8342 J . Org. Chem., Vol. 66, No. 25, 2001
Ambrosi et al.
Electr op h ilic Oxir a n e Op en in g Rea ction . The general
procedure used for preparing trifluoro-derivatives 4 was
applied on oxiranes 14. The reactions lasted 5 days at 40 °C.
FC purification with n-hexane/ethyl acetate, 3:7 allowed the
isolation of the pure compounds 15.
J ) 48.8, 3.3, and 1.7 Hz, 1H), 7.34 and 7.56 (m, 4H); 19F NMR
(CDCl3) δ -192.35 (dddd, J ) 48.8, 45.8, 18.0, and 7.2 Hz).
13C NMR (CDCl3) δ 21.4, 23.4 (J C,F ) 22 Hz); 24.0, 30.9, 59.6,
68.9 (J C,F ) 3 Hz), 81.4 (J C,F ) 18 Hz), 87.2 (J C,F ) 181 Hz),
108.7, 123.9, 130.1, 141.1, 141.8; IR (KBr) ν (cm-1) 3440, 2933,
Starting from (1′R,2R,SS)-14 (700 mg, 2.48 mmol), the diol
(2R,3R,SS)-15 (560 mg, 75% yield) was isolated. Some of the
starting compound 14 (130 mg, 20%) was recovered unreacted.
2-{[(4-Meth ylp h en yl)su lfin yl]m eth yl}-3-flu or o-h ep t-6-
1493; MS (DIS EI, 70 eV) m/z (%) 299 [(M + H)+] (1), 298 [M+•
]
(1), 236 (18). Anal. Calcd for C15H19FO3S (298): C, 60.38; H,
6.42; F, 16.10. Found: C, 60.35; H, 6.44; F, 16.09.
Deoxygen a tion Rea ction . The general procedure used for
preparing trifluoro-derivatives 7 was applied on 16 (400 mg,
1.34 mmol). FC purification (diisopropyl ether/n-hexane 1:1)
allowed the isolation of pure 17 (358 mg, 1.27 mmol) (95%).
2-{[(4-Met h ylp h en yl)su lfen yl]m et h yl}-5-m et h yl-6,8-
en -1,2-d iol (2R,3R,SS)-15: [R]20 -164.80 (c 0.53, CHCl3); mp
D
1
79-80 °C (diisopropyl ether/n-hexane 1:1); H NMR (CDCl3)
δ 1.70, 1.85, 2.18, and 2.31 (m, 4H), 2.42 (br s, 3H), 2.91 (dd,
J ) 13.8 and 1.0 Hz, 1H), 3.16 (dd, J ) 13.8 and 1.2 Hz, 1H),
3.36 (br signal, 2H), 3.67 (dd, J ) 13.0 and 1.2 Hz, 1H), 3.74
(dd, J ) 13.0 and 1.5 Hz, 1H), 4.66 (ddd, J ) 48.5, 9.5, and
3.2 Hz, 1H), 5.02 and 5.07 (m, 2H), 5.79 (m, 1H), 7.36 and
7.56 (m, 4H); 19F NMR (CDCl3) δ -194.20 (br ddd, J ) 48.5,
38.8, and 18.0 Hz); IR (KBr) ν (cm-1) 3415, 2927, 1641, 1494;
MS (DIS EI, 70 eV) m/z (%) 301 [(M + H)+] (75), 283 (18), 269
(14). Anal. Calcd for C15H21FO3S: C, 59.98; H, 7.05; F, 6.32.
