Addition to 2-(Arylsulfinyl)-2-cycloalkenones
J . Org. Chem., Vol. 62, No. 22, 1997 7799
dried at 50 °C under reduced pressure to give the sodium salt
12 (16.6 g, 69%).
readily removed, these reactions provide a preparative
method for chiral 3-alkyl-1-cyclopentanones and -cyclo-
hexanones.
To thionyl chloride (32.5 mL, 445 mmol) was added por-
tionwise the sodium salt 12 (17.2 g, 59.4 mmol) over a period
of 1 h and the mixture was vigorously stirred at room
temperature for 2.5 h. Excess amount of thionyl chloride was
stripped off under reduced pressure. To the residual oil was
added Et2O (50 mL) and then added dropwise a solution of
diacetone D-glucose (14.1 g, 54.0 mmol) and pyridine (6.70 mL,
89.1 mmol) in Et2O (50 mL) at 0 °C over a period of 20 min.
After stirring overnight at room temperature, the mixture was
poured into 1 mol/L HCl (50 mL) and extracted with Et2O.
The combined organic extracts were washed with saturated
NaHCO3 (20 mL), water (20 mL), and brine (20 mL). The
solution was dried over MgSO4 and concentrated to give the
crude sulfinate. It was purified by column chromatography
(silica gel, hexane/ethyl acetate ) 92/8) to give a diastereomeric
Exp er im en ta l Section
P r ep a r a tion of th e Ch ir a l Su lfin a tes. (R)-(+)-Men th yl
3,5-Di-ter t-bu tyl-4-m eth oxyben zen esu lfin a te ((R)-2). To
a solution of 2,6-di-tert-butylanisole (6)12 (31.3 g, 0.142 mol)
in CHCl3 (60 mL) was added dropwise chlorosulfonic acid (18.9
mL, 0.284 mol) over a period of 30 min at -10 °C. After
stirring for 10 min, the mixture was poured onto crushed ice
(200 mL) and extracted with CHCl3. The combined organic
extracts were washed with brine, dried over MgSO4, and
concentrated under reduced pressure to leave a solid, which
was purified by recrystallization from hexane, giving the
sulfonyl chloride 8 (19.9 g, 44%) as a colorless solid: Rf ) 0.58
(hexane/ethyl acetate ) 9/1); mp 90.2-90.7 °C; 1H NMR δ 1.46
(s, 18H), 3.76 (s, 3H), 7.90 (s, 2H); 13C NMR δ 31.6, 36.4, 64.9,
125.7, 138.5, 146.3, 165.6; IR (KBr) 2850, 1440, 1370, 1215,
1165, 1110, 995 cm-1; MS (EI) m/ e 318 (M+, 23), 303 (100).
Anal. Calcd for C15H23ClO3S: C, 56.50; H, 7.27. Found: C,
56.44; H, 7.33.
The aqueous solution obtained in the above experiment was
acidified with concentrated HCl and extracted with CHCl3 and
successively with aqueous NaHCO3, and the resultant solution
was cooled to precipitate the sodium sulfonate, which was also
converted to the sulfonyl chloride 8. To a solution of the
sodium sulfonate (21.3 g, 0.066 mmol) in DMF (100 mL) was
added dropwise thionyl chloride (14.4 mL, 0.198 mol) at 0 °C
over a period of 90 min. Then the mixture was allowed to
warm to room temperature and stirred for 1 h. The mixture
was poured onto crushed ice (200 mL) and extracted with Et2O.
The combined organic extracts were washed with saturated
NaHCO3 (50 mL), water (50 mL), and brine (50 mL). The
organic solution was dried over MgSO4 and concentrated to
leave a solid, which was purified by recrystallization from
hexane to give the sulfonyl chloride 8 (17.7 g, 84%).
mixture of the sulfinate 4 (20.5 g, 73%) in a ratio of SR:SS
)
38:62, which was determined by 1H NMR. Each diastereo-
isomer was isolated by flash column chromatography. Fur-
ther, the (R)-diastereoisomer was purified by recrystallization
from hexane/Et2O.
