Mild preparation of alkenes from phenyl sulfides: One-pot elimination of phenylthio group via sulfilimine at ambient temperature

Article abstract of DOI:10.1021/ol062620w

(Chemical Equation Presented) Various alkenes were prepared from phenyl sulfides in a one-pot manner at room temperature by converting them to the corresponding S-aminosulfonium salts with O-mesitylenesulfonylhydroxylamine, followed by treatment with pota

Full text of DOI:10.1021/ol062620w

ORGANIC
LETTERS
2006
Vol. 8, No. 26
6095-6098
Mild Preparation of Alkenes from Phenyl
Sulfides: One-Pot Elimination of
Phenylthio Group via Sulfilimine at
Ambient Temperature
Jun-ichi Matsuo,* Takaaki Kozai, and Hiroyuki Ishibashi*
DiVision of Pharmaceutical Sciences, Graduate School of Natural Science and
Technology, Kanazawa UniVersity, Kakuma-machi, Kanazawa 920-1192, Japan
jimatsuo@p.kanazawa-u.ac.jp
Received October 25, 2006
ABSTRACT
Various alkenes were prepared from phenyl sulfides in a one-pot manner at room temperature by converting them to the corresponding
S-aminosulfonium salts with O-mesitylenesulfonylhydroxylamine, followed by treatment with potassium carbonate. Alkenes were formed by
cis-elimination of in situ generated phenyl sulfilimines.
Pyrolysis reactions of esters,1 xanthates,2 amine oxides,3
sulfoxides,4 and selenoxides5 are important for the synthesis
of alkenes.6 Phenyl sulfides are useful precursors of alkenes
since they are relatively tolerant of basic and acidic condi-
tions, and cis-elimination of their sulfoxides proceeds at
temperatures ranging from 100 to 150 °C.4 It could be
expected that the synthetic utility of the elimination would
be enhanced if the elimination could be induced under milder
conditions such as at room temperature.
compounds to the corresponding R,â-unsaturated carbonyl
compounds via sulfilimine 2 even at -78 °C in a few minutes
(Scheme 1).8 Compared to the elimination of the R-phenyl-
Scheme 1. Milder Elimination of 2 than 3
We have been studying the unique reactivity of N-tert-
butylbenzenesulfinimidoyl chloride (1)7 as an oxidizing
agent, and we found that 1 dehydrogenated carbonyl
(1) (a) Hurd, C. D.; Blunck, F. H. J. Am. Chem. Soc. 1938, 60, 2419-
2425. (b) Barton, D. H. R. J. Chem. Soc. 1949, 2174-2178. (c) Curtin, D.
Y.; Keiiom, D. B. J. Am. Chem. Soc. 1953, 75, 6011-6018.
(2) (a) Nace, H. R. Org. React. 1962, 12, 57-100. (b) Cram, D. J. J.
Am. Chem. Soc. 1949, 71, 3883-3889. (c) Cram, D. J.; Abd Elhafez, F. A.
J. Am. Chem. Soc. 1952, 74, 5828-5835. (d) Alexander, E. R.; Mudrak,
H. J. Am. Chem. Soc. 1950, 72, 1810-1813.
(3) Cope, A. C.; Trumbull, E. R. Org. React. 1960, 11, 317-493.
(4) (a) Field, L. Synthesis 1972, 101-133. (b) Field, L. Synthesis 1978,
713-740. (c) Trost, B. M.; Salzman, T. N.; Hiroi, K. J. Am. Chem. Soc.
1976, 98, 4887-4902. (d) Trost, B. M. Acc. Chem. Res. 1978, 11, 453-
461. (e) Trost, B. M. Chem. ReV. 1978, 78, 363-382.
