3.44 and 3.51 (2 × 1H, 2 × d, J 14.0, 10-H2), 3.85 (1H, dd, J 7.7,
5.2, 2-H); δC (75 MHz) 19.9 and 20.8 (C-8 and C-9), 23.2
(COCH3), 26.4, 32.8 and 38.4 (C-3, C-5 and C-6), 44.7 (C-4),
47.8 and 48.4 (C-1 and C-7), 52.8 (C-10), 65.2 (C-2) and
168.6 (COCH3); m/z (CI) 258.1159 (MHϩ, 100%. C12H20NO3S
requires 258.1164), 214 (28), 135 (93), 109 (24) and 83 (36). The
most polar fraction gave recovered auxiliary 39 (25.2 mg) as a
white solid.
minor diastereomer), 2.92 (1H, dd, J 17.0, 3.0, 2Ј-HH of major
diastereomer), 2.94 (1H, dd, J 17.0, 3.0, 2Ј-HH of minor
diastereomer), 3.12 (1H, br s, OH), 3.44 and 3.52 (2 × 1H,
2 × d, J 13.9, 10-H2), 3.88 (1H, dd, J 7.7, 5.1, 2-H), 4.27 (1H, m,
3Ј-H); δC (75 MHz) 19.8 and 20.8 (C-8 and C-9), 22.3 (C-4Ј),
26.4, 32.8 and 38.4 (C-3, C-5 and C-6), 43.7 (C-2Ј), 44.6 (C-4),
47.8 and 48.5 (C-1 and C-7), 52.9 (C-10), 64.2 (C-3Ј), 65.1 (C-2),
171.4 (C-1Ј); m/z (CI) 302.1422 (MHϩ, 29%. C14H24NO4S
requires 302.1426), 284 (37), 258 (25), 216 (100), 135 (63).
The above reaction was repeated using (1S,2R)-N-([1-13C]-
acetyl)bornane-10,2-sultam 41 (2.50 g, 9.69 mmol) giving
the [1Ј-13C]alcohols 43 (2.76 g, 94%) as a 3:1 mixture of
diastereomers by 1H-NMR spectroscopy.
The above reaction was repeated using sodium [1-13C]acetate
(2.498 g, 30.1 mmol) and (1S)-bornane-10,2-sultam 39 (7.127
g, 33.1 mmol). Purification by column chromatography eluting
with 0–50% ethyl acetate–petrol (40–60) gave three main frac-
tions. The least polar fraction gave 42 (0.32 g, 3.2% based on
39) as a white solid. Data as previously given. The middle frac-
tion gave the required (1S,2R)-N-([1-13C]acetyl)bornane-10,2-
sultam 41 (4.95 g, 64% based on sodium [1-13C]acetate) as
a white solid; δH (300 MHz) 0.97 and 1.16 (2 × 3H, 2 × s, 8-H3
and 9-H3), 1.38 (2H, m, 5-HH and 6-HH), 1.90 (3H, m, 4-H,
5-HH and 6-HH), 2.12 (2H, m, 3-H2), 2.41 (3H, d, J 6.5,
13COCH3), 3.43 and 3.51 (each 1H, each d, J 13.7, 10-H2), 3.85
(1H, dd, J 7.5 and 5.1, 2-H); δC (75 MHz) 19.9 and 20.8 (C-8
and C-9), 23.2 (d, J 51.5, 13COCH3), 26.4 and 32.8 (C-5 and
C-6), 38.4 (C-3), 44.6 (C-4), 47.7 and 48.3 (C-1 and C-7), 52.8
(C-10), 65.2 (C-2) and 168.6 (13CO enriched); m/z 258 (Mϩ, 9%),
243 (3), 215 (8), 151 (53), 134 (86) and 84 (100). The most polar
fraction gave recovered 39 (2.19 g) as a white solid.
The above reaction was repeated using (1S,2R)-N-([1,2-
13C2]acetyl)bornane-10,2-sultam 41 (3.0 g, 11.6 mmol) giving
the [1Ј,2Ј-13C2]alcohols 43 (3.29 g, 94%) as a 3:1 mixture of
diastereomers by 1H-NMR spectroscopy.
