The Journal of Organic Chemistry
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THF and a 0.5 M THF solution of 2-methylallylMgCl (1.10 mL, 0.54
mmol) were used. The resulting crude residue was purified by flash
chromatography (silica gel, hexane/EtOAc 7:3) to obtain 11d (35 mg,
55%): [α]2D0 −8.7 (c = 1.1, CHCl3); IR (film) 3448, 3062, 3030, 2987,
C22H27NO5NaS, 440.1502; found, 440.1502. (b) Following the
general procedures, 50 mg (0.15 mmol) of isoxazolidine 8, 1.50 mL
of THF, and 0.30 mL (0.45 mmol) of a 1.5 M THF solution of
BnMgCl were used, affording 11g (26 mg, 42%).
(1′R,2R,3S,4R)-2-[(1′-Phenylsulfonyl)(3′-(4-methoxyphenyl))-
propyl]-1-hydroxy-3,4-isopropylidenedioxypyrrolidine (11h). (a)
Following the general procedures, isoxazolidine 7 (150 mg, 0.45
mmol) in 4.50 mL of THF and a 0.25 M THF solution of p-
MeOC6H4CH2MgCl (5.40 mL, 1.35 mmol) were used. The resulting
crude residue was purified by flash chromatography (silica gel, hexane/
EtOAc 7:3) to obtain 11h (83 mg, 42%): [α]2D0 −5.2 (c = 1.4, CHCl3);
IR (film) 3456, 2989, 1610, 1512, 14461, 1301, 1247, 1033, 864 cm−1;
1H NMR (200 MHz, CDCl3) δ 8.00 (2H, d, J = 8.2 Hz), 7.71−7.52
(3H, m), 6.98 (2H, d, J = 6.2 Hz), 6.77 (2H, d, J = 6.2 Hz), 5.26 (1H,
bs), 4.74 (1H, dd, J = 6.2 and 6.0 Hz), 4.46 (1H, t, J = 6.0 Hz), 3.77
(3H, s), 3.66 (1H, dd, J = 6.2 and 11.6 Hz), 3.48−3.37 (1H, m), 3.10
(1H, t, J = 6.6 Hz,), 2.92 (1H, dd, J = 6.2 and 11.6 Hz), 2.66 (2H, t, J =
8.4 Hz), 2.16−2.02 (2H, m), 1.50 (3H, s), 1.31 (3H, s); 13C NMR (50
MHz, CDCl3) δ 158.3, 138.3, 134.1, 132.4, 129.6, 129.5, 129.3, 129.1,
126.8, 114.2, 81.8, 77.3, 72.3, 62.9, 55.5, 32.3, 28.1, 27.5, 25.2; HRMS
(EI) calcd for C23H29NO6NaS, 470.1607; found, 470.1614. (b)
Following the general procedures, 50 mg (0.15 mmol) of isoxazolidine
8, 1.90 mL of THF, and 1.80 mL (0.45 mmol) of a 0.25 M THF
solution of p-MeOC6H4CH2MgCl were used, affording 11h (27 mg,
40%).
( 1 ′ R , 2 R , 3 S , 4 R ) - 2 - [ ( 1 ′ - P h e n y l s u l f o n y l ) ( 2 ′ - ( 2 -
propynyloxytetrahydropirane))ethyl]-1-hydroxy-3,4-isopropylidene-
dioxypyrrolidine (11i). (a) To a stirred solution of 2-propynylloxyte-
trahydropirane (75 μL, 0.54 mmol) in THF (1.50 mL) was slowly
added a 1.6 M hexane solution of n-BuLi (0.30 mL, 0.50 mmol), and
the mixture was reacted at 0 °C for 10 min. The reaction was added to
a solution of isoxazolidine 8 (60 mg, 0.18 mmol) in 1.50 mL of THF,
and the mixture was stirred at 0 °C for 1 h. The reaction was allowed
to warm slowly to room temperature, quenched with a saturated
aqueous solution of NH4Cl, and the product was extracted with DCM
(3 × 15 mL). The combined organic layers were washed with brine,
dried (Na2SO4), filtered, and concentrated in vacuo. The resulting
crude residue was purified by flash chromatography (silica gel, hexane/
EtOAc 7:3) to obtain 11i (33 mg, 40%): [α]2D0 −22.3 (c = 0.6,
CHCl3); IR (film) 3410, 2937, 2854, 1448, 1375, 1149, 731, 721 cm−1;
1H NMR (200 MHz, CDCl3) δ 7.98 (2H, d, J = 8.0 Hz), 7.68−7.54
1
2935, 1663, 1496, 1448, 1029, 734, 596 cm−1; H NMR (200 MHz,
CDCl3) δ 8.01 (2H, d, J = 7.8 Hz), 7.67−7.53 (3H, m), 5.59 (1H, bs),
4.79−4.72 (1H, m), 4.75 (1H, s), 4.64−4.57 (1H, m), 4.60 (1H, s),
3.70 (1H, dd, J = 5.4 and 11.6 Hz), 3.50 (1H, dt, J = 5.0 and 6.8 Hz),
3.14 (1H, t, J = 5.6 Hz), 2.98 (1H, dd, J = 5.0 and 11.6 Hz), 2.10−1.95
(2H, m), 1.95−1.92 (2H, m), 1.47 (3H, s), 1.55 (3H, s), 1.30 (3H, s);
13C NMR (50 MHz, CDCl3) δ 138.4, 134.1, 129.5, 129.3, 144.2, 112.1,
114.8, 82.3, 77.3, 72.5, 63.6, 62.9, 35.3, 27.5, 24.8, 25.2, 22.0; HRMS
(EI) calcd for C19H28NO5S, 382.1682; found, 382.1699. (b) Following
the general procedures, 61 mg (0.19 mmol) of isoxazolidine 8, 1.90
mL of THF, and 1.12 mL (0.56 mmol) of a 0.5 M THF solution of 2-
methylallylMgCl were used, affording 11d (40 mg, 55%).
