m-CPBA/KOH as a Nucleophilic Epoxidation of gem-Deactivated Olefins
sulfoxide 2425,26 (43 mg, 0.18 mmol) and m-CPBA (57 mg, 0.28
mmol) after 1 h of reaction. Purification by flash column
chromatography (ethyl acetate-hexane, 1:2) gave pure sulfone
25 (44 mg, yield 96%) as a white solid (ethyl ether), which
decomposed at temperatures higher than 175 °C: IR (film)
1702; 1H NMR δ 7.92 and 7.31 (AA′BB′ system, 4H), 2.71 (m,
2H), 2.62 (s, 3H), 2.41 (s, 3H), 2.39 (m, 2H); 13C NMR δ 199.9,
184.8, 144.8, 139.5 and 137.5 (C), 129.5 and 128.3 (CH), 34.3
and 33.6 (CH2), 21.6 and 18.9 (CH3).
General Procedure for Oxidation with m-CPBA/K2CO3
(GP2). To a mixture of m-CPBA (0.50 mmol) and K2CO3 (0.24
mmol) in dry CH2Cl2 (6.5 mL), under argon at room temper-
ature, was added a solution of the corresponding substrate (0.2
mmol) in dry CH2Cl2 (2.6 mL). After 3 h, the reaction mixture
was washed with a NaHSO3 solution (40%) and then with
saturated aqueous NaHCO3. The organic layer was dried (Na2-
SO4), filtered, and concentrated in vacuo. It was purified by
flash column chromatography (ethyl acetate-hexane, 1:4).
1-[(4-Methylphenyl)sulfonyl]-6-oxabicyclo[3.1.0]hexan-
2-one (7). Compound 7 was obtained from sulfinylcyclopen-
tenone 2225 following GP2: yield 99%; white solid (hexane);
mp 138-139 °C; IR (KBr) 1743; 1H NMR δ 7.96 and 7.38
(AA′BB′ system, 4H), 4.58 (d, J ) 1.8 Hz, 1H), 2.45 (s, 3H),
2.42-2.29 (m, 3H), 2.28-2.14 (m, 1H); 13C NMR δ 200.1, 146.0,
and 133.9 (C), 129.8 and 129.6 (CH), 70.8 (C), 65.2 (CH), 33.3
(CH2), 21.8 (CH3), 21.3 (CH2).
(1SR,4SR,5RS)-4-Ethoxy-1-[(4-methylphenyl)sulfonyl]-
3,6-dioxabicyclo[3.1.0]hexan-2-one (9). Compound 9 was
synthesized by GP2 modified as follows: sulfone 8 (37 mg, 0.13
mmol) was oxidized using m-CPBA (30 mg, 0.15 mmol) and
K2CO3 (9 mg, 0.06 mmol). The reaction time was 30 min. Flash
column chromatography (ethyl acetate-hexane, 1:6) gave pure
epoxide 9 (29 mg, 75%). Compound 9 was also obtained
following GP1 from sulfone 8 (38 mg, 0.13 mmol) and m-CPBA
(31 mg, 0.15 mmol) after 24 h of reaction. The same purifica-
tion as described above gave pure epoxide 9 (30 mg, yield 77%)
as a white solid: mp 152-153 °C; IR (KBr) 1796, 1596, 1158;
1H NMR δ 7.99 and 7.43 (AA′BB′ system, 4H), 5.42 (s, 1H),
4.67 (s, 1H), 3.96 (m, 1H), 3.72 (m, 1H), 2.48 (s, 3H), 1.29 (t, J
) 7.1 Hz, 3H); 13C NMR δ 163.1, 146.8 and 132.6 (C), 130.0
and 129.8 (CH), 99.0 (CH), 66.7 (CH2), 65.8 (C), 62.6 (CH), 21.8
and 14.7 (CH3). Anal. Calcd for C13H14O6S: C, 52.34; H, 4.73;
S, 10.75. Found: C, 52.38; H, 4.66; S, 10.99.
