Phase transfer catalysis (PTC) sulfanylation of some 2-methylsulfinyl- cyclanones

Article abstract of DOI:10.1021/jo048751x

The sulfanylation reactions of 2-methylsulfinylated cyclopentanone, 1-indanone, and cyclohexanone by a PTC procedure are reported and the yields and diastereoselectivity compared to those obtained by the homogeneous-phase method. The stability of the sulf

Full text of DOI:10.1021/jo048751x

SCHEME 1. Sulfanylation Reaction of
2-Methylsulfinylcyclopentanone (1)
Phase Transfer Catalysis (PTC)
Sulfanylation of Some
2-Methylsulfinyl-Cyclanones
Blanka Wladislaw,* Mauro Alves Bueno,
Liliana Marzorati, Claudio Di Vitta, and
Ju´lio Zukerman-Schpector†
Instituto de Quı´mica, Universidade de Sa˜o Paulo,
CEP 05599-970, Sa˜o Paulo, S.P., Brazil, and Centro de
Cieˆncias Exatas e de Tecnologia, Universidade Federal de
Sa˜o Carlos, Sa˜o Carlos, S.P., Brazil
This indicates that only the Re face of the (S)S* enolate
and the Si face of the (S)R* enolate is attacked by the
sulfanylating agent, most probably due to the steric
hindrance. This can be rationalized by assuming that,
in the enolate, the C-O and S-O bonds are in a syn
periplanar orientation, due to interaction of the oxygen
atoms with the ammoniun cation.4 Thus, the CH3 group
would prevent attack at the face on which it is located
(Figure 2). It should be mentioned that this is the first
time that the facial diastereoselectivity of the sul-
fanylation reaction of such sulfinyl cyclanones enolates
could be determined.5
bwlad@iq.usp.br
Received July 21, 2004
Abstract: The sulfanylation reactions of 2-methylsul-
finylated cyclopentanone, 1-indanone, and cyclohexanone by
a PTC procedure are reported and the yields and diastereo-
selectivity compared to those obtained by the homogeneous-
phase method. The stability of the sulfanylated methylsul-
finyl derivatives at room temperature versus the instability
of the p-tolylsulfinyl derivatives is also reported.
These results led us to investigate the sulfanylation
reaction of the 2-p-tolylsulfinylcyclopentanone (3). It has
been reported that 2-p-tolylsulfinylcyclohexanone under-
goes sulfanylation by the homogeneous-phase method, at
low temperature, but that the corresponding sul-
fanylated product is unstable at room temperature and,
therefore, could not be isolated and characterized.5 In
fact, when 3 was submitted to sulfanylation under PTC
conditions, instead of the sulfanylated derivative 4, the
elimination product, 2-methylsulfanylcyclopenten-2-one
(5), was obtained (Scheme 2).
Previous reports from this laboratory1-3 showed that
a solid-liquid PTC procedure is a convenient method for
sulfanylation of some sulfinyl acetophenones, esters, and
thiolesters, as well as R-sulfonyl esters and thiolesters.
This communication reports the sulfanylation of some
racemic 2-sulfinyl cyclanones by the same procedure.
Thus, when 2-methylsulfinylcyclopentanone (1) was sub-
mitted to sulfanylation using K2CO3 as the base, S-
methylmethanethiolsulfonate as the sulfanylating agent,
and benzyltriethylammonium chloride (TEBA) as the
catalyst in CH2Cl2/benzene at room temperature, the
sulfanylated product 2 was obtained in 80% yield (Scheme
1, method A). However, the sulfanylated derivative 2 was
obtained in low yield (39%) employing K2CO3 as the base
and the same sulfanylating agent, but in the absence of
TEBA (Scheme 1, method B). It should be mentioned that
the sulfanylation of 1 by a homogeneous-phase method
also proved to be successful, giving the sulfanylated
product 2 in 84% yield (Scheme 1, method C).
The difference in behavior between cyclic methylsul-
finyl and p-tolylsulfinyl ketones may be attributed to the
difference in leaving group character between p-tolyl and
methylsulfinyl groups.
We then investigated the sulfanylation of 2-methyl-
sulfinyl-1-indanone (6), in which the condensed benzene
ring should increase the planarity of the intermediate
enolate. When 6 was submitted to sulfanylation in the
absence of TEBA, no sulfanylated product was obtained.
However, under PTC conditions, the sulfanylated deriva-
tive 7 was obtained in 85% yield (Scheme 3, method A).
In addition, the sulfanylated derivative 7 was obtained
in only a 70% diastereomeric excess (de) as compared to
the cyclopentanone derivative 2, which was formed as a
single diastereoisomer.
The sulfanylation of 2-methylsulfinylcyclohexanone (8)
by the PTC procedure was successful and gave the
amorphous solid sulfanylated derivative 9 in 75% yield
(Scheme 4, method A). It should be mentioned that the
homogeneous-phase method afforded only a 47% yield
Although the sulfanylation of 1 could give rise to two
diastereoisomers, only one was obtained, independent of
the method employed. This high diastereoselectivity
(100%) is undoubtedly due to the fact that the attack of
the sulfur electrophile occurs only at the unhindered face
of the enolate, which is formed when the R-hydrogen
atom of 1 is removed by base.
The solid 2 was shown to have the 2S*SS* relative
configuration by X-ray analysis (Figure 1).
† Universidade Federal de Sa˜o Carlos.
(1) Wladislaw, B.; Marzorati, L.; Biaggio, F. C. J. Org. Chem. 1993,
58, 6132-6134.
(4) Alvarez-Ibarra, C.; Csa´ky¨, A. G.; Maroto, M.; Quiroga, M. L. J.
Org. Chem. 1995, 60, 6700-6705.
(5) In a study of the sulfanylation of 2-p-tolylsulfinylcyclohexanone,
the sulfanylated derivatives proved to be unstable, precluding assign-
ment of their relative configurations. See: Ruano, J. L. G.; Barros,
D.; Maestro, M. C.; Alcudia, A.; Fernandes, D. Tetrahedron: Asymmetry
1998, 9, 3445-3453.
(2) Wladislaw, B.; Marzorati, L.; Donnici, C. L.; Biaggio, F. C.; Neves,
R. M. A.; Claro Jr., N. F. Phosphorus, Sulfur Silicon 1997, 123, 197-
208.
(3) Wladislaw, B.; Bjo¨rklund, M. B.; Marzorati, L.; Zukerman-
Schpector, J. Phosphorus, Sulfur Silicon 2000, 157, 139-144.
10.1021/jo048751x CCC: $27.50 © 2004 American Chemical Society
Published on Web 11/17/2004
9296
J. Org. Chem. 2004, 69, 9296-9298