(1′R,2R,3S,4R)-2-[(1′-Phenylsulfonyl)(2′-phenyl)ethyl]-1-hydroxy-
3,4-isopropylidenedioxypyrrolidine (11e). (a) Following the general
procedures, isoxazolidine 7 (88 mg, 0.27 mmol) in 2.70 mL of THF
and a 2.8 M Et2O solution of PhMgBr (0.30 mL, 0.81 mmol) were
used. The resulting crude residue was purified by flash chromatog-
raphy (silica gel, hexane/EtOAc 7:3) to obtain 11e (54 mg, 50%):
[α]2D0 −3.2 (c = 1.7, CHCl3); IR (film) 3448, 3062, 3030, 2987, 2935,
1663, 1496, 1448, 1029, 734, 596 cm−1; 1H NMR (200 MHz, CDCl3)
δ 7.95 (2H, d, J = 7.8 Hz), 7.64−7.48 (3H, m), 7.26−7.06 (5H, m),
4.71−4.73 (2H, m), 3.83 (1H, dd, J = 6.0 and 11.2 Hz), 3.40−3.42
(1H, dd, J = 6.0 and 11.0 Hz), 3.25 (1H, t, J = 5.4 Hz, H-2), 3.15 (2H,
d, J = 6.0 Hz, CH2-2′), 2.95 (1H, dd, J = 5.0 and 11.0 Hz), 1.34 (3H,
s), 1.26 (3H, s); 13C NMR (50 MHz, CDCl3) δ 138.5, 137.9, 134.1,
129.4, 129.2, 128.8, 126.9, 114.4, 81.4, 77.3, 71.9, 65.9, 62.7, 32.9, 27.4,
25.4; HRMS (EI) calcd for C21H25NO5NaS, 426.1345; found,
426.1342. (b) Following the general procedures, 60 mg (0.18
mmol) of isoxazolidine 8, 1.80 mL of THF, and 0.20 mL (0.54
mmol) of a 2.8 M Et2O solution of PhMgBr were used, affording 11e
(38 mg, 52%).
(1′R,2R,3S,4R)-2-[(1′-Phenylsulfonyl)(2′-(4-fluorophenyl))ethyl]-1-
hydroxy-3,4-isopropylidenedioxypyrrolidine (11f). (a) Following the
general procedures, isoxazolidine 7 (100 mg, 0.30 mmol) in 3 mL of
THF and a 0.8 M THF solution of p-FC6H4MgCl (1.15 mL, 0.90
mmol) were used. The resulting crude residue was purified by flash
chromatography (silica gel, hexane/EtOAc 7:3) to obtain 11f (60 mg,
48%): [α]2D0 −8.7 (c = 0.4, CHCl3); IR (film) 3423, 3066, 2987, 2926,
1
2868, 1600, 1508, 1375, 1249, 1157, 1024, 864 cm−1; H NMR (600
MHz, CDCl3) δ 7.88 (2H, d, J = 8.0 Hz), 7.58 (1H, t, J = 8.0 Hz), 7.47
(2H, t, J = 8.0 Hz), 6.97−6.94 (2H, m), 6.85−6.80 (2H, m), 5.45 (1H,
bs), 4.68−4.58 (1H, m), 4.57 (1H, t, J = 5.8 Hz), 3.72−3.68 (1H, m),
3.64 (1H, dd, J = 6.0 and 11.8 Hz), 3.12 (1H, t, J = 5.4 Hz), 3.10 (1H,
d, J = 6.2 Hz), 3.08 (1H, d, J = 6.2 Hz), 2.90 (1H, dd, J = 5.4 and 11.8
Hz), 1.29 (3H, s), 1.20 (3H, s); 13C NMR (50 MHz, CDCl3) δ 162.8,
160.4, 138.3, 133.9, 133.4, 130.6, 129.2, 128.7, 115.2, 114.3, 81.3, 77.9,
71.9, 66.0, 62.6, 32.0, 27.2, 25.1; HRMS (EI) calcd for
C21H24NO5FNaS, 444.1251; found, 444.1261. (b) Following the
general procedures, 58 mg (0.18 mmol) of isoxazolidine 8, 1.80 mL of
THF, and 0.67 mL (0.54 mmol) of a 0.8 M THF solution of p-
FC6H4MgCl were used, affording 11f (38 mg, 50%).