(1S,2R)-N-[(E)-Crotonyl]bornane-10,2-sultam 45
Pyridine (1 mL) and acetic anhydride (0.5 mL) were added
to (1S,2R)-N-[(3ЈRS)-3Ј-hydroxybutanoyl]bornane-10,2-sultam
43 (100 mg, 0.33 mmol) in dichloromethane (2 mL) at rt. The
reaction mixture was left standing at rt overnight, before
quenching with saturated aqueous sodium hydrogen carbonate
(20 mL). The layers were separated and the aqueous layer was
extracted with dichloromethane (3 × 20 mL). The organic phase
was washed with hydrochloric acid (2 M, 30 mL), saturated
aqueous brine (30 mL), dried (MgSO4) and the solvents
removed in vacuo. The crude product (0.21 g) was dissolved in
dichloromethane (4 mL), DBU (0.27 g, 1.61 mmol, 1.2 eq.) was
added and the reaction mixture was left standing overnight.
The reaction mixture was acidified with hydrochloric acid (2 M,
10 mL) and extracted with dichloromethane (3 × 20 mL). The
combined organic extracts were washed with saturated aqueous
brine (20 mL), dried (MgSO4) and the solvents removed in
vacuo. Purification by column chromatography eluting with
10–20% ethyl acetate–petrol (40–60) gave the title compound 45
(77 mg, 81%) as a white solid. Spectroscopic data as previously
reported.45
The above reaction was repeated using (1S,2R)-N-[(3ЈRS)-3Ј-
hydroxy[1-13C]butanoyl]bornane-10,2-sultam 43 (5.8 g, 16.6
mmol). Purification by column chromatography eluting with
10–20% ethyl acetate–petrol (40–60) gave (1S,2R)-N-[(E)-[1-
13C]crotonyl]bornane-10,2-sultam 45 (4.64 g, 85%) as a white
solid; δH (300 MHz) 0.98 and 1.18 (2 × 3H, 2 × s, 8-H3 and
9-H3), 1.40 (2H, m, 5-HH and 6-HH), 1.89 (3H, m, 4-H, 5-HH
and 6-HH), 2.13 (2H, m, 3-H2), 1.94 (3H, ddd, J 7.0, 1.7,
1.0, 4Ј-H3), 3.45 and 3.52 (2 × 1H, 2 × d, J 13.8, 10-H2), 3.93
(1H, m, 2-H), 6.59 (1H, ddq, J 15.0, 6.1, 1.7, 2Ј-H), 7.11 (1H,
dquintet, J 15.0, 7.0, 3Ј-H); δC (75 MHz) 18.3 (d, J 7.4, C-4Ј),
19.9 and 20.8 (C-8 and C-9), 26.5 and 32.8 (C-5 and C-6), 38.5
(C-3), 44.6 (C-4), 47.7 and 48.4 (C-1 and C-7), 53.1 (C-10), 65.1
(C-2), 122.2 (d, J 66.4, C-2Ј), 146.1 (C-3Ј), 164.0 (13C-1Ј);
m/z 284 (Mϩ, 17%), 269 (3), 220 (15), 205 (32), 108 (18) and
70 (100).
The above reaction was repeated using sodium [1,2-13C2]-
acetate (2.5048 g, 29.8 mmol) and (1S)-bornane-10,2-sultam 39
(7.081 g, 32.7 mmol). Purification by column chromatography
eluting with 0–50% ethyl acetate–petrol (40–60) gave 42 (2.32 g,
24% based on 39) followed by the required (1S,2R)-N-([1,2-13C2]-
acetyl)bornane-10,2-sultam 41 (5.81 g, 75% based on sodium
[1,2-13C2]acetate) as a white solid; δH (300 MHz) 0.97 and 1.16
(2 × 3H, 2 × s, 8-H3 and 9-H3), 1.38 (2H, m, 5-HH and 6-HH),
1.90 (3H, m, 4-H, 5-HH and 6-HH), 2.12 (2H, m, 3-H2), 2.40
(3H, dd, J 130.1 and 6.6, 13CO13CH3), 3.43 and 3.51 (each
1H, each d, J 13.8, 10-H2), 3.85 (1H, dd, J 7.6 and 5.4, 2-H);
δC (75 MHz) 19.9 and 20.8 (C-8 and C-9), 23.2 (d, J 51.5,
13CO13CH3), 26.4 and 32.8 (C-5 and C-6), 38.4 (C-3), 44.6
(C-4), 47.7 (C-1 or C-7), 48.3 (d, J 2.5, C-1 or C-7), 52.7 (C-10),
65.1 (C-2) and 168.6 (d, J 51.5, 13CO); m/z 259 (Mϩ, 9%), 244
(3), 215 (7), 134 (100) and 108 (76). The most polar fraction
gave recovered 39 (0.1 g) as a white solid.
