by flash chromatography (ethyl acetate–hexane, 1:4) followed
by crystallisation (diethyl ether) providing the title compound
(25–34 mg, 65–89%) as colourless crystals: mp 147–148 °C.
Specific rotation: []D −61.0 (c 1.0, CH2Cl2). Analysis (%): Calc.
for C19H29NO5S: C 59.5, H 7.63, N 3.65. Found: C 59.50, H 7.85,
N 3.57; IR (Nujol): max 2852, 2360, 1686, 1460, 1377, 1329, 1211,
1210, 1134, 838, 776, 735, 698 cm−1; 1H NMR (200 MHz, CDCl3):
0.06 (6H, s), 0.88 (9H, s), 0.93 (3H, s), 1.12 (3H, s), 1.19–1.40
(2H, m), 1.56–1.69 (4H, m), 1.79–1.96 (3H, m), 1.99–2.04 (2H, m),
2.07–2.30 (2H, m), 2.38–2.56 (1H, m), 2.61–2.75 (1H, m), 3.19–
3.30 (1H, m), 3.35–3.52 (4H, m), 3.70–3.88 (3H, m), 4.05–4.13
(1H, m), 4.48 (2H, s), 5.32–5.52 (2H, m), 7.13–7.33 (5H, m); 13C
NMR (50 MHz, CDCl3): −5.6, 18.0, 19.8, 20.7, 23.6, 25.8, 26.3,
26.8, 29.4, 32.8, 36.2, 38.3, 44.5, 47.5, 47.9, 50.2, 53.1, 62.0, 65.0,
69.7, 70.7, 72.7, 125.9, 127.3, 127.5, 127.6, 128.2, 130.5, 131.4,
138.5, 171.2. HRMS: Calc. C34H55NO6SSi: [M + Na]+ m/z 656.342.
Found: 656.339.
1
1162, 1136, 1069, 953, 770, 722, 653 cm−1; H NMR (300 MHz,
CDCl3): 0.96 (3H, s), 1.13 (3H, s), 1.17 (3H, d, J 6.1 Hz), 1.23–1.44
(2H, m), 1.50 (3H, s), 1.56 (1H, ddd, J 2.0, 3.8 and 13.3 Hz), 1.68
(1H, ddd, J 3.6, 10.9 and 13.3 Hz), 1.80–1.96 (3H, m), 2.03–2.12
(2H, m), 2.17 (1H, dd, J 4.8 and 13.6 Hz), 2.42 (1H, dd, J 9.1 and
13.6 Hz), 3.44 and 3.51 (2H, AB quartet, J 13.8 Hz), 3.55 (1H, dd,
J 4.8 and 9.1 Hz), 3.87 (1H, dd, J 5.4 and 7.2 Hz), 3.91–3.98 (1H,
m), 4.69 (1H, br s); 13C NMR (75 MHz, CDCl3): 19.8, 20.9, 21.7,
24.1, 26.3, 32.9, 37.3, 38.5, 39.8, 44.6, 47.5, 47.7, 48.5, 53.1, 65.2,
65.7, 77.9, 105.7, 172.3. HRMS: Calc. C19H29NO5S: [M + Na]+ m/z
406.166. Found: 406.165.
(2R)-N-[(1S,5S,6R)-1-{4-Benzyloxybut-1-yl}-2,8-dioxabicyclo-
[3.2.1]octanyl-6-carbonyl]bornane-10,2-sultam 15. Using the
general Wacker reaction procedure described in general remarks,
Pd(II)-catalysed cyclisation of aldol adduct 14 (0.1 mmol scale) for
8 h afforded, upon work-up, a yellow residue which was purified
by flash chromatography (ethyl acetate–hexane, 1:1) providing
the title compound (20 mg, 39%) as colourless oil: IR (neat): max
2945, 1949, 1872, 1715, 1690, 1268, 1210, 1130, 774, 690 cm−1; 1H
NMR (300 MHz, CDCl3): 0.98 (3H, s), 1.16 (3H, s), 1.25–1.42
(2H, m), 1.43–1.60 (6H, m), 1.69–1.90 (5H, m), 2.02–2.12 (2H, m),
2.24 (1H, dd, J 4.6 and 13.7 Hz), 2.38 (1H, dd, J 9.0 and 13.7 Hz),
3.42–3.55 (4H, m), 3.60 (1H, dd, J 4.6 and 9.0 Hz), 3.87–3.96 (3H,
m), 4.49 (2H, s), 4.72 (1H, br s), 7.27–7.33 (5H, m); 13C NMR
(75 MHz, CDCl3): 18.9, 19.5, 19.9, 25.4, 28.8, 28.9, 31.9, 36.5,
36.9, 37.6, 43.6, 45.7, 46.8, 47.5, 52.2, 58.6, 64.8, 69.3, 71.8, 77.2,
106.6, 126.4, 126.6, 127.3, 137.7, 171.4. HRMS: Calc. C28H39NO6S:
[M + Na]+ m/z 540.240. Found: 540.238.