(3H, m), 5.85 (1H, bs), 4.99−4.95 (1H, m), 4.91−4.75 (4H, m),
4.03−3.34 (7H, m), 3.05 (1H, dd, J = 5.2 and 11.8 Hz), 2.87−2.80
(2H, m), 1.75−1.54 (4H, m), 1.48 (3H, s), 1.32 (3H, s); 13C NMR
(50 MHz, CDCl3) δ 138.1, 134.6, 129.8, 129.3, 112.7, 97.1, 82.2, 81.9,
79.9, 79.8, 77.3, 63.7, 63.1, 62.2, 54.6, 30.4, 29.9, 27.5, 25.5, 25.4, 19.2;
HRMS (EI) calcd for C23H31NO7NaS, 488.1713; found, 488.1715.
(1′R,3S,4R)-3,4-Isopropylidenedioxy-5-[(1′-phenylsulfonyl)(2′-
phenyl)ethyl]-3,4-dihydro-2H-pyrrole 1-Oxide (12). To a stirred
solution of hydroxylamine 11e (71 mg, 0.18 mmol) in 1 mL of DCM
at 0 °C was added 30 mg (0.27 mmol) of activated MnO2 (90%
purity). The resulting dispersion was stirred for 2 h at rt, filtered
through a short pad of Celite and Na2SO4, and concentrated in vacuo.
The resulting crude residue was purified by flash chromatography
(silica gel, hexane/EtOAc 3:7) to obtain 12 (69 mg, 92%): [α]2D0 +35.6
(c = 0.3, CHCl3); IR (film) 2978, 2937, 1577, 1560, 1375, 1209, 1085,
(1′R,2R,3S,4R)-2-[(1′-Phenylsulfonyl)(3′-phenyl)propyl]-1-hy-
droxy-3,4-isopropylidenedioxypyrrolidine (11g). (a) Following the
general procedures, isoxazolidine 7 (80 mg, 0.30 mmol) in 3 mL of
THF and a 1.5 M THF solution of BnMgCl (0.60 mL, 0.90 mmol)
were used. The resulting crude residue was purified by flash
chromatography (silica gel, hexane/EtOAc 7:3) to obtain 11g (50
mg, 45%): [α]2D0 −7.8 (c = 1.4, CHCl3); IR (film) 3448, 3062, 2987,
1
688 cm−1; H NMR (200 MHz, CDCl3) δ 8.00 (2H, d, J = 8.0 Hz),
1
2937, 2862, 1558, 1442, 1305, 1085, 864 cm−1; H NMR (200 MHz,
7.65−7.53 (3H, m), 7.27−7.11 (5H, m), 5.15 (1H, d, J = 6.8 Hz), 4.87
(1H, dt, J = 6.8 and 12.0 Hz), 4.74−4.67 (1H, m), 3.96 (2H, bs), 3.80
(1H, dd, J = 12.2 and 14 Hz), 3.36 (1H, dd, J = 4.2 and 14 Hz), 1.30
(3H, s), 1.17 (3H, s); 13C NMR (50 MHz, CDCl3) δ 139.1, 135.9,
135.8, 134.4, 129.4, 129.1, 128.6, 128.3, 127.4, 112.9, 81.0, 71.3, 68.3,
64.4, 30.6, 26.2, 25.5; HRMS (EI) calcd for C21H23NO5NaS, 424.1189;
found, 424.1184.
CDCl3) δ 7.98 (2H, d, J = 7.8 Hz), 7.68−7.52 (3H, m), 7.26−7.06
(5H, m), 5.15 (1H, bs), 4.77−4.68 (1H, m), 4.45 (1H, t, J = 6.2 Hz),
3.65 (1H, dd, J = 6.0 and 11.8 Hz), 3.50−3.41 (1H, m), 3.11 (1H, t, J
= 6.2 Hz), 2.94 (1H, dd, J = 6.0 and 11.8 Hz), 2.77−2.60 (2H, m),
2.25−2.04 (2H, m), 1.50 (3H, s), 1.31 (3H, s); 13C NMR (50 MHz,
CDCl3) δ 140.6, 138.2, 134.0, 129.5, 129.1, 128.7, 128.9, 126.6, 114.8,
81.8, 77.3, 73.1, 71.9, 62.9, 33.2, 28.1, 27.4, 25.2; HRMS (EI) calcd for
7073
dx.doi.org/10.1021/jo400873c | J. Org. Chem. 2013, 78, 7068−7075