sulfinyl group from 3, which required reaction temperatures
ranging from 100 to 150 °C for several hours,4 the 1-medi-
ated dehydrogenation proceeded under surprisingly mild
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conditions. It was thought that the differences in reactivity
between sulfilimine 2 and sulfoxide 3 arose from the en-
hanced basicity of the nitrogen in 2 compared to the oxygen
in 3. Along the same lines, we speculated that elimination
of sulfilimines 4 would proceed under milder conditions than
those for elimination of sulfoxides 5 (Scheme 2). Several
4a from phenyl sulfides failed in spite of many trials, and
so we then planned to prepare N-H sulfilimines from phenyl
sulfides. Among some methods known for the preparation
of N-H sulfilimines from phenyl sulfides,16,17 the use of
O-mesitylenesulfonylhydroxylamine (MSH)18 was chosen as
this reagent seemed to allow N-H sulfilimines to be prepared
under mild conditions.17
Phenyl sulfide 6 was treated with MSH at 0 °C in
dichloromethane to generate S-aminosulfonium salt 7 (Scheme
3). Quantitative formation of 7 was confirmed by H NMR
Scheme 2. Comparison between Elimination of 4 and That of
1
5
Scheme 3. One-Pot Elimination of 6 to 9 Using MSH
examples of elimination of N-substituted sulfilimines,9
including N-ethoxycarbonyl-,10 N-tosyl-,11 N-carbamoyl-,12
N-acyl-,13 N-phenyl-,14 and N-H sulfilimines,15 have been
reported. However, sulfilimines that have an electron-
withdrawing group on the nitrogen atom (R3 of 4 ) electron-
withdrawing group) required elevated temperatures for
elimination. We therefore planned to establish a new method
for the efficient and mild elimination of sulfilimines that do
not have an electron-withdrawing group (R3 of 4 * electron-
withdrawing group). We describe here a one-pot elimination
of phenyl sulfides to alkenes via N-H sulfilimines that
proceeds at ambient temperature which is also applicable to
the synthesis of R,â-unsaturated carbonyl compounds.
First, we investigated elimination of sulfilimines bearing a
tert-butyl group on the nitrogen atom (R3 of 4 ) tert-butyl)
expecting mild elimination as observed in the intermediate
2. However, preparation of N-tert-butyl phenyl sulfilimines
analysis of a mixture of 6 and MSH in CDCl3.19 Then suitable
bases needed for the in situ generation of sulfilimine 8 from
7 were screened (Table 1). The use of DBU directly gave
Table 1. Effect of Bases on One-Pot Elimination of Phenyl
Sulfide 6 to Alkene 9a
entry
base (equiv)
yield (%)b
recovered 6 (%)b
1
2
3
4
5
6
i-Pr2NEt (2)
DBU (2)
t-BuOK (1.5)
K2CO3 (10)
K2CO3 (10) + MS4A
CsF (5)
0
0
16
8
6
10
6
42
78
80
80
83
a For reaction conditions, see Scheme 3. b Determined by 1H NMR
analysis.
(5) (a) Clive, D. L. J. Tetrahedron 1978, 34, 1049-1132. (b) Reich, H.
J. Acc. Chem. Res. 1979, 12, 22-30. (c) Paulmier, C. In Selenium Reagents
and Intermediates in Organic Synthesis; Pergamon Press: Oxford, 1986.
(6) Review: (a) Depuy, C. H.; King, R. W. Chem. ReV. 1960, 60, 431-
457. (b) Astles, P. C.; Mortlock, S. V.; Thomas, E. J. In ComprehensiVe
Organic Synthesis; Trost, B. M., Fleming, I., Heathcock, C. H., Eds.;
Pergamon Press: New York, 1991; Vol. 6, pp 1011-1039.
(7) Matsuo, J. J. Synth. Org. Chem. Jpn. 2004, 62, 574-583.
(8) (a) Mukaiyama, T.; Matsuo, J.; Kitagawa, H. Chem. Lett. 2000,
1250-1251. (b) Matsuo, J.; Aizawa, Y. Tetrahedron Lett. 2005, 46, 407-410.
(9) Gilchrist, T. L.; Moody, C. J. Chem. ReV. 1977, 77, 409-435.
(10) Whitfield, G. F.; Beilan, H. S.; Saika, D.; Swern, D. J. Org. Chem.