Found: C, 60.01; H, 7.06; F, 6.30.
d ioxa bicyclo[3.2.1]octa n e. (1R,2R,5R)-17: [R]20 -14.75 (c
D
0.66, CHCl3); mp 35-37 °C (diisopropyl ether/n-hexane 1:1);
1H NMR (CDCl3) δ 1.46 (s, 3H), 1.7-2.2 (m, 4H), 2.31 (br s, 3
H), 3.23 (dd, J ) 13.7 and 1.8 Hz, 1H), 3.34 (dd, J ) 13.7 and
1.2 Hz, 1H), 3.72 (br d, J ) 7.9 Hz, 1H), 4.17 (dd, J ) 7.9 and
1.8 Hz, 1H), 4.80 (dddd, J ) 49.6, 9.6, 6.8 and 1.3 Hz, 1H),
7.10 and 7.33 (m, 4H). 19F NMR (CDCl3) δ -187.63 (br dd, J
) 49.6 and 17.0 Hz); 13C NMR (CDCl3) δ 20.9, 23.2 (J C,F ) 3.5
Hz), 24.1 (J C,F ) 19.5 Hz), 35.5 (J C,F ) 7.5 Hz), 37.3, 69.0, 82.0
(J C,F ) 22.5 Hz), 88.0 (J C,F ) 183 Hz), 108.0, 129.6, 130.2, 132.8,
136.3; IR (KBr) ν (cm-1) 2935, 1494, 1440, 1390; MS (DIS EI,
70 eV) m/z (%) 282 [M+•] (55), 207 (6), 193 (5). Anal. Calcd for
Starting from (1′S,2R,SS)-14 (702 mg), the diol (2S,3S,SS)-
15 (575 mg, 77% yield) was isolated. Some of the starting
compound 14 (100 mg, 15%) was recovered unreacted.
(2R,3S,SS)-15: [R]20D -152.43 (c 0.57, CHCl3); mp 57-60 °C
(diisopropyl ether/n-hexane 1:1); 1H NMR (CDCl3) δ 1.75, 1.85,
2.17, and 2.30 (m, 4H), 2.42 (br s, 3H), 2.91 (br d, J ) 14.0 Hz,
1H), 3.14 (dd, J ) 14.0 and 1.2 Hz, 1H), 3.70 (br d, J ) 12.5
Hz, 1H), 3.74 (br signal, 2H), 3.88 (br d, J ) 12.5 Hz, 1H),
4.43 (ddd, J ) 48.0, 9.2, and 3.5 Hz, 1H), 5.01 and 5.06 (m,
2H), 5.79 (m, 1H), 7.36 and 7.57 (m, 4H). 19F NMR (CDCl3) δ
C
15H19FO2S (282): C, 63.81; H, 6.79; F, 6.73. Found: C, 63.80;
H, 6.82; F, 6.70.
Starting from (1R,2S,5R,SS)-16, the compound (1R,2S,5R)-
17 was obtained (350 mg, 1.23 mmol) in 92% yield.
(1R,2S,5R)-17: [R]20D -24.10 (c 0.50, CHCl3); mp 54-55 °C
1
(diisopropyl ether/n-hexane 1:1); H NMR (CDCl3) δ 1.45 (s,
-196.20 (br ddd, J ) 48.0, 36.0, and 21.0 Hz); IR (KBr) ν (cm-1
3396, 2926, 1639, 1495; MS (DIS EI, 70 eV) m/z (%) 301 [(M +
H)+] (20), 283 (19), 269 (16), 213 (5). Anal. Calcd for C15H21
)
3H), 1.61, 1.87, 1.89 and 2.04 (m, 4H), 2.32 (br s, 3 H), 3.13
(br d, J ) 13.4 Hz, 1H), 3.47 (dd, J ) 8.4 and 7.0 Hz, 1H),
3.48 (dd, J ) 13.4 and 1.0 Hz, 1H), 3.70 (d, J ) 8.4 Hz, 1H),
4.69 (ddd, J ) 48.4, 3.0 and 2.4 Hz, 1H), 7.11 and 7.31 (m,
4H); 19F NMR (CDCl3) δ -193.16 (dddd, J ) 48.4, 35.8, 27.2
and 6.8 Hz); 13C NMR (CDCl3) δ 21.0, 23.5 (J C,F ) 22.5 Hz),
-
FO3S: C, 59.98; H, 7.05; F, 6.32. Found: C, 60.00; H, 7.02; F,
6.31.