FIGURE 1. ZORTEP drawing of 2 in stereoview.
TABLE 1. Yields and de Values for the PTC
Sulfanylationa Reactions of Some Sulfinyl Ketones
yield de
compound
product
(%)
(%)
1
6
8
8
2
80
85
75
93
57
38
73
100
70
20
40
0
15
100
7
9
10b
c
PhCOCH2SOCH3
PhCOCH(SCH3)SOCH3
c
PhCOCH2SOCH(CH3)2 PhCOCH(SCH3)SOCH(CH3)2
PhCOCH2SOC(CH3)3
c
PhCOCH(SCH3)SOC(CH3)3
a Using CH3SSO2CH3; b Using p-TolSSO2CH3; c See ref 3.
FIGURE 2. Preferred conformation for the chelated enolate
of 1.
(Scheme 4, method C) of the sulfanylated product 9. It
is noteworthy that, while the sulfanylated product 9
obtained by the PTC procedure (Scheme 4, method A)
exhibited a de of only 20%, the de of the product from
the homogeneous method (Scheme 4, method C) was 50%.
The higher diastereoselectivity in the latter case is
presumably due to the lower temperature employed (-70
°C). However, the determination of the stereochemical
course of this sulfanylation reaction was only possible by
preparing the crystalline sulfanylated derivative 10
(Scheme 4), whose major diastereoisomer was submitted
to X-ray analysis.
The major diastereoisomer of 10 was shown to have
the 2S*SS* configuration (Figure 3) and, therefore, the
same as that of the sulfanylated cyclopentanone deriva-
tive 2.
Table 1 shows the yields and de values for the sul-
fanylation of some 2-sulfinyl cyclanones, in compari-
son to some open-chain ketosulfoxides, previously sul-
fanylated in our laboratory by the PTC method.3
FIGURE 3. ORTEP drawing of the major diastereoisomer of
10 in stereoview.
The 100% de value for 2 is the same as that for the
open-chain tert-butyl derivative, being, in both cases, of
steric origin. Further studies on the sulfanylation of
enantiomerically pure 2-methylsulfinyl cyclanones will
be reported in due course.
In summary, it has been shown that the PTC procedure
is a convenient method for obtaining sulfanylated 2-
SCHEME 2. Sulfanylation Reaction of 2-p-Tolylsulfinylcyclopentanone (3)
J. Org. Chem, Vol. 69, No. 26, 2004 9297

TolSSO2CH3 (0.50 mmol), solid K2CO3 (1.0 mmol), and TEBA
(0.10 mmol) in 5 mL of benzene/dichloromethane (1:1, v/v) was
vigorously stirred at room-temperature. The reaction progress
was monitored by TLC, and after reaching equilibrium, the
mixture was diluted with dichloromethane and the solid removed
by vacuum filtration. After concentration of the filtrate, the crude
product was purified by chromatography (TLC; n-hexane/ethyl
acetate, 3:2, v/v).
SCHEME 3. Sulfanylation Reaction of
2-Methylsulfinyl-1-indanone (6)
Method C (Homogeneous-Phase). n-Butyllithium (0.58 mL
of a 2 M solution in hexanes, 1.2 mmol) was added dropwise to
a cooled solution (0 °C) of diisopropylamine (0.16 mL, 1.2 mmol)
in 10 mL of THF. After 10 min of stirring, the solution was cooled
to -78 °C, and the 2-methylsulfinyl cyclanone (1.1 mmol)
dissolved in 3 mL of THF was added via syringe. Stirring was
maintained for 30 min at the same temperature, and CH3SSO2-
CH3 (1.1 mmol) in THF (5 mL) was added. After 5 h, the reaction
was quenched with a saturated aqueous solution of NH4Cl (10
mL) and extracted with chloroform (3 × 15 mL). The organic
extract was dried (MgSO4), the solvent removed under vacuum,
and the crude product purified by TLC (n-hexane/ethyl acetate,
3:2, v/v).
SCHEME 4. Sulfanylation of
2-Methylsulfinylcyclohexanone (8)
Acknowledgment. We acknowledge FAPESP for
financial support and CNPq for grants. We also thank
Professor F. H. Quina for revising the manuscript.
methylsulfinyl cyclanones in good yields and, in some
cases, in high de. A rationalization for the observed facial
diastereoselectivity of the performed sulfanylation reac-
tion is proposed.
Supporting Information Available: Characterization
data for compounds 1-3 and 5-10 and 1H and 13C NMR
spectra of compounds 2, 6, 7, 9, and 10 (CIF, PDF). This
material is available free of charge via the Internet at
http://pubs.acs.org.
Experimental Section
General Procedures for the Sulfanylation of 2-Methyl-
sulfinyl Cyclanones: Method A (PTC). A mixture of the
2-methylsulfinyl cyclanone (0.50 mmol), CH3SSO2CH3 or p-
JO048751X
9298 J. Org. Chem., Vol. 69, No. 26, 2004