SYNTHESIS
Papers
476
68.8, 70.6, 70.8, 72.2, 74.0, 80.3, 80.4, 87.6, 95.1, 96.6, 169.2, 169.5,
170.3, 170.6.
C15H24O8 (332.4): calcd. C, 54.21; H, 7.28; found C, 58.43; H, 7.29.
protons were recorded in a ratio of 16:2:4:67:1:10. The signal of 29
had decreased to a value of 10%, whereas the most intensive signal
(67%) corresponded to that of 28.
When the alcohol 27 was oxidized by the Swern procedure the crude
product consisted in a mixture of the aldehyde 29 and 28 in a 1:3 ratio.
(1R,5R,6R,8R,10S)-5-Acetoxymethyl-10-methoxy-9,9-dimethyl-
8-(prop-2-enyl)-2,4,7-trioxabicyclo[4.4.0]decane (40):
(1R,5R,6R,8R,10S)-5-Acetoxymethyl-8-(2,3-dihydroxypropyl)-
10-methoxy-9,9-dimethyl-2,4,7-trioxabicyclo[4.4.0]decane (41a
and 42a):
Molecular sieves 4 Å were added to a solution of the anomers of 39
(1.09 g, 3.28 mmol) in MeCN (45 mL). The mixture was stirred for
30 min at 0°C and allyltrimethylsilane (3.1 mL, 20 mmol) was added.
After stirring for 15 min, BF3•OEt2 (0.45 mL, 4.9 mmol) was added
dropwise. The mixture was stirred for 2 h at 0°C and poured into a
well agitated mixture of tert-butyl methyl ether (300 mL) and satd aq
NaHCO3 solution (150 mL). The phases were separated and the aque-
ous phase was extracted with tert-butyl methyl ether (3 × 150 mL).
The combined organic phases were washed with brine (25 mL), dried
(Na2SO4), and concentrated. Flash chromatography of the residue
with petroleum ether/tert-butyl methyl ether (3:2) furnished 0.870 g
A solution of 40 (0.304 g, 0.97 mmol) in H2O (4 mL) and tert-butyl
alcohol (4 mL) was added to a mixture of K2OsO4•2H2O (5 mg,
0.01 mmol), dihydroquinine-9-phenanthryl ether (24 mg, 0.05 mmol),
K3Fe(CN)6 (0.981g, 2.98 mmol) and K2CO3 (0.450 g, 3.26 mmol) in
tert-butyl alcohol (6 mL) and H2O (6 mL) at 0°C. After stirring for
3 h at 0°C Na2SO3 (1.103 g, 5.8 mmol) were added. The phases were
separated and the aqueous phase was extracted with EtOAc (5 ×
20 mL). The combined organic phases were washed with brine (5 mL),
dried (Na2SO4) and concentrated. Flash chromatography with EtOAc
furnished 0.31 g (92%) of a 2:1 mixture of the diols 41a and 42a.
1H NMR (300 MHz, CDCl3), major diastereomer: δ = 0.80 (s, 3 H),
0.89 (s, 3 H), 1.15–1.58 (m, 3 H), 2.04 (s, 3 H), 3.39–3.53 (m, 7 H),
3.78–3.94 (m, 3 H), 4.00–4.17 (m, 3 H), 4.50 (d, J = 11.0 Hz, 1 H),
4.79 (d, J = 6.6 Hz, 1 H), 4.93 (d, J = 6.6 Hz, 1 H). The following sig-
nals of the minor diastereomer could be recorded: δ = 0.77 (s, 3 H),
2.05 (s, 3 H), 4.64 (d, J = 11.8 Hz, 1 H).
(84%) of 40 as a colorless oil; [α]20 +117 (c = 1.180, CHCl3).
D
1H NMR (500 MHz, CDCl3): δ = 0.85 (s, 3 H), 0.98 (s, 3 H), 2.00–
2.08 (m, 1 H), overlayed with 2.08 (s, 3 H), 2.16 (dd, J = 14.4, 6.8 Hz,
1 H), 3.25 (dd, J = 10.2, 1.9 Hz, 1 H), 3.40 (d, J = 10.4 Hz, 1 H), 3.53
(s, 3 H), 3.97 (dd, J = 10.7, 6.9 Hz, 1 H), 4.03 (dd, J = 12.1, 6.8 Hz, 1
H), 4.15 (2 dd, J = 10.3, 6.9 Hz, 2 H), 4.45 (dd, J = 12.1, 1.8 Hz, 1 H),
4.84 (d, J = 6.6 Hz, 1 H), 4.97 (d, J = 6.6 Hz, 1 H), 5.01–5.05 (m, 2
H), 5.75–5.85 (m, 1 H).
