Khiar et al.
JOCArticle
(2.4 g, 21.14 mmol) dropwise at room temperature. The reaction
mixture was stirred overnight, washed with water, and extracted
three times with EtOAc. The combined organics were washed
with saturated NaHCO3 solution and brine, filtered, and eva-
porated. The crude product was purified by silica gel chroma-
tography, using 1:2 EtOAc/hexanes, affording 2.22 g (73%) of
δ 3.33 (t, 2H, J = 6.5 Hz), 2.74-2.63 (m, 2H), 2.55 (s, 3H), 1.88-
1.79 (m, 2H), 1.77-1.69 (m, 2H); 13C NMR (125 MHz, CDCl3)
δ 53.9, 50.9, 38.6, 28.0, 20.0; HRMS m/e calcd for C5H11N3OS
(M þ H)þ 162.0701, found 162.0698.
(R)-(-)-1-(4-Azidobutylsulfinyl)Pentane (25-RS): In a round-
bottomed flask flushed with argon was placed anhydrous
magnesium (17.91 mg, 0.74 mmol), which was covered with
Et2O (0.5 mL), then 1-bromopentane (0.1 mL, 0.74 mmol) was
added drop by drop while maintaining the reflux of the solution
affording a solution of the Grignard reagent. In a second round-
bottomed flask under argon atmosphere was placed the sulfi-
nate ester 23-SS (250 mg, 0.61 mmol) in toluene (10 mL) and the
solution was cooled to 0 °C. Then the Grignard reagent was
added to the solution of the sulfinate ester through the cannula
and the mixture was stirred 1 h at 0 °C. Neutralization was then
carried out with a saturated solution of aqueous NH4Cl. The
aqueous layer was extracted with CH2Cl2 and the resulting
organic layers were combined, dried on Na2SO4, and concen-
trated. Column chromatography of the residue gave the sulf-
oxide 25-RS (117,7 mg, 88%) as a colorless liquid. Rf 0.13
(EtOAc/CH2Cl2, 1: 4); [R]D -7,17 (c 1, CHCl3); 1H NMR
(500 MHz, CDCl3) δ 3.41-3.33 (m, 2H), 2.75-2.61 (m, 4H),
1.93-1.87 (m, 2H), 1.84-1.73 (m, 4H), 1.51-1.36 (m, 4H), 0.93
(t, J = 7.5 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 52.6, 51.7,
50.9, 30.9, 28.1, 22.3, 20.1, 13.8; HRMS m/e calcd for
C9H20N3OS (M þ H)þ 218.1327, found 218.1333.
1
20 as a colorless oil; Rf 0.65 (EtOAc/hexanes, 1:2); H NMR
(500 MHz, CDCl3) δ 3.35-3.29 (m, 2H), 2.94-2.90 (m, 2H),
2.36 (s, 3H, CH3), 1.71-1.66 (m, 4H); 13C NMR (125 MHz,
CDCl3) δ 50.8, 30.6, 28.4, 27.8, 26.8.
4-Azidobutane-1-sulfinyl chloride (21): To a solution of com-
pound 20 (2.22 g, 12.83 mmol) in methylene chloride (42 mL) at
-20 °C was added acetic anhydride (1.2 mL, 12.83 mmol) and
sulfuryl chloride (2 mL, 25.66 mmol). The resulting mixture was
stirred for 1 h at -5 °C and then the solvent was evaporated and
the residue was dried under vacuum. The crude sulfinyl chloride,
which was kept under argon, was used immediately for the
preparation of sulfinate ester.
