–C7 1.750 (1), C7–C12 1.371 (2), C7–C8 1.374 (2), C1–
C2 1.500(2), C1–C3 1.527 (2), C3–C6 1.536 (2), N1–O1–C1
59.90 (7), N1–O1–C1 57.84 (7), O1–C1–N1 62.19 (7), S1–
N1–C1 120.27 (9), O2–S1–O3 120.03 (7), O2–S1–N1
102.29 (6), O3–S1–N1 114.31 (6), S1–N1–C1 120.27 (9).
Data reduction: TEXSAN (Molecular Structure
Corporation). Program(s) used to solve structure: SIR92.
Program(s) used to refine structure: TEXSAN. Software
used to prepare material for publication: TEXSAN.
Crystallographic data for compound 1 have been deposited
at the Cambridge Crystallographic Data Centre, CCDC No
615446. Copies of this information may be obtained free of
charge from The Director, CCDC, 12 Union Road,
Cambridge, CB2 1EZ, UK; +44 (1223)336408; E-mail:
deposit@ccdc.cam.ac.uk or http://www.ccdc.cam.ac.uk.
(23) (a) Hogg, D. R.; Robertson, A. J. Chem. Soc., Perkin Trans.
1 1979, 1125. (b) Kobayashi, M.; Toriyabe, K. Sulfur Lett.
1985, 3, 117.
1-Ethylsulfinyl-3,3-dimethylbut-1-yne (2a2). Obtained
from thiadiazole 3a (R1 = t-Bu, 142 mg, 1 mmol) using ethyl
iodide (R2 = Et, 0.4 mL, 5 mmol) as the electrophile gave 2a2
as a colorless oil (92 mg, 0,58 mmol, 58%); (Rf = 0.3 (PE–
EtOAc, 4:1); 1H NMR (250 MHz, CDCl3): d = 1.29 (s, 9 H),
1.42 (t, J = 7.4 Hz, 3 H), 2.98 and 3.06 (AB part of ABX3,
J
AB = 13 Hz, JAX = JBX = 7.4 Hz, 2 H); 13C NMR (62.9 MHz,
CDCl3): d = 6.8, 28.8, 30.4, 50.5, 75.7, 112.6; IR (NaCl):
2972, 2932, 2870, 2160 (C≡C), 1456, 1252, 1070 cm–1; MS
(EI): m/z (%) = 158 (47) [M+], 142 (33), 130 (68), 115 (100);
HRMS m/z calcd for C8H14OS: 158.0765; found: 158.0769.
3,3-Dimethyl-1-methylsulfinylbut-1-yne (2a3). Obtained
from thiadiazole 3a (R1 = t-Bu, 142 mg, 1 mmol) using
methyl iodide (R2 = Me, 186 mL, 3 mmol) as the electrophile
gave 2a3 as a pale pink oil (123 mg, 0,85 mmol, 85%);
Rf = 0.32 (PE–EtOAc, 1:1); 1H NMR (250 MHz, CDCl3):
d = 1.29 (s, 9 H), 2.92 (s, 3 H); 13C NMR (62.9 MHz,
CDCl3): d = 28.8, 30.4, 44.1, 77.7, 112.1; IR (NaCl): 2972,
2930, 2870, 2158 (C≡C), 1456, 1252, 1070 cm–1; MS (EI):
m/z (%) = 144 (100) [M+], 129 (22), 113 (25), 81 (42);
HRMS m/z calcd for C7H12OS: 144.0608; found: 144.0611.
(3,3-Dimethylbut-1-ynylsulfinyl)acetic acid ethyl ester
(2a4). Obtained from thiadiazole 3a (R1 = t-Bu, 142 mg, 1
mmol) using 2-bromoacetic acid ethyl ester (R2 =
CH2CO2Et, 0.12 mL, 1.1 mmol) as the electrophile gave 2a4
as a colorless oil (162 mg, 0.75 mmol, 75%); Rf = 0.21 (PE–
EtOAc, 4:1); 1H NMR (250 MHz, CDCl3): d = 1.29 (s, 9 H),
1.32 (t, J = 7.1 Hz, 3 H), 3.92 and 4.08 (AB, J = 13.6 Hz, 2
H), 4.26 (q, J = 7.1 Hz, 2 H); 13C NMR (62.9 MHz, CDCl3):
d = 14.5, 29.0, 30.3, 61.4, 62.6, 75.7, 114.0, 164.6; IR
(NaCl): 2974, 2932, 2870, 2160 (C≡C), 1740 (C=O), 1456,
1366, 1252, 1070 cm–1; MS (EI): m/z (%) = 216 (35) [M+],
201 (62), 173 (80), 113 (36), 67 (38), 59 (48), 43 (100); Anal.
