T. Müller, M. Göhl, I. Lusebrink, K. Dettner, K. Seifert
FULL PAPER
combined organic extracts were passed through a plug of silica/
MgSO4. Evaporation of the solvent furnished the crude silyl ether
26 (5.743 g) which was sufficiently pure for the next step. An ana-
lytical sample of 26 was purified by column chromatography (silica
gel; n-hexane/CH2Cl2, 98:2; Rf = 0.3). [α]2D3 = +19.4 (c = 1.0,
MTBE). H NMR (300 MHz, CDCl3, 25 °C): δ = 5.76 (mc, 1 H,
2Ј-H), 5.24 (d, J = 9.9 Hz, 1 H, 3-H), 5.07–4.93 (m, 2 H, 3Ј-H),
4.03 (d, J = 1.0 Hz, 2 H, 1-H), 2.79 (mc, 2 H, 1Ј-H), 2.31 (mc, 1 H,
a catalytic amount of NaBr (6 mg, 0.06 mmol). This solution was
stirred in an oil bath at a temperature of 60 °C for about 2 h until
TLC indicated complete consumption of the mesylate (showed the
same Rf value as that for alcohol 27). The reaction mixture was
partitioned between water (80 mL) and MTBE (80 mL). The aque-
ous layer was extracted with MTBE (2ϫ80 mL). The combined
organic extracts were washed with brine and passed through a plug
of silica/MgSO4. Evaporation of the solvent furnished the crude
1
4-H), 1.36–1.19 (mc, 2 H, 5-H), 0.94 (d, J = 6.7 Hz, 3 H, 4-CH3), azide 28 (1.173 g) which was sufficiently pure for the next step. An
0.91 [s, 9 H, C(CH3)3], 0.84 (t, J = 7.4 Hz, 3 H, 6-H), 0.06 [s, 6 H,
analytical sample of 28 was purified by column chromatography
Si(CH3)2] ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ = 136.5 (C-
(silica gel; n-hexane/EtOAc, 95:5). [α]2D3 = +16.7 (c = 1.0, MTBE).
2Ј), 134.6 (C-2), 132.4 (C-3), 115.0 (C-3Ј), 66.5 (C-1), 33.5 (C-4), 1H NMR (300 MHz, CDCl3, 25 °C): δ = 5.18 (d, J = 10.0 Hz, 1
32.4 (C-1Ј), 30.3 (C-5), 26.0 [C(CH3)3], 20.8 (CH3-4), 18.4
[C(CH ) ], 12.0 (C-6), –5.2 [Si(CH ) ] ppm. FTIR (ATR): ν = 2959
H, 3Ј-H), 4.04 (d, J = 1.2 Hz, 2 H, 1Ј-H), 3.26 (t, J = 6.9 Hz, 2 H,
3ЈЈ-H), 2.27 (mc, 1 H, 4Ј-H), 2.12 (mc, 2 H, 1ЈЈ-H), 1.69 (mc, 2 H,
˜
3 3
3 2
(m), 2929 (m), 2856 (m), 1637 (w), 1462 (w), 1361 (w), 1252 (m), 2ЈЈ-H), 1.41–1.14 (m, 2 H, 5Ј-H), 0.93 (d, J = 6.6 Hz, 3 H, 4Ј-CH3)
1068 (m), 834 (vs), 773 (s) cm–1. GC–MS (EI, 70 eV): m/z (%) =
227 (4) [M – C3H5]+, 211 [M – tBu]+, 193 (8), 169 (4), 141 (29),
135 (12), 127 (5), 115 (6), 75 (100), 73 (30). HRMS (ESI): calcd.
for C16H32OSiNa [M + Na]+ 291.2115; found 291.2116.
0.90 [s, 9 H, C(CH3)3], 0.84 (t, J = 7.4 Hz, 3 H, 6Ј-H), 0.06 [s, 6 H,
Si(CH3)2] ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ = 135.6 (C-
2Ј), 133.0 (C-3Ј), 67.2 (C-1Ј), 51.4 (C-3ЈЈ), 33.5 (C-4Ј), 30.3 (C-
5Ј), 27.9 (C-2ЈЈ), 25.9 [C(CH3)3], 25.2 (C-1ЈЈ), 20.9 (CH3-4Ј), 18.4
[C(CH ) ], 11.9 (C-6Ј), –5.3 [Si(CH ) ] ppm. FTIR (ATR): ν = 2956
˜
3 3
3 2
(S,E)-4-[(tert-Butyldimethylsilyloxy)methyl]-6-methyl-oct-4-en-1-ol
(27): The crude silyl ether 26 (5.743 g, 21.4 mmol) was dissolved in
THF (20 mL), and 9-BBN-H (0.5 m in THF, 50.0 mL, 25 mmol)
was added at 0 °C over a period of 30 min by using a syringe pump.
The solution was allowed to reach room temp. overnight. To the
reaction mixture was added an aqueous solution of NaOH (3 m,
53 mL, 159 mmol) followed by the careful addition of H2O2 (30%,
18.1 mL) as the mixture was cooled with ice. After 3 h of stirring,
the reaction mixture was partitioned between water (200 mL) and
MTBE (200 mL). The aqueous layer was extracted with MTBE
(2ϫ100 mL). The combined organic extracts were passed through
a plug of silica/MgSO4. Evaporation of the solvent furnished the
crude alcohol 27 (9.07 g) which was purified by column chromatog-
raphy (silica gel; n-hexane/MTBE, 3:1; Rf = 0.4) to yield 27 as a
colorless oil (4.992 g, 17.42 mmol, 79% over three steps). Note: A
short flash column (6 cm diameter, 13 cm filling level) was used,
and the product was found in the fractions 5–10 (50 mL fraction
(w), 2929 (w), 2857 (w), 2093 (m), 1462 (w), 1253 (m), 1068 (m),
834 (s), 774 (s) cm–1. HRMS (ESI): calcd