7802 J . Org. Chem., Vol. 66, No. 23, 2001
Boto et al.
together with 2-hydroxy-3-iodo derivatives 9a (26 mg, 0.08
mmol, 12%) and 9b (6 mg, 0.02 mmol, 3%) (59% overall yield).
Compound 10a : two rotamers at 26 °C (1.4:1); one rotamer
at 70 °C; syrup; [R]D +3 (c ) 0.61); IR 1740, 1714, 1450, 1385
(11) 166 (100); HRMS calcd for C14H21NO4 267.1471, found
267.1475. Anal. Calcd for C14H21NO4: C, 62.90; H, 7.92; N,
5.24. Found: C, 62.76; H, 8.14; N, 5.24.
Met h yl
(2S,3S,4S)-4-Acet yloxy-2-a llyl-3-iod o-1-p yr -
1
cm-1; H NMR (500 MHz, 70 °C) δ 5.46 (1H, br s), 5.34 (1H,
r olid in eca r b oxyla t e (13a ) a n d Met h yl (2R,3R,4S)-4-
Acetyloxy-2-a llyl-3-iod o-1-p yr r olid in eca r boxyla te (13b).
A solution of the acid 8 (106 mg, 0.46 mmol) in acetonitrile
(12 mL) was treated with DIB (297 mg, 0.96 mmol) and iodine
(130 mg, 0.5 mmol) under nitrogen. After stirring at room
temperature for 3.5 h, the reaction was cooled at 0 °C, and an
excess of allyltrimethylsilane was added (0.7 mL, 4.6 mmol).
Then, BF3‚Et2O (0.18 mL, 0.96 mmol) was added dropwise.
The reaction mixture was allowed to reach room temperature
(1 h) and stirred for other 2 h. The solution was poured into
saturated sodium bicarbonate and extracted with dichlo-
romethane. The organic layer was washed with 10% aqueous
sodium thiosulfate and brine, dried (Na2SO4), and evaporated
under vacuum. Column chromatography on silica gel (hex-
anes-EtOAc, 90:10) afforded allyl derivatives 13a (60 mg, 0.17
mmol, 37%) and 13b (6 mg, 0.017 mmol, 4%) (41% global yield,
13a :13b, 10:1). Compound 13a : two rotamers at 26 °C (1.5:
1); one rotamer at 70 °C; oil; [R]D +10 (c ) 0.71); IR 1744, 1697,
1454, 1385, 1123 cm-1; 1H NMR (500 MHz, 70 °C) δ 5.80 (1H,
m), 5.38 (1H, ddd, J ) 5.1, 2.3, 2.3 Hz), 5.15 (1H, d, J ) 10.3
Hz), 5.10 (1H, dd, J ) 17.1, 1.5 Hz), 4.34 (1H, m), 4.27 (1H, d,
J ) 2.1 Hz), 4.21 (1H, dd, J ) 12.7, 5.8 Hz), 3.75 (3H, s), 3.48
(1H, dd, J ) 12.7, 2.1 Hz), 2.67 (1H, m), 2.38 (1H, ddd, J )
14.4, 8.8, 8.5 Hz), 2.07 (3H, s); 13C NMR (125.7 MHz, 26 °C) δ
major rotamer 169.5 (C), 155.0 (C), 133.5 (CH), 118.5 (CH2),
80.3 (CH), 68.2 (CH), 52.7 (CH3), 50.0 (CH2), 38.5 (CH2), 23.5
(CH), 20.8 (CH3); δ minor rotamer 169.5 (C), 155.0 (C), 133.7
(CH), 118.6 (CH2), 79.5 (CH), 68.2 (CH), 52.7 (CH3), 50.4 (CH2),
39.2 (CH2), 24.5 (CH), 20.8 (CH3); MS (EI) m/z (rel intensity)
312 (M+ - C3H5, 19), 252 (60), 125 (100); HRMS calcd for
dd, J ) 6.0, 1.8 Hz), 4.23 (1H, s), 4.16 (1H, dd, J ) 12.6, 6.0
Hz), 3.78 (3H, s), 3.57 (1H, dd, J ) 12.6, 1.7 Hz), 3.44 (3H, s),
2.06 (3H, s); 13C NMR (125.7 MHz, 70 °C) δ 170.0 (C), 155.7
(C), 97.3 (CH), 79.4 (CH), 56.6 (CH3), 52.9 (CH3), 50.3 (CH2),
24.9 (CH), 20.7 (CH3); MS (EI) m/z (rel intensity) 312 (M+
OMe, 29), 284 (9), 252 (33), 156 (100), 125 (94); HRMS calcd
for C8H11INO4 311.9733, found 311.9744. Anal. Calcd for C9H14
-
-
INO5: C, 31.50; H, 4.11; N, 4.08. Found: C, 31.55; H, 4.29; N,
4.03. Compound 10b: two rotamers at 26 °C (1.6:1); one
rotamer at 70 °C; syrup; [R]D -22 (c ) 0.42); IR 1748, 1711,
1450, 1387, 1258 cm-1; 1H NMR (500 MHz, 70 °C) δ 5.45 (1H,
br s), 4.72 (1H, ddd, J ) 7.6, 7.5, 5.0 Hz), 4.55 (1H, d, J ) 5
Hz), 3.78 (3H, s), 3.73 (1H, dd, J ) 10.8, 7.5 Hz), 3.5 (1H, m),
3.45 (3H, s), 2.11 (3H, s); 13C NMR (125.7 MHz, 26 °C) δ major
rotamer 169.9 (C), 155.9 (C), 95.9 (CH), 70.8 (CH), 56.8 (CH3),
53.0 (CH3), 47.6 (CH2), 30.8 (CH), 20.9 (CH3); δ minor rotamer
169.9 (C), 155.9 (C), 95.7 (CH), 70.2 (CH), 56.3 (CH3), 53.0
(CH3), 47.8 (CH2), 31.5 (CH), 20.9 (CH3); MS (EI) m/z (rel
intensity) 312 (M+ - OMe, 21), 284 (12), 252 (13), 156 (100);
HRMS calcd for C8H11INO4 311.9733, found 311.9730. Anal.