Wa ck er Oxid a tion . CuCl2 (333 mg, 2.49 mmol) and PdCl2
(249 mg, 1.41 mmol, 59% in weight) were added to 1,2-
dimethoxyethane (DME 2 mL), and the mixture was stirred
for 1 h at room temperature while an air stream was bubbled
into the slurry. A solution of sulfinyl diol 15 (500 mg, 1.67
mmol) in DME (2 mL) was added slowly to the vigorously
stirred mixture. The stirring was continued overnight, then
the reaction mixture was diluted with water and extracted
with ether (3 × 2 mL). The aqueous layer was acidified with
dilute HCl (0.5 N, 1.0 mL) to pH 2, left 2 h at room
temperature, and extracted with diethyl ether (3 × 5 mL). The
combined organics were washed with water, dried (Na2SO4),
and concentrated in vacuo. FC purification allowed the isola-
tion of the corresponding diastereomerically pure compound
16.
24.1, 31.1, 36.6 (J C,F ) 3.5 Hz), 70.4 (J C,F ) 4 Hz), 83.4 (J C,F
)
18 Hz), 85.1 (J C,F ) 181.5 Hz), 108.6, 129.8, 130.7, 131.6, 137.0;
IR (KBr) ν (cm-1) 2940, 2891, 1494, 1447; MS (DIS EI, 70 eV)
m/z (%) 282 [M+•] (23), 211 (4), 207 (5). Anal. Calcd for C15H19
-
FO2S: C, 63.81; H, 6.79; F, 6.73. Found: C, 63.83; H, 6.78; F,
6.75.
Red u ctive Desu lfen yla tion Rea ction . The general pro-
cedure used for preparing trifluoro-frontalines 8 was applied
on (1R,2R,5R)-17 (358 mg, 1.27 mmol). After distillation (oven
temperature 115 °C), fluorofrontalin (1R,2R,5R)-18 (176 mg,
1.1 mmol) was isolated in 88% yield as a clear oil.
1,5-Dim et h yl-2-flu or o-6,8-d ioxa b icyclo[3.2.1]oct a n e
(1R,2R,5R)-18: [R]20 -31.85 (c 2.7, CDCl3); bp ca. 105 °C; 1H
D
NMR (CDCl3) δ 1.41 and 1.45 (s, 6H), 1.6-2.2 (m, 4H), 3.46
(dd, J ) 7.5 and 1.1 Hz, 1H), 4.17 (dd, J ) 7.5 and 1.5 Hz,
1H), 4.43 (dddd, J ) 49.2, 9.2, 7.0, and 1.5 Hz, 1H); 19F NMR
(CDCl3) δ -186.83 (br dd, J ) 49.2 and 16.5 Hz); 13C NMR
(CDCl3) δ 19.0, 23.5 (J C,F ) 3.5 Hz), 24.4 (J C,F ) 20 Hz), 35.9
(J C,F ) 7.5 Hz), 70.7 (J C,F ) 2 Hz), 80.3 (J C,F ) 22.5 Hz), 90.8
(J C,F ) 182.5 Hz), 107.4 (J C,F ) 2 Hz); IR (film) ν (cm-1) 2940,
2889, 1719, 1458; MS (GC EI) m/z (%) 160 [M+•] (28), 130 (25),
Starting from (2R,3R,SS)-15, (1R,2R,5R,SS)-16 was obtained
(400 mg, 1.34 mmol) in 80% yield (FC with chloroform/ethyl
acetate, 7:3).