5-Methyl-1-[(4-methylphenyl)sulfonyl]-6-oxabicyclo-
[3.1.0]hexan-2-one (27). Compound 27 was obtained from
sulfinylcyclopentenone 2425,26 following GP2: yield 88%; white
solid (hexane); mp 115-116 °C; IR (KBr) 1748; 1H NMR δ 7.97
and 7.37 (AA′BB′ system, 4H), 2.45 (s, 3H), 2.35-2.06 (m, 4H),
2.04 (s, 3H); 13C NMR δ 202.0, 145.7 and 135.2 (C), 129.6 and
129.5 (CH), 76.1 and 73.8 (C), 32.4 and 27.9 (CH2), 21.7 and
16.3 (CH3). Anal. Calcd for C13H14O4S: C, 58.63; H, 5.30; S,
12.04. Found: C, 58.67; H, 5.34; S, 12.00.
same as described for GP1. Flash column chromatography
(ethyl acetate-hexane, 1:4) gave pure epoxide 15 (21 mg, yield
84%) as a colorless oil: IR (film) 1751; 1H NMR δ 7.78 and
7.36 (AA′BB′ system, 4H), 4.72 (d, J ) 2.8 Hz, 1H), 3.92 (d, J
) 2.8 Hz, 1H), 3.75 (s, 3H), 3.64 (m, 2H), 3.51 (m, 2H), 2.46 (s,
3H), 1.15 (2t, J ) 6.9 Hz, 6H); 13C NMR δ 162.0, 146.2 and
132.6 (C), 129.8, 129.4 and 96.8 (CH), 72.1 (C), 62.4 and 62.0
(CH2), 61.2 (CH), 53.1, 21.7, and 14.9 (CH3). Anal. Calcd for
C16H22O7S: C, 53.62; H, 6.19; S, 8.95. Found: C, 53.43; H, 6.26;
S, 8.76.
Methyl 2-[(4-Methylphenyl)sulfonyl]-3-phenyloxirane-
2-carboxylate (16). Compound 16 was obtained following
GP3 from alkene 1128 (50 mg, 0.16 mmol), m-CPBA (97 mg,
0.47 mmol), and KOH (52 mg, 0.79 mmol) after 7 h of reaction.
Flash column chromatography (ethyl acetate-hexane, 1:5)
gave a pure epoxide 16 (44 mg, yield 83%) as a white solid
1
(ethyl ether): mp 94-96 °C; IR (film) 1750; H NMR δ 7.83
and 7.40 (AA′BB′ system, 4H), 7.29 (m, 5H), 4.86 (s, 1H), 3.52
(s, 3H), 2.47 (s, 3H); 13C NMR δ 161.7, 146.3, 132.9 and 130.4
(C), 130.0, 129.6, 129.4, 128.6 and 126.1 (CH), 65.8 (C), 62.1
(CH), 53.2 and 21.8 (CH3).
General Procedure A for the Preparation of Sulfinyl
Epoxides (GP4A). A mixture of m-CPBA (0.56 mmol) and
KOH (0.62 mmol) in dry CH2Cl2 (7.3 mL) was stirred under
argon at room temperature for 1 h. It was cooled at -20 °C,
and a solution of the corresponding sulfoxide (0.28 mmol) in
dry CH2Cl2 (3.6 mL) was added. After the time indicated in
each case, the reaction mixture was washed with NaHSO3
solution (40%) and then with saturated aqueous NaHCO3. The
organic layer was dried (Na2SO4), filtered, and concentrated
in vacuo. It was purified by flash column chromatography
(ethyl acetate-hexane, 1:2).
General Procedure B for the Preparation of Sulfinyl
Epoxides (GP4B). A solution of the corresponding sulfoxide
(0.30 mmol) and Yb(OTf)3 (0.30 mmol) in dry CH2Cl2 (3.9 mL)
was stirred under argon at room temperature during 1 h.
Then, it was added to a mixture of m-CPBA (0.6 mmol) and
KOH (0.66 mmol) in dry CH2Cl2 (7.8 mL), previously stirred
at room temperature for 1 h and then cooled at the tempera-
ture indicated in each case. After the time indicated in each
case, the reaction mixture was washed with a NaHSO3 solution
(40%), saturated aqueous NaHCO3, and a saturated solution
of NH4Cl. The organic layer was dried (Na2SO4), filtered off,
and concentrated under vacuum. It was purified by flash
column chromatography (ethyl acetate-hexane, 1:2).