(S)-(1,2:5,6-Di-O-isopropylidene-r-D-glucofuranosyl) 4-azido-
butanesulfinate (23-SS): To a solution of 1,2:5,6-di-O-isopropyli-
dene-R-D-glucofuranose (DAG) 22 (1.66 g, 6.41 mmol) and
Hunig’s base (4.4 mL) in anhydrous toluene, cooled to -78 °C
and placed under argon atmosphere, was added 4-azidobutyl-
1-sulfinyl chloride 21 (7.67 mmol) while the reaction mixture was
being vigorously stirred. After the solution was stirred at -78 °C
for 4 h, 1 M HCl was added, the reaction mixture was extracted
with CH2Cl2, the organic layers were successively washed with
saturated NaHCO3 solution and brine, and after drying on
Na2SO4, the solvent was removed under vacuum affording the
sufinate esters in 95% yield. Analysis of the crude mixture in
deuterated benzene revealed a diastereomeric ratio of 97:3. Pure
samples of individual diastereomers were obtained by silica gel
column chromatography by using 2-propanol/hexanes (1:20) as
elutant, affording 23-SS (1.9 g, 73%) as the major diastereomer.
Enough quantity of the minor diasteroisomer was obtained for
analysis by repeating the reaction several times.
For the major diastereomer 23-SS: Rf 0.18 (hexanes/2-propa-
nol, 20:1); [R]D -55 (c 1.05, CHCl3); 1H NMR (500 MHz, C6D6)
δ 5.92 (d, 1H, J = 3.6 Hz), 4.94 (d, 1H, J = 2.75 Hz), 4.61 (d, 1H,
J = 3.65 Hz), 4.59-4.53 (m, 2H, H-4 and H-5), 4.26 (dd, 1H,
J = 8.5 Hz, J = 5.2 Hz), 4.20 (dd, 1H, J = 8.4 Hz, J = 6.1 Hz),
2.62 (t, 2H, J = 6.75 Hz), 2.34 (t, 2H, J = 7.3 Hz), 1.51(s, 3H),
1.46 (s, 3H), 1.44-1.36 (m, 2H), 1.41(s, 3H), 1.18(s, 3H), 1.15-
1.09 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 112.4, 109.2,
104.9, 83.5, 80.3, 79.3, 72.3, 66.8, 65.5, 50.8, 28.0, 26.7, 26.6,
26.2, 25.2, 18.6; HRMS m/e calcd for C16H27N3O7S (M þ H)þ
406.1648, found 406.1649.
For the minor diastereomer 23-RS: Rf 0.24 (hexanes/2-pro-
panol, 20:1); [R]D -5.6 (c 1, CHCl3); 1H NMR (400 MHz,
CDCl3) δ 5.96 (d, 1H, J = 3.2 Hz, H-1), 5.04 (d, 1H, J = 3.8 Hz),
4.95 (d, 1H, J = 2.76 Hz), 4.50 (dd, 1H, J = 2.8 Hz, J = 8.5 Hz),
4.40-4.32 (m, 1H), 4.17 (dd, 1H, J = 4.5 Hz, J = 8.9 Hz), 4.10
(dd, 1H, J = 6.1 Hz, J = 8.9 Hz), 2.63 (t, 2H, J = 6.8 Hz), 2.54-
2.39 (m, 2H), 1.45 (s, 3H), 1.44 (s, 3H), 1.33 (s, 3H), 1.18-1.15
(m, 2H), 1,09 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 112.4,
109.4, 105.3, 83.8, 83.1, 80.8, 72.1, 67.7, 57.0, 56.5, 50.8, 28.0,
26.9, 26.7, 26.1, 25.2, 18.4.