Calcd for C9H14INO5: C, 31.50; H, 4.11; N, 4.08. Found: C,
31.82; H, 3.79; N, 3.91.
Met h yl (2S,3R,4R)-4-Acet yloxy-3-a llyl-2-m et h oxy-1-
p yr r olid in eca r boxyla te (11). A solution of 3-iodo-2-methoxy-
1-pyrrolidine derivative 10a (90 mg, 0.26 mmol) and a catalytic
amount of AIBN (10 mg) in dry benzene (7 mL), under
nitrogen, was treated with allyltributyltin (0.26 mL, 1.23
mmol) at room temperature. Then the reaction was heated to
80 °C for 4 h. The reaction mixture was allowed to cool to room
temperature, the solvent was evaporated under vacuum, and
the residue was purified by column chromatography (first
elution with hexanes to remove the tin reagent and then with
hexanes-EtOAc, 4:1), yielding 11 (61 mg, 91%): two rotamers
at 26 °C (2.1:1); one rotamer at 70 °C; syrup; [R]D +12 (c )
C8H11INO4 311.9733, found 311.9725. Anal. Calcd for C11H16
-
INO4: C, 37.41; H, 4.57; N, 3.97. Found: C, 37.51; H, 4.41; N,
3.91. Compound 13b: two rotamers at 26 °C (1.6:1); one
rotamer at 70 °C; oil; [R]D -13 (c ) 1.16); IR 1745, 1700, 1453,
1389 cm-1 1H NMR (500 MHz, 70 °C) δ 5.76 (1H, m), 5.16
;
1
0.318); IR 1732, 1707, 1451 cm-1; H NMR (500 MHz, 70 °C)
(1H, d, J ) 11.4 Hz), 5.15 (1H, d, J ) 15.3 Hz), 4.80 (1H, ddd,
J ) 5.2, 5.2, 5.2 Hz), 4.41 (1H, dd, J ) 4.7, 4.7 Hz), 4.32 (1H,
m), 3.74 (3H, s), 3.69 (1H, dd, J ) 11.7, 4.9 Hz), 3.60 (1H, dd,
J ) 11.7, 5.8 Hz), 2.53 (2H, m), 2.10 (3H, s); 13C NMR (125.7
MHz, 26 °C) δ major rotamer 169.9 (C), 154.9 (C), 132.4 (CH),
119.4 (CH2), 71.6 (CH), 66.1 (CH), 52.6 (CH3), 49.7 (CH2), 36.0
(CH2), 27.4 (CH), 21.1 (CH3); δ minor rotamer 169.9 (C), 155.0
(C), 133.4 (CH), 119.4 (CH2), 71.3 (CH), 65.8 (CH), 52.6 (CH3),
50.0 (CH2), 36.8 (CH2), 28.0 (CH), 21.1 (CH3); MS (EI) m/z (rel
intensity) 312 (M+ - C3H5, 100), 252 (M+ - C3H5 - AcOH, 4);
HRMS calcd for C8H11INO4 311.9733, found: 311.9729. Anal.
Calcd for C11H16INO4: C, 37.41; H, 4.57; N, 3.97. Found: C,
37.34; H, 4.20; N, 4.18.