(1R,2R,5R,SS)-16: [R]20D -163.33 (c 0.32, CHCl3); mp 104-
106 °C (diisopropyl ether/n-hexane 1:1); 1H NMR (CDCl3) δ
1.53 (s, 3H), 1.7-2.2 (m, 4H), 2.42 (br s, 3 H), 3.02 (dd, J )
14.4 and 1.0 Hz, 1H), 3.26 (dd, J ) 14.4 and 2.1 Hz, 1H), 4.10
(br d, J ) 8.1 Hz, 1H), 4.21 (dd, J ) 8.1 and 1.8 Hz, 1H), 4.65
(dddd, J ) 49.5, 9.7, 6.6, and 1.5 Hz, 1H), 7.34 and 7.57 (m,
4H); 19F NMR (CDCl3) δ -187.64 (br dd, J ) 49.5 and 16.0
118 (70), 114 (45); GC/MS, tr, m/z (%) 7.16 min, 160 (99) [M+•
(1R,2R,5R)-18].
,
Hz); 13C NMR (CDCl3) δ 21.3, 23.1 (J C,F ) 4 Hz), 24.0 (J C,F
)
From (1R,2S,5R)-17 (350 mg, 1.23 mmol), keeping the oven
temperature at 115 °C, (1R,2S,5R)-20 (180 mg, 1.13 mmol) was
isolated in 90% yield as a clear oil.
20 Hz), 35.6 (J C,F ) 7.5 Hz), 61.5, 68.3 (J C,F ) 2 Hz), 80.5 (J C,F
) 22.5 Hz), 89.6 (J C,F ) 184 Hz), 108.8, 124.0, 130.1, 141.5,
141.9; IR (KBr) ν (cm-1) 3436, 2962, 1635, 1494; MS (DIS EI,
70 eV) m/z (%) 299 [(M + H)+] (1), 298 [M+•] (1), 236 (2), 159
(5). Anal. Calcd for C15H19FO3S: C, 60.38; H, 6.42; F, 16.10.
Found: C, 60.41; H, 6.40; F, 16.07.
(1R,2S,5R)-20: [R]20 -39.48 (c 1.5, CDCl3); bp ca. 105 °C;
D
1H NMR (CDCl3) δ 1.41 (d, J ) 0.7, 3H), 1.48 (s, 3H), 1.5-2.2
(m, 4H), 3.50 (dd, J ) 7.7 and 7.0 Hz, 1H), 3.78 (br d, J ) 7.0
Hz, 1H), 4.30 (ddd, J ) 48.2, 3.0, and 1.8 Hz, 1H); 19F NMR
Starting from (2R,3S,SS)-15, (1R,2S,5R,SS)-16 was obtained
(450 mg, 1.51 mmol) in 90% yield (FC with chloroform/ethyl
(CDCl3) δ -191.30 (dddd, J ) 48.2, 40.8, 20.5 and 7.6 Hz); 13
C
NMR (CDCl3) δ 18.3 (J C,F ) 4 Hz), 23.9 (J C,F ) 22.5 Hz), 24.3,
30.9, 72.0 (J C,F ) 4 Hz), 80.3 (J C,F ) 18.5 Hz), 88.3 (J C,F ) 181.5
Hz), 108.4; IR (CDCl3 solution) ν (cm-1) 2940, 2887, 1645, 1603;
MS (DIS EI, 70 eV) m/z (%) 160 [M+•] (5), 130 (5), 118 (18), 98
(19); GC/MS, tr, m/z (%): 7.18 min, 160 (95) [M+‚, (1R,2S,5R)-
20].
acetate, 7:3): [R]20 -168.56 (c 0.50, CHCl3); mp 98-9 °C
D
1
(diisopropyl ether/n-hexane 1:1); H NMR (CDCl3) δ 1.54 (s,
3H), 1.68, 1.91, 1.98, and 2.16 (m, 4H), 2.42 (br s, 3 H), 3.13
(br d, J ) 14.4 Hz, 1H), 3.26 (br dd, J ) 14.4 Hz, 1H), 3.94 (d,
J ) 8.4 Hz, 1H), 4.29 (dd, J ) 8.4 and 7.0 Hz, 1H), 4.48 (ddd,