(R)-(-)-(4-azidobutylsulfinyl)cyclohexane (26-RS): Sulfinate
ester 23-SS (300 mg, 0.735 mmol) was dissolved in anhydrous
toluene (12 mL). After the mixture was cooled to 0 °C, 2 M
cyclohexylmagnesium chloride (0.15 mL, 0.95 mmol) was
added, then the reaction mixture stirred for 1 h. Neutralization
was then carried out with a saturated solution of aqueous
NH4Cl. The aqueous layer was extracted with CH2Cl2 and the
resulting organic layers were combined, dried on Na2SO4, and
concentrated. Column chromatography of the residue gave the
sulfoxide 26-RS (100 mg, 59%) as a colorless liquid. Rf 0.15
(EtOAc/DCM, 1:4); [R]D -31.7 (c 1.2, CHCl3); 1H NMR (500
MHz, CDCl3) δ 3.42-3.33 (m, 2H), 2.72-2.63 (m, 2H), 2.60-
2.54 (m, 1H), 2.14 (d, 1H, J = 13 Hz), 1.97-1.69 (m, 9H), 1.55-
1.25 (m, 6H); 13C NMR (125 MHz, CDCl3) δ 59.1, 50.9, 48.2,
28.1, 26.4, 25.5, 25.4, 25.1, 24.9, 20.3; HRMS m/e calcd for
C10H19N3OS (M þ H)þ 230.1327, found 230.1326.
(R)-(-)-2-(4-Azidobutylsulfinyl)naphthalene (27-RS): The
Grignard reagent was freshly prepared as follows: In a round-
bottomed flask flushed with argon was placed anhydrous
magnesium (243.1 mg, 10 mmol), which was covered with
Et2O (8.18 mL), then 1-bromonaphthalene (1.39 mL, 10 mmol)
was added drop by drop while maintaining the reflux of the
mixture.
In a second flask under argon atmosphere, a solution of
sulfinate ester 23-SS (250 mg, 0.61 mmol) in toluene (10 mL)
was cooled to 0 °C. The 1-naphthylmagnesium chloride (0.6 mL)
was added to a sulfinate solution through a cannula and stirred
1 h at 0 °C. Neutralization was then carried out with a saturated
solution of aqueous NH4Cl. The aqueous layer was extracted
with CH2Cl2 and the resulting organic layers were combined,
dried on Na2SO4 ,and concentrated. Chromatography of the
residue gave the sulfoxide 27-RS (69 mg, 43%) as a colorless
liquid. Rf 0.34 (EtOAc/hexanes, 1:1); [R]D -367.65 (c 0.9,
CHCl3); 1H NMR (500 MHz, CDCl3) δ 8.15 (dd, 1H, J =
1 Hz, J = 7.5 Hz), 8.01-7.94 (m, 3H), 7.69 (dd, 1H, J = 7.5 Hz,
J = 8.5 Hz), 7.64-7.59 (m, 2H), 3.35-3.26 (m, 2H), 3.11-2.84
(m, 2H), 2.04-1.95-171 (m, 2H), 1.82-1.77 (m, 2H); 13C NMR
(125 MHz, CDCl3) δ 139.2, 133.5, 131.2, 129.1, 128.8, 127.3,
126.7, 125.6, 123.1, 121.4, 54.9, 50.9, 28.0, 19.8; HRMS m/e
calcd for C14H15N3OS (M þ H)þ 274.1014, found 274.1016.
(R)-(-)-11-(4-Azidobutylsulfinyl)Undec-1-ene (28-RS): Sulfi-
nate ester 23-SS (323 mg, 0.792 mmol) was dissolved in
(R)-(-)-1-Azido-4-(methylsulfinyl)butane (24-RS): Sulfinate
ester 23-SS (345 mg, 0.85 mmol) was dissolved in anhydrous
toluene (14 mL). After the mixture was cooled to 0 °C, methyl
magnesium chloride (0.36 mL, 5 mmol) was added and the
solution was stirred for 1 h at 0 °C. The mixture was then
neutralized with a saturated solution of aqueous NH4Cl. The
aqueous layer was extracted with CH2Cl2 and the resulting
organic layers were combined, dried on Na2SO4, and concen-
trated. Chromatography of the residue gave the sulfoxide 24-RS
(127 mg, 93%) as a colorless liquid. Rf 0.31 (EtOAc/MeOH,
9:1); [R]D -81,53 (c 0.16, CHCl3); 1H NMR (500 MHz, CDCl3)
J. Org. Chem. Vol. 74, No. 16, 2009 6007