Calcd for C10H16O3S: C, 55.53; H, 7.46; S, 14.82. Found: C,
55.63; H, 7.46; S, 14,52.
1-Benzylsulfinyl-2-phenylacetylene (2b1). Obtained from
thiadiazole 3b (R1 = Ph, 162 mg, 1 mmol) using benzyl
bromide (R2 = Bn, 0.130 mL, 1.1 mmol) as the electrophile
gave 2b1 as an orange oil which needed to be purified
quickly on SiO2 and stored in a fridge (120 mg, 0.50 mmol,
50%); Rf = 0.30 (PE–EtOAc, 4:1); 1H NMR (250 MHz,
CDCl3): d = 4.39 (pseudo s, 2 H), 7.35–7.46 (m, 10 H);
13C NMR (62.9 MHz, CDCl3): d = 63.1, 85.4, 103.7, 120.1,
128.7, 129.0, 129.1, 129.2, 129.4, 131.0, 132.6; IR (NaCl):
3060, 3030, 2974, 2922, 2164 (C≡C), 1490, 1452, 1246,
1060 cm–1; MS (CI): m/z (%) = 241 (100) [M + H+], 181 (65),
107 (95), 91 (55); HRMS (CI): m/z calcd for C15H13OS:
241.0687; found: 241.0690; Anal. Calcd for C15H12OS: C,
74.97; H, 5.03; S, 13.34. Found: C, 73.15; H, 4.99; S, 13.25.
1-Ethylsulfinyl-2-phenylacetylene (2b2). Obtained from
thiadiazole 3b (R1 = Ph, 162 mg, 1 mmol) using ethyl iodide
(R2 = Et, 0.4 mL, 5 mmol) as the electrophile gave 2b2 as an
(24) This sulfoxide was successfully prepared by thioether
oxidation: Villar, J. M.; Delgado, A.; Llebaria, A.; Moretó,
J. M.; Molins, E.; Miravitlles, C. Tetrahedron 1996, 52,
10525.
(25) General Procedure for the Synthesis of 1-Alkynyl
Sulfoxides 2: A solution of thiadiazole 3 (1.00 mmol) in
anhyd THF (5 mL) was cooled to –78 °C and MeLi (0.69 mL
of a 1.6 M solution in Et2O, 1.1 mmol) was added dropwise.
After stirring at –78 °C for 1 h, a solution of oxaziridine 1
(267 mg, 1.05 mmol) in anhyd THF (2 mL) was slowly
added dropwise (exothermic reaction). The reaction mixture
was stirred at this temperature for 30 min and treated with
the alkyl halide (1–5 equiv). The reaction mixture was then
warmed to –20 °C over 1.5 h and then the cold bath was
removed. After stirring for a further 1.5 h at r.t., the reaction
mixture was treated with sat. aq NaCl solution and the
product was extracted with Et2O (3 × 20 mL). The combined
organic extracts were washed with sat. aq NaCl solution
(3 × 10 mL) and dried over MgSO4. After filtration and
Synlett 2006, No. 19, 3289–3293 © Thieme Stuttgart · New York

LETTER
orange oil. The product is highly unstable as previously
reported in the literature (31 mg, 0.17 mmol, 17%); Rf = 0.10
(PE–EtOAc, 4:1); 1H NMR (250 MHz, CDCl3): d = 1.51 (t,
J = 7.4 Hz, 3 H), 3.07–3.25 (m, 2 H), 7.34–7.92 (m, 5 H).
(26) (a) Sklute, G.; Marek, I. J. Am. Chem. Soc. 2006, 128, 4642.
(b) Zhao, S. H.; Samuel, O.; Kagan, H. B. Tetrahedron 1987,
43, 5135.
Synthesis of Lithium 1-Alkynesulfenates
3293
(27) (a) Seybold, G.; Heibl, C. Chem. Ber. 1977, 110–1225.
(b) Butler, R. N.; O’Donoghue, D. A. J. Chem. Soc., Perkin
Trans 1 1982, 1223. (c) Rämsby, S. I.; Ögren, S. O.; Ross, S.
B.; Stjernström, N. E. Acta Pharm. Suecica 1973, 10, 285.
Synlett 2006, No. 19, 3289–3293 © Thieme Stuttgart · New York