13C NMR (75 MHz, CDCl3), mixture of diastereomers: δ = 13.0, 13.1,
20.7, 20.8, 22.7, 22.9, 32.1, 32.2, 41.2, 41.6, 61.6, 63.8, 66.4, 66.5,
67.0, 67.2, 67.4, 68.0, 71.1, 71.4, 73.0, 73.3, 74.1, 78.3, 78.7, 79.1,
86.6, 86.7, 171.1, 171.7.
13C NMR (75 MHz, CDCl3): δ = 13.3, 20.8, 23.1, 33.4, 41.6, 61.7,
63.7, 67.3, 71.2, 73.5, 78.6, 79.2, 86.9, 116.6, 135.8, 170.7.
C16H26O6 (314.4): calcd C, 61.13; H, 8.34; found C, 60.91; H, 8.58.
C16H28O8 (348.4): calcd C, 55.16; H, 8.10; found C, 55.14; H, 7.98.
(1R,5R,6R,8R,10S)-5-Hydroxymethyl-10-methoxy-9,9-dimethyl-
8-(prop-2-enyl)-2,4,7-trioxabicyclo[4.4.0]decane (27):
(1R,5R,6R,8R,10S)-5-Acetoxymethyl-8-(3-tert-butyldimethylsil-
oxy-2-hydroxypropyl)-10-methoxy-9,9-dimethyl-2,4,7-trioxabi-
cyclo[4.4.0]decane (41b/42b):
Solid K2CO3 (1.01 g, 7.3 mmol) was added to a solution of 40
(535 mg, 1.2 mmol) in MeOH (20 mL) and H2O (10 mL). After stir-
ring for 30 min the solution was concentrated and the residue was par-
titioned between H2O (10 mL) and tert-butyl methyl ether (25 mL).
The phases were separated and the aqueous phase was extracted with
tert-butyl methyl ether (3 × 25 mL). The combined organic phases
were washed with brine (5 mL), dried (MgSO4) and concentrated.
Flash chromatography of the residue with tert-butyl methyl ether fur-
nished 357 mg (99%) of the alcohol 27 as a slightly yellowish oil;
[α]D20 +97.4 (c = 0.975, CHCl3).
Imidazole (0.11 g, 1.73 mmol) and later tert-butylchlorodimethylsi-
lane (0.26g, 1.73 mmol) were added to a solution of the diols 41a/42a
(0.547 g, 1.57 mmol) in DMF (50 mL) at 0°C. The mixture was al-
lowed to reach r.t. with stirring over 19 h and was poured into H2O
(25 mL). The mixture was extracted with tert-butyl methyl ether
(4 × 25 mL). The combined organic phases were washed with brine
(5 mL), dried (Na2SO4) and concentrated. Flash chromatography with
petroleum ether/tert-butyl methyl ether (1:1, containing 1% of EtN3)
furnished 0.306 g (42%) of 41b, 0.130 g (18%) of 42b, and 0.141 g
(19%) of a mixed fraction, which could be combined for separation
with the next batch processed.
1H NMR (300 MHz, CDCl3): δ = 0.83 (s, 3 H), 0.96 (s, 3 H), 1.93–
2.04 (m, 1 H), 2.10–2.16 (m, 1 H), 2.36 (br s, 1 H), 3.22 (dd, J = 10.1,
2.2 Hz, 1 H), 3.51–3.52 (m, 1 H), overlayed with 3.52 (s, 3 H), 3.59–
3.65 (m, 1 H), 3.76–3.82 (m, 1 H), 3.95–3.98 (m, 2 H), 4.11 (dd, J =
10.4, 6.3 Hz, 1 H), 4.82 (d, J = 6.5 Hz, 1 H), 4.96–5.05 (m, 3 H), 5.67–
5.91 (m, 1 H).
41b: [α]D20 +72.64 (c = 3.013, CHCl3).