(R)-(+)-Dia ceton e D-Glu cose 2,4,6-Tr iisop r op ylben ze-
n esu lfin a te Ester ((R)-3): Rf ) 0.64 (hexane/ethyl acetate )
8/2); HPLC tR ) 9.90 min (eluent, hexane/ethyl acetate ) 85/
1
15); mp 142.3-143.0 °C; [R]18 ) +11.0 (c 1.04, acetone); H
D
NMR δ 1.17, 1.34, 1.39, 1.51 (4s, 12H), 1.24, 1.28 (2d, J ) 6.9,
6.9 Hz, 18H), 2.77-3.00 (m, 1H), 3.91-4.07 (m, 5H), 4.19 (dd,
J ) 2.7, 7.9 Hz, 1H), 4.84 (d, J ) 2.7 Hz, 1H), 4.88 (d, J ) 3.6
Hz, 1H), 5.89 (d, J ) 3.6 Hz, 1H), 7.08 (s, 2H); 13C NMR δ
23.7, 24.2, 24.5, 25.1, 26.3, 26.9, 28.2, 34.4, 67.2, 72.0, 80.8,
82.6, 84.0, 105.3, 109.2, 112.5, 122.7, 137.9, 148.7, 153.2; IR
(KBr) 2950, 1595, 1455, 1370, 1250, 1210, 1130, 1070, 1020
cm-1; MS (EI) m/ e 510 (M+, 0.1), 495 (6), 250 (100), 233 (95).
Anal. Calcd for C27H42O7S: C, 63.50; H, 8.29. Found: C,63.40;
H, 8.39.
(S)-(-)-Dia ceton e D-Glu cose 2,4,6-Tr iisop r op ylben ze-
n esu lfin a te Ester ((S)-3): Rf ) 0.59 (hexane/ethyl acetate )
8/2); HPLC tR ) 11.18 min (eluent, hexane/ethyl acetate ) 85/
1
15); [R]18 ) -36.2 (c 0.636, acetone); H NMR δ 1.25, 1.36,
To a solution of the sulfonyl chloride 8 (3.20 g, 10.0 mmol)
and (-)-(l)-menthol (1.05 g, 6.69 mmol) in CH2Cl2 (32 mL) were
added trimethyl phosphite (1.58 mL, 13.4 mmol) and triethyl-
amine (1.40 mL, 10.0 mmol) at room temperature. After
heating under reflux for 8 h, the mixture was cooled to room
temperature. The mixture was poured into 1 mol/L HCl (30
mL) and extracted with Et2O. The combined organic extracts
were washed with saturated NaHCO3 (10 mL), water (2 × 10
mL), and brine (10 mL). The solution was dried over MgSO4
and concentrated to give the crude sulfinate, which was
purified by column chromatography (silica gel, hexane/ethyl
acetate ) 98/2) to give the sulfinate 2 (1.95 g, 70%) as a
mixture of diastereoisomers. Optically pure the sulfinate (R)-2
was obtained by recrystallization from acetone: Rf ) 0.51
D
1.44, 1.52 (4s, 12H), 1.23-1.31 (m, 18H), 2.76-3.01 (m, 1H),
3.92-4.12 (m, 4H), 4.21 (dd, J ) 2.8, 8.0 Hz, 1H), 4.34 (ddd, J
) 8.0, 5.5, 5.5 Hz, 1H), 4.61 (d, J ) 3.7 Hz, 1H), 4.85 (d, J )
2.8 Hz, 1H), 5.81 (d, J ) 3.7 Hz, 1H), 7.10 (s, 2H); 13C NMR δ
23.7, 24.1, 24.6, 25.3, 26.2, 26.8, 26.9, 28.2, 34.4, 67.1, 72,0,
80.3, 80.9, 83.2, 105.0, 109.4, 112.4, 122.9, 137.6, 148.9, 153.3;
IR (neat) 2950, 1595, 1455, 1370, 1210, 1120, 1070, 1020 cm-1
;
MS (EI) m/ e 510 (M+, 4), 495 (67), 187 (45), 163 (53), 151 (76),
129 (95), 100 (66), 85 (100). Anal. Calcd for C27H42O7S: C,
63.50; H, 8.29. Found: C, 63.29; H, 8.50.