(1S,2R)-N-[(3ЈRS)-3Ј-Hydroxybutanoyl]bornane-10,2-sultam
43
Titanium tetrachloride (1 M solution in dichloromethane, 7.0
mL, 7.0 mmol) was added slowly to (1S,2R)-N-acetylbornane-
10,2-sultam 41 (0.9 g, 3.5 mmol) in dry dichloromethane (5 mL)
at Ϫ78 ЊC in an oven dried flask under nitrogen. After 10 min-
utes, diisopropylethylamine (1.2 mL, 7.0 mmol) was added
dropwise and the reaction mixture was stirred for 0.5 h at
Ϫ78 ЊC. Acetaldehyde (~2.0 mL, ~35 mmol) was added and the
reaction mixture was stirred at Ϫ78 ЊC for 6 h, before allowing
to warm to rt overnight. Saturated aqueous ammonium chlor-
ide (40 mL) was added and the layers were separated. The
aqueous layer was extracted with dichloromethane (3 × 50 mL).
The combined organic extracts were washed with distilled water
(20 mL), dried (MgSO4) and the solvents removed in vacuo.
Purification by column chromatography eluting with 0–40%
ethyl acetate–petrol (40–60) gave the alcohols 43 (0.878 g, 83%)
The above reaction was repeated using (1S,2R)-N-[(3ЈRS)-
3Ј-hydroxy[1,2-13C2]butanoyl]bornane-10,2-sultam 43 (6.36 g,
21.0 mmol). Purification by column chromatography eluting
with 10–20% ethyl acetate–petrol (40–60) gave (1S,2R)-N-[(E)-
[1,2-13C2]crotonyl]bornane-10,2-sultam 45 (5.17 g, 86%) as a
white solid; δC (300 MHz) 0.98 and 1.18 (2 × 3H, 2 × s, 8-H3
and 9-H3), 1.41 (2H, m, 5-HH and 6-HH), 1.88 (3H, m, 4-H,
5-HH and 6-HH), 1.94 (3H, tdd, J 7.0, 1.7, 1.0, 4Ј-H3), 2.12
(2H, m, 3-H2), 3.45 and 3.52 (2 × 1H, 2 × d, J 13.8, 10-H2), 3.93
(1H, m, 2-H), 6.59 (1H, dddq, J 161.2, 15.0, 6.1, 1.7, 2Ј-H), 7.11
(1H, m, 3Ј-H); δC (75 MHz) 18.3 (d, J 8.7, C-4Ј), 19.9 and 20.8
(C-8 and C-9), 26.5 and 32.8 (C-5 and C-6), 38.5 (C-3), 44.7
(C-4), 47.7 (C-1 or C-7), 48.4 (d, J 2.5, C-1 or C-7), 53.1 (C-10),
65.1 (C-2), 122.3 (d, J 65.8, 13C-2Ј), 146.1 (d, J 71.3, C-3Ј), 164.0
1
as a 3:1 mixture of diastereomers by H-NMR spectroscopy;
mp 151–154 ЊC (from MeOH) (Found: C, 55.91; H, 7.55; N,
4.55; S, 10.32. C14H23NO4S requires C, 55.81; H, 7.64; N, 4.65;
S, 10.63%); νmax (CHCl3)/cmϪ1 3544 (OH) and 1682 (C᎐O);
᎐
δH (300 MHz) 0.98 and 1.15 (2 × 3H, 2 × s, 8-H3 and 9-H3), 1.25
(3H, d, J 6.4, 4Ј-H3), 1.40 (2H, m), 1.91 (3H, m), 2.13 (2H, m,
3-H2, 4-H, 5-H2 and 6-H2), 2.79 (1H, dd, J 17.0, 9.0, 2Ј-HH
of major diastereomer), 2.79 (1H, dd, J 17.0 and 9.0, 2Ј-HH of
J. Chem. Soc., Perkin Trans. 1, 2000, 3406–3416
3415