1974, 39, 2148-2152.
alkene 9 in 42% yield even at room temperature, while
diisopropylethylamine did not give 9 (entries 1 and 2). The
use of potassium tert-butoxide improved the yield of alkene
9 to 78% yield (entry 3). Inorganic bases such as potassium
carbonate and cesium fluoride were found to be effective,
and the presence of molecular sieves 4A did not affect the
efficiency of the elimination (entries 4-6). As described
(11) (a) Oae, S.; Tsujihara, K.; Furukawa, N. Tetrahedron Lett. 1970,
2663-2666. (b) Tsujihara, K.; Furukawa, N.; Oae, S. Tetrahedron 1971, 27,
4921-4930. (c) Tsujihara, K.; Harada, K.; Furukawa, N.; Oae, S. Tetrahed-
ron 1971, 27, 6101-6108. (d) Oae, S.; Harada, K.; Tsujihara, K.; Furukawa,
N. Bull. Chem. Soc. Jpn. 1973, 46, 3482-3486. (e) Furukawa, N.; Hatanaka,
T.; Harada, K.; Oae, S. Bull. Chem. Soc. Jpn. 1976, 49, 2337-2338.
(12) Oae, S.; Masuda, T.; Tsujihara, K.; Furukawa, N. Bull. Chem. Soc.
Jpn. 1972, 45, 3586-3590.
(16) Furukawa, N.; Omata, T.; Yoshimura, T.; Aida, T.; Oae, S.
Tetrahedron Lett. 1972, 1619-1622.
(17) Tamura, Y.; Sumoto, K.; Minamikawa, J.; Ikeda, M. Tetrahedron
Lett. 1972, 4137-4140.
(18) (a) Tamura, Y.; Minamikawa, J.; Sumoto, K.; Fujii, S.; Ikeda, M.
J. Org. Chem. 1973, 38, 1239-1241. (b) Johnson, C. R.; Kirchhoff, R. A.;
Corkins, H. G. J. Org. Chem. 1974, 39, 2458-2459.
(19) We observed that phenyl sulfide 6 hardly reacted with hydroxy-
lamine-O-sulfonic acid (HAS) even at room temperature, while Appel
reported that dimethylsulfide and diethylsulfide reacted with HAS to give
the corresponding S-aminosulfonium salts. See: Appel, R.; Buchiner, W.
Chem. Ber. 1962, 95, 849-854.
(13) (a) Papa, A. J. J. Org. Chem. 1970, 35, 2837-2840. (b) Kise, H.;
Whitfield, G. F.; Swern, D. J. Org. Chem. 1972, 37, 1125-1128.
(14) Gassman, P. G.; Gruetzmacher, G. D. J. Am. Chem. Soc. 1974, 96,
5487-5495.
(15) Appel, R.; Bu¨chner, W. Chem. Ber. 1962, 95, 855-866.
6096
Org. Lett., Vol. 8, No. 26, 2006

above, phenyl sulfide 6 was completely converted to 7 by
the reaction of MSH, but phenyl sulfide 6 was regenerated
in 6-16% yield after treating 7 with bases (entries 2-6).
These results are in accordance with results of a previous
report mentioning that N-H sulfilimines decompose readily
to sulfide, NH3, and N2 at room temperature.16 Our results
suggest that the regeneration of 6 was influenced by the bases
employed and that bases such as potassium carbonate and
cesium fluoride minimize the decomposition of 8 to 6.
The effects of solvents were next examined using potas-
sium carbonate as a base (Table 2). It was found that the
Scheme 4. Stereochemistry
Table 2. Effect of Solvents on One-Pot Elimination of Phenyl
Sulfide 6 to Alkene 9a
carbonate, and dichloromethane (Table 3). Longer reaction
times were sometimes needed for converting S-aminosulfo-
nium salts to alkenes. Protecting groups such as PMB, BOM,
and TBDPS groups were tolerant of the MSH-mediated
elimination of phenyl sulfides (entries 1-3). It should be
noted that enamide 12e was obtained in good yield as in the
case of generating N-allyl amide 12d (entries 3-4). Thus,
the present method would be applicable to the preparation
of labile olefinic compounds.
entry
solvent
yield (%)b
1
2
3
4
5
6
7
toluene
CH2Cl2
Et2O
82
80 (77)
18
75
79
THF
CH3CN
MeNO2
DMF
77
80 (76)
a For reaction conditions, see Scheme 3. b Determined by 1H NMR
analysis. Numbers in parentheses are isolated yields.