1H NMR (300 MHz, CDCl3): δ = 0.03 (s, 6 H), 0.86 (s, 12 H), 0.93 (s,
3 H), 1.40 (ddd, J = 14.6, 10.0, 7.9 Hz, 1 H), 1.77 (ddd, J = 14.6, 3.9,
2.0 Hz, 1 H), 2.07 (s, 3 H), 2.97 (br s, 1 H), 3.36–3.47 (m, 3 H), 3.49–
3.58 (m, 4 H), 3.70 (m, 1 H), 3.98 (dd, J = 10.5, 6.8 Hz, 1 H), 4.07–
4.23 (m, 3 H), 4.49 (dd, J = 11.7, 1.4 Hz, 1 H), 4.83 (d, J = 6.6 Hz, 1
H), 4.98 (d, J = 6.6 Hz, 1 H).
13C NMR (75 MHz, CDCl3): δ = 13.1, 23.0, 33.4, 41.5, 61.6, 63.0,
68.0, 73.0, 73.4, 78.4, 79.2, 86.8, 116.8, 135.7.
C14H24O5 (272.3): calcd C, 71.74; H, 8.88; found C, 61.71; H, 9.15.
13C NMR (75 MHz, CDCl3): δ = –5.4 (2C), 13.3, 18.2, 20.8, 23.1,
25.8 (3C), 32.4, 41.7, 61.6, 63.8, 66.5, 67.5, 71.2, 71.6, 73.2, 78.6,
79.0, 86.9, 170.7.
(1R,5S,6S,8R,10S)-5-Formyl-10-methoxy-9,9-dimethyl-8-(prop-
2-enyl)-2,4,7-trioxabicyclo[4.4.0]decane (29):
Compound 27 (274 mg, 1.0 mmol) was oxidized with Dess-Martin-
periodinane as described for the preparation of 28 to give 182 mg of
crude 29.
C22H42O8Si (462.7): calcd C, 57.11; H, 9.15; found C, 56.91; H, 8.98.
42b: [α]D20 +90.8 (c = 0.595, CHCl3).
1H NMR (300 MHz, C6D6): δ = 0.84 (s, 3 H), 1.01 (s, 3 H), 2.00–2.11
(m, 1 H), 2.34–2.44 (m, 1 H), 2.90 (d, J = 7.5 Hz, 1 H), 3.21 (s, 3 H),
3.27 (dd, J = 10.7, 2.6 Hz, 1 H), 3.37–3.40 (m, 1 H), 3.87–3.95 (m, 1
H), 4.08 (dd, J = 7.6, 5.1 Hz, 1 H), 4.58 (d, J = 6.6 Hz, 1 H), 4.64 (d,
J = 6.6 Hz, 1 H), 5.07–5.14 (m, 2 H), 5.93–6.06 (m, 1 H), 9.43 (d, J =
1.1 Hz, 1 H).
1H NMR (300 MHz, CDCl3): δ = 0.04 (s, 6 H), 0.83 (s, 3 H), 0.87 (s,
9 H), 0.95 (s, 3 H), 1.27–1.45 (m, 2 H), 2.09 (s, 3 H), 2.86 (d, J =
4.4 Hz, 1 H), 3.37–3.48 (m, 2 H), 3.53–3.61 (m, 5 H), 3.76–3.80 (m,
1 H), 3.95 (dd, J = 10.9, 7.0 Hz, 1 H), 4.04 (dd, J = 12.1, 6.7 Hz, 1 H),
4.12–4.23 (m, 2 H), 4.61 (dd, J = 12.1, 1.5 Hz, 1 H), 4.85 (d, J =
6.6 Hz, 1 H), 5.00 (d, J = 6.6 Hz, 1 H).
13C NMR (75 MHz, C6D6): δ = 24.6, 33.4 (2C), 39.0, 60.4, 64.0, 72.8,
78.1, 79.7, 80.9, 87.8, 116.0, 136.7, 197.8.
13C NMR (75 MHz, CDCl3): δ = -5.3 (2C), 13.2, 18.3, 20.9, 22.9, 25.9
(3C), 32.1, 41.4, 61.8, 64.0, 67.3, 67.7, 67.9, 71.5, 73.7, 74.1, 79.4,
86.9, 171.1.
Treatment of a benzene-d6 solution of 29 (57 mg) with DBU (5 mg)
1
led to changes in the H NMR spectrum. Six signals for aldehydic
C22H42O8Si (462.7): calcd C, 57.11; H, 9.15; found C, 57.37; H 8.98.