δ 5.78 (1H, m), 5.09 (1H, dd, J ) 12.5, 1.2 Hz), 5.08 (1H, dd,
J ) 15.8, 1.3 Hz), 4.96 (1H, br s), 4.89 (1H, ddd, J ) 5.6, 2.8,
2.8 Hz), 3.95 (1H, dd, J ) 12.6, 6.3 Hz), 3.72 (3H, s), 3.41 (1H,
dd, J ) 12.6, 3.2 Hz), 3.36 (3H, s), 2.34 (1H, ddd, J ) 7.2, 7.6,
1.5 Hz), 2.13 (1H, m), 2.06 (1H, m), 2.03 (3H, s); 13C NMR
(125.7 MHz, 70 °C) δ 170.4 (C), 155.80 (C), 134.8 (CH), 117.5
(CH2), 92.9 (CH), 76.0 (CH), 55.9 (CH3), 52.5 (CH3), 51.1 (CH2),
50.2 (CH), 34.7 (CH2), 20.9 (CH3); MS (EI) m/z (rel intensity)
226 (M+ - OMe, 2), 197 (29), 166 (100); HRMS calcd for C11H16
-
NO4 226.1079, found 226.1014. Anal. Calcd for C12H19NO5: C,
56.02; H, 7.44; N, 5.44. Found: C, 55.89; H, 7.75; N, 5.45.
Meth yl (2S,3S,4R)-4-Acetyloxy-2,3-d ia llyl-1-p yr r olid i-
n eca r boxyla te (12). A solution of 3-allyl-2-methoxypyrroli-
dine derivative 11 (30 mg, 0.12 mmol) and allyltrimethylsilane
(0.1 mL, 0.6 mmol) in dry acetonitrile (3 mL) was cooled to 0
°C and treated dropwise with BF3‚Et2O (0.05 mL, 0.24 mmol).
The reaction mixture was allowed to warm to room temper-
ature and stirred for 18 h; then it was poured into saturated
aqueous sodium bicarbonate and extracted with dichlo-
romethane. The organic layer was dried, concentrated under
vacuum, and purified by column chromatography (hexanes-
EtOAc, 4:1), yielding 12 (31 mg, 99%): two rotamers at 26 °C
(2:1); one rotamer at 70 °C; syrup; [R]D + 29 (c ) 0.348); IR
1730, 1689, 1453, 1391 cm-1; 1H NMR (C6D6, 500 MHz, 70 °C)
δ 5.79 (1H, dddd, J ) 17.3, 10.1, 7.3, 7.3 Hz), 5.65 (1H, dddd,
J ) 17.3, 10.5, 7.0, 7.0 Hz), 5.10 (1H, dd, J ) 17.3, 0.8 Hz),
5.07 (1H, dd, J ) 10.0, 0.9 Hz), 5.0 (1H, dd, J ) 10.5, 1.1 Hz),
4.99 (1H, dd, J ) 17.5, 1.0 Hz), 4.94 (1H, ddd, J ) 5.9, 2.8, 2.5
Hz), 3.90 (1H, dd, J ) 12.5, 5.9 Hz), 3.83 (1H, m), 3.60 (3H, s),
3.46 (1H, dd, J ) 12.6, 2.1 Hz), 2.80 (1H, m), 2.53 (1H, ddd, J
) 13.7, 8.5, 8.4 Hz), 2.25 (1H, m), 1.96 (2H, m), 1.73 (3H, s);
13C NMR (125.7 MHz, 70 °C) δ 169.9 (C), 155.3 (C), 134.9 (CH),
134.8 (CH), 117.4 (2 × CH2), 76.7 (CH), 61.6 (CH), 52.2 (CH3),
51.4 (CH2), 46.9 (CH), 38.1 (CH2), 36.5 (CH2), 20.8 (CH3); MS
(EI) m/z (rel intensity) 267 (M+, <1), 236 (M+ - OCH3, 1), 226
3-Allyla tion of Meth yl (2S,3S,4S)-4-Acetyloxy-2-a llyl-
3-iod o-1-p yr r olid in eca r boxyla te (13a ). A solution of 2-allyl-
3-iodopyrrolidine derivative 13a (35 mg, 0.1 mmol) and a
catalytic amount of AIBN (5 mg) in dry benzene (4 mL), under
nitrogen, was treated with allyltributyltin (0.1 mL, 0.5 mmol)
at room temperature. The reaction mixture was heated to 80
°C for 4 h and then cooled to room temperature, the solvent
was evaporated under vacuum, and the residue was purified
by column chromatography (first elution with hexanes to
remove the tin reagent and then with hexanes-ΕtOAc, 5:1),
yielding 12 (23 mg, 99%), identical to previously described (vide
supra).
Met h yl (3R,3a S,7a S)-3-Acet yloxy-2,3,3a ,4,7,7a -h exa -
h yd r o-1H-in d ole-1-ca r boxyla te (14). To a solution of the
2,3-diallylpyrrolidine derivative 12 (13 mg, 0.05 mmol) in
dichloromethane (3 mL) was added a catalytic amount of
Grubbs’ catalyst [Cl2(Cy3P)2RudCHPh] (3 mg, 0.0036 mmol);
the reaction was refluxed for 8 h and then stirred at room
temperature overnight. The reaction mixture was evaporated
under vacuum and purified by chromatography on silica gel
(hexanes-EtOAc, 95:5), yielding bicyclic compound 14 (11 mg,
95%): syrup; [R]D +175 (c ) 0.5); IR 1736, 1699, 1454, 1358
cm-1; 1H NMR (500 MHz, 70 °C) δ 5.68 (2H, m), 4.90 (1H, ddd,