(2R)-N-[(2R,3S,5S)-2-Allyl-5-(tert-butyldimethylsilyloxy)-
hexan-1-oyl]bornane-10,2-sultam 12. Using the general aldol
reaction procedure described in general remarks, aldol addition
of acyl sultam 3a (1 mmol) to aldehyde 4d with the reaction time
of 3 h afforded upon work-up crude product as a yellow residue.
Purification by flash chromatography (ethyl acetate–hexane)
followed by recrystallisation (diethyl ether–hexane) provided
adduct 12 (467 mg, 94%) as colourless crystals: mp 138–141 °C.
Specific rotation: []D −61.0 (c 1.0, CH2Cl2); IR (Nujol): max
3499, 2960, 1699, 1462, 1335, 1265, 1210, 1133, 1065, 990, 836,
1
778 cm−1; H NMR (300 MHz, CDCl3): 0.08 (3H, s), 0.09 (3H,
s), 0.85 (9H, s), 0.95 (3H, s), 1.15 (3H, s), 1.16 (3H, d, J 6.0 Hz),
1.21–1.42 (2H, m), 1.54 (1H, ddd, J 2.0, 4.6 and 14.3 Hz), 1.69
(1H, ddd, J 8.7, 9.6 and 14.3 Hz), 1.82–1.96 (3H, m), 1.99–2.09
(2H, m), 2.53–2.69 (2H, m), 3.17–3.24 (1H, m), 3.42 and 3.50 (2H,
AB quartet, J 13.8 Hz), 3.88 (1H, t, J 6.3 Hz), 4.00–4.11 (2H, m),
4.94–5.09 (2H, m), 5.58 (1H, ddt, J 6.2, 10.0 and 16.6 Hz); 13C
NMR (75 MHz, CDCl3): −4.8, −4.1, 17.9, 19.9, 20.8, 24.0, 25.0,
26.4, 32.9, 33.8, 38.4, 43.7, 44.6, 47.7, 48.0, 50.6, 53.3, 65.2, 69.6,
70.3, 117.3, 135.0, 174.2. HRMS: Calc. C25H45NO5SSi: [M + Na]+
m/z 522.269. Found: 522.268.