In order to investigate the stereochemistry of the present
elimination reaction, diastereoisomeric phenyl sulfides 13 and
16 were subjected to the present elimination reaction
(Scheme 4). Phenyl sulfide 13 gave 14 in 85% yield, and
present elimination proceeded smoothly in both polar and
nonpolar solvents except diethyl ether. In the case of diethyl
ether, 9 was formed in only 18% yield, probably due to the
low solubility of S-aminosulfonium salt 7 in diethyl ether
(entry 3). Dichloromethane was generally employed as a
solvent in this elimination since it was observed that
S-aminosulfonium salts were sometimes insoluble in toluene
when another phenyl sulfide was employed. Alkene 9 was
isolated by thin-layer column chromatography on silica gel
after organic extracts were washed with diluted NaOCl
solution in order to oxidize benzenesulfenamide 10 and
regenerated phenyl sulfide 6 (entries 2 and 7).
1
isomer 15 was not detected by H NMR analysis. On the
other hand, phenyl sulfide 16 afforded 14 and 15 in a ratio
of 1:40 after 3 h. It was found that 15 isomerized to 14 since
Table 4. Elimination of the R-Phenylthio Group of 17a-c to
R,â-Unsaturated Carbonyl Compounds 18a-c Using MSH and
K2CO3
Next, the scope and limitations of the present elimination
via sulfilimines were examined using MSH, potassium
Table 3. Mild One-Pot Elimination of Phenyl Sulfides 11a-e
to Alkenes 12a-e
entry
R
reaction time (h) product yield (%)a
1
2
3
4
5
PMBO(CH2)3 11a
BOMO(CH2)3 11b
TBDPS(CH2)3 11c
6
6
24
12
12
12a
12b
12c
12d
12e
83
76
77
78
65
BzNHCH2
BzNH
11d
11e
a Isolated yield.
a Isolated yield.
Org. Lett., Vol. 8, No. 26, 2006
6097

a longer reaction time (6 h) changed the ratio of 14/15 )
1:40 to 14/15 ) 1:3.6. Therefore, it was confirmed that the
present elimination of sulfilimine proceeded by cis-elimina-
tion. Moreover, the present elimination gave 15 more
stereoselectively than elimination of N-Ts sulfilimine of 16
(80 °C, 5 h, 14/15 ) 1:17).11c
intermediates, N-H sulfilimines, were unstable and decom-
posed to sulfides;16 however, we found that cis-elimination
took place as the major reaction pathway by the present
procedure. The mildness and efficiency of the present
elimination reaction would be useful for introduction of
carbon-carbon double bonds in various kinds of molecules.
Finally, the present method was applied to conversion of
R-phenylthio carbonyl compounds to obtain R,â-unsaturated
carbonyl compounds (Table 4). The elimination proceeded
in a one-pot manner at ambient temperature to afford R,â-
unsaturated esters (18a, b) and amide (18c) in high yields.
It should be noted that only (E)-isomers were obtained in
the case of acyclic substrates and that MSH-mediated
elimination of R-phenylthio carbonyl compounds gave the
corresponding R,â-unsaturated carbonyl compounds more
efficiently than that of phenyl sulfides to alkenes (Tables 3
and 4).
Acknowledgment. We are grateful for the financial
support from Takeda Science Foundation, and this work was
partially supported by a Grant-in-Aid for Scientific Research
from the Ministry of Education, Culture, Sports, Science,
and Technology of Japan.
Supporting Information Available: Experimental pro-
cedures for elimination and spectral data for phenyl sulfides
(6, 11a-e, 13, 16, and 17a-c) and elimination products (9,
12a-e, and 18a-c). This material is available free of charge
via the Internet at http://pubs.acs.org.
In summary, various alkenes were prepared from phenyl
sulfides in a one-pot manner at room temperature using MSH
and potassium carbonate. It was previously thought that the
OL062620W
6098
Org. Lett., Vol. 8, No. 26, 2006