(S)-(-)-3,5-Di-ter t-bu tyl-4-m eth oxyp h en yl Meth yl Su l-
foxid e ((S)-9). To a solution of the sulfinate (R)-2 (1.09 g,
2.58 mmol) in a mixed solvent of Et2O (4 mL) and THF (1.6
mL) was added dropwise a solution of MeMgI (6.44 mmol) in
Et2O (5 mL) at 0 °C over a period of 3 min. The reaction
mixture was allowed to warm to room temparature and stirred
for 10 min. The mixture was then quenched with saturated
NH4Cl (5 mL) at 0 °C and concentrated under reduced
pressure. The aqueous mixture was extracted with AcOEt.
The combined organic extracts were washed with brine (5 mL),
dried over Na2SO4, and concentrated to give the crude sulfox-
ide, which was purified by column chromatography (silica gel,
hexane/ethyl acetate ) 5/5) to give the sulfoxide (S)-9 (678 mg,
93%) as a colorless solid: Rf ) 0.29 (hexane/ethyl acetate )
(hexane/ethyl acetate ) 9/1); mp 138-139 °C; [R]20 ) +50.4
D
(c 0.40, acetone); 1H NMR δ 0.70-1.80 (m, 7H), 0.83-0.95 (m,
9H), 1.44 (s, 18H), 2.04-2.30 (m, 2H), 3.71 (s, 3H), 4.19 (dt, J
) 4.5, 10.7 Hz, 1H), 7.58 (s, 2H); 13C NMR δ 15.5, 20.8, 21.9,
22.9, 25.4, 31.7, 33.9, 36.1, 43.5, 48.1, 64.5, 82.2, 123.0, 139.4,
144.9, 162.7; IR (KBr) 2925, 1445, 1390, 1215, 1110 cm-1; MS
(EI) m/ e 422 (M+, 0.3), 407 (2), 284 (100), 269 (77). Anal. Calcd
for C25H42O3S: C, 71.04; H, 10.02. Found: C, 71.03; H, 10.22.
Dia ceton e D-Glu cose 2,4,6-Tr iisop r op ylben zen esu lfi-
n a te Ester (3). The sulfonyl chloride 1116 (25.0 g, 82.5 mmol)
was added portionwise to a vigorously stirred suspension of
zinc powder (12.5 g, 191 mmol) in hot water (120 mL, 70-75
°C). The suspension was allowed to warm to 90 °C and stirred
for 1 h. To the cooled suspension was added 12 mol/L NaOH
(8 mL) and then solid Na2CO3 (ca. 10 g) was added to make
the mixture strongly basic. The suspension was filtered
through Celite 500 and precipitates were washed with hot
water (50 mL). The filtrate was concentrated on the hot plate
to half volume. Then the solution was cooled to 0 °C to give
colorless crystals which were filtered, washed with water (30
mL), and dried in an oven at 50 °C under reduced pressure.
The dried solid was dissolved in EtOH, and the insoluble solid
was removed by filtration. The filtrate was evaporated and
5/5); mp 111-112 °C; [R]19 ) -94.5 (c 0.346, acetone); CD
D
(2,2,4-trimethylpentane) 251 ([θ] -7.71 × 104) and 222 ([θ]
1
+1.22 × 105) nm; H NMR δ 1.45 (s, 18H), 2.72 (s, 3H), 3.72
(s, 3H), 7.51 (s, 2H); 13C NMR δ 31.8, 36.2, 43.7, 64.4, 121.9,
138.6, 145.4, 161.9; IR (KBr) 2950, 1450, 1210, 1110, 1040,
1010 cm-1; MS (EI) m/ e 282 (M+, 57), 267 (100), 252 (8), 237
(14). Anal. Calcd for C16H26O2S: C, 68.04; H, 9.28. Found:
C, 67.81; H, 9.51.
(R)-(+)-Meth yl 2,4,6-Tr iisopr opylph en yl Su lfoxide ((R)-
13). The reaction was carried out as described above using
the sulfinate (S)-3 (1.27 g, 2.49 mmol) to give the sulfoxide
(R)-13 (620 mg, 94%) as a colorless solid: Rf ) 0.20 (hexane/