(1R,3S,5R,6S)-1,3-Dimethyl-6-hydroxymethyl-2,8-dioxa-
bicyclo[3.2.1]octane 16. A solution of LiAlH4 (4 mg, 0.1 mmol) in
diethyl ether (1 mL) was stirred under a nitrogen atmosphere and
cooled to 0 °C while a solution of 7 (82 mg, 0.21 mmol) in diethyl
ether (2 mL) was added dropwise. The reaction mixture was stirred
at this temperature for 45 min and water (20 L) was added. The
mixture was warmed to room temperature, filtered through a bed of
MgSO4 and the filtrate concentrated in vacuo. The resulting yellow
oil was purified by flash chromatography (ethyl acetate–dichloro-
methane, 1:4) to afford the title compound (32 mg, 87%) as a
colourless oil: 1H NMR (300 MHz, CDCl3): 1.18 (3H, d, J 6.1 Hz),
1.23–1.42 (2H, m), 1.46 (3H, s), 1.67–1.76 (1H, m), 2.02 (1H, br s),
2.21–2.34 (2H, m), 3.52 (2H, d, J 5.7 Hz), 3.91–4.08 (1H, m) and
4.35 (1H, br s); 13C NMR (75 MHz, CDCl3): 21.9, 24.6, 37.9, 38.0,
44.5, 65.3, 65.6, 77.4, 105.4. HRMS: Calc. C9H16O3: [M + Na]+ m/z
195.0997. Found: 195.0993.
(2R)-N-[(1S,3S,5S,6R)-1,3-Dimethyl-2,8-dioxabicyclo[3.2.1]-
octanyl-6-carbonyl]bornane-10,2-sultam 13. Using the general
Wacker reaction procedure described in general remarks, Pd(II)-
catalysed cyclisation of aldol adduct 12 (0.1 mmol scale) overnight
afforded, upon work-up, a yellow residue which was purified by
flash chromatography (ethyl acetate–hexane, 1:4) providing the
title compound (19 mg, 50%) as a white solid: IR (Nujol): max
2932, 2359, 1688, 1460, 1377, 1326, 1159, 1133, 953, 770, 722,
2,3-Bis(phenylmethyloxy)-5-[(1,1-dimethylethyl)dimethyl-
silyloxy]-D-xylose 18. tert-Butyldimethylsilyl chloride (7.25 g,
48 mmol) was added to a magnetically stirred solution of 2,3-
di-O-benzyl-D-xylose diethyl dithioacetal 17 (17.5 g, 40 mmol)
and imidazole (3.55 g, 52 mmol) in anhydrous DMF (50 mL)
maintained at rt under an atmosphere of nitrogen. After 12 h the
reaction mixture was poured into water (500 mL) and extracted
with CH2Cl2 (3 × 300 mL). The combined organic phases were
washed with water (400 mL) and brine (400 mL) before being
dried (MgSO4), filtered and concentrated under reduced pressure
to afford a light yellow oil. Flash chromatography (5–25% v/v
ethyl acetate–hexane elution) gave the title compound (20.9 g,
95%) as a yellow oil. Specific rotation: []D −5.1 (c 1.1, CHCl3);
IR (neat): max 3450, 3063, 2949, 1497, 1454, 1389, 1254, 1121,
842 cm−1; 1H NMR (300 MHz): 0.05 (3H, s), 0.06 (3H, s), 0.90
(9H, s), 1.22 (6H, m), 2.72 (4H, m), 3.51 (1H, d, J 9.8), 3.53 (1H,
d, J 9.8), 3.65 (1H, d, J 9.7), 3.77 (1H, ddd, J 8.5, 6.6 and 2.0 Hz),
4.04 (2H, m), 4.14 (1H, d, J 3.0 Hz), 4.62 (1H, d, J 11.1 Hz), 4.83
(1H, d, J 11.1 Hz), 4.87 (2H, AB system, J 11 Hz), 7.24–7.37
(10H, m); 13C NMR (75 MHz): −5.1 (2 × CH3, coincident),
14.6 (CH3), 14.7 (CH3), 25.4 (C), 26.1 (3 × CH3, coincident),
26.2 (2 × CH2, coincident), 53.6 (CH), 64.1 (CH2), 71.7 (CH),
75.5 (CH2), 75.7 (CH2), 79.7 (CH), 83.7 (CH), 127.7 (CH), 128.0
(2 × CH, coincident), 128.2 (2 × CH, coincident), 128.4 (2 × CH,
1
653 cm−1; H NMR (300 MHz, CDCl3): 0.95 (3H, s), 1.12 (3H,
s), 1.16 (3H, d, J 6.1 Hz), 1.22–1.42 (2H, m), 1.50 (3H, s), 1.57
(1H, ddd, J 2.0, 3.7 and 13.3 Hz), 1.69 (1H, ddd, J 3.6, 10.9 and
13.3 Hz), 1.83–1.95 (3H, m), 2.02–2.12 (2H, m), 2.16 (1H, dd, J 4.8
and 13.6 Hz), 2.40 (1H, dd, J 9.1 and 13.6 Hz), 3.45 and 3.50 (2H,
AB quartet, J 13.8 Hz), 3.54 (1H, dd, J 4.7 and 9.1 Hz), 3.81–3.89
(1H, m), 3.90–3.96 (1H, m), 4.69 (1H, br s); 13C NMR (75 MHz,
CDCl3): 19.8, 20.8, 21.5, 24.0, 26.4, 32.8, 37.4, 38.4, 40.4, 44.6,
47.4, 47.7, 48.5, 53.2, 65.0, 65.6, 78.1, 105.9, 172.3. HRMS: Calc.
C19H29NO5S: [M + Na]+ m/z 406.166. Found: 406.165.
(2R)-N-[(4Z)-{(1S)-3-(tert-Butyldimethylsilyloxy)-1-
hydroxyprop-1-yl)-8-benzyloxyocten-1-oyl]bornane-10,2-
sultam 14. Using the general aldol reaction procedure described in
general remarks, acyl sultam 3b (223 mg, 0.5 mmol) in dry dichloro-
methane (2 mL) was reacted with freshly prepared diethylboron
triflate (1 mmol) at −10 °C to give the corresponding diethylboron
enolate which was cooled to −78 °C.Aldehyde 4a (188 mg, 1 mmol)
was added and the reaction mixture stirred at this temperature for
5 h. The resulting yellow residue obtained upon work-up was
subjected to flash chromatography (ethyl acetate–hexane, 1:3)
to provide the title compound (225 mg, 71%) as a yellow oil: IR
(neat): max 3490, 2954, 1950, 1870, 1717, 1694, 1454, 1335, 1267,
2 2 2 6
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 2 2 2 0 – 2 2 2 8