[1SR,5RS,(S)RS]-1-[(4-Methylphenyl)sulfinyl]-6-oxa-
bicyclo[3.1.0]hexan-2-one (23a). This compound was ob-
tained from sulfinylcyclopentenone 2225 as a mixture of
diastereoisomers (23a/23b 70:30) following GP4A after 15 min
of reaction (combined yield 84%). Sulfinyl epoxide 23a was
obtained as the sole compound following GP4B from sulfinyl-
cyclopentenone 22 after 1 h of reaction at 0 °C: yield 80%;
white solid (ethyl ether/hexane); mp 85-86 °C; IR (KBr) 1737;
1H NMR δ 7.65 and 7.32 (AA′BB′ system, 4H), 4.33 (m, 1H),
2.41 (s, 3H), 2.49-2.30 (m, 2H), 2.21-2.15 (m, 1H), 2.03-1.92
(m, 1H); 13C NMR δ 203.3, 142.9 and 136.3 (C), 130.0 and 125.7
(CH), 74.0 (C), 61.1 (CH), 33.4 and 21.7 (CH2), 21.5 (CH3). Anal.
Calcd for C12H12O3S: C, 61.00; H, 5.12; S, 13.57. Found: C,
60.94; H, 5.16; S, 13.37.
General Procedure for the Epoxidation with m-CPBA/
KOH (GP3). A mixture of m-CPBA and KOH (the amounts
of reagents are indicated in each case) in dry CH2Cl2 (13 mL/
mmol) was stirred under argon at room temperature for 1 h.
A solution of alkene (1 equiv) in dry CH2Cl2 (13 mL/mmol) was
added at room temperature. The reaction was monitored by
TLC. The mixture was filtered off, washed with dichlo-
romethane, and concentrated under vacuum. The reaction time
and the purification method are indicated in each case.
Methyl (2SR,3RS)-3-(Diethoxymethyl)-2-[(4-methyl-
phenyl)sulfonyl]oxirane-2-carboxylate (15). Compound 15
was obtained following GP3 from alkene 1027 (24 mg, 0.07
mmol), m-CPBA (18 mg, 0.09 mmol), and KOH (6 mg, 0.09
mmol) after 3 h of reaction. In this case, the workup is the
[1RS,5SR,(S)RS]-1-[(4-Methylphenyl)sulfinyl]-6-oxa-
bicyclo[3.1.0]hexan-2-one (23b). This compound was ob-
tained from sulfinylcyclopentenone 2225 as a mixture of
diastereoisomers (23a/23b 70:30) following GP4A after 15 min
of reaction (combined yield 84%). It could not be isolated as a
pure isomer. The signals were measured from the spectrum
of a mixture of 23a and 23b in a ratio of 70:30: 1H NMR δ
7.67 and 7.32 (AA′BB′ system, 4H), 4.30 (m, 1H), 2.41 (s, 3H),
2.49-2.30 (m, 2H), 2.21-2.15 (m, 1H), 2.03-1.92 (m, 1H); 13C
NMR δ 204.6, 142.6 and 135.3 (C), 129.8 and 125.4 (CH), 75.1
(C), 64.6 (CH), 33.5 and 29.6 (CH2), 22.0 (CH3).
(25) Hulce, M.; Mallazo J. P.; Frye, L. L.; Bogan, T. P.; Posner, G.
H. Org. Synth. 1985, 64, 196-206.
(26) Posner, G. H.; Kogan, T. P.; Hulce, M. Tetrahedron Lett. 1984,
25, 383-386.
(27) Garc´ıa Ruano, J. L.; Fajardo, C.; Mart´ın, M. R. Tetrahedron.
2005, 61, 4363-4371.
(28) Reedy, G. R.; Gupta, S. V. S. A. K.; Reedy, D. B.; Seenaiah, B.
J. Indian Chem. Soc. 1992, 69, 396-397.
J. Org. Chem, Vol. 70, No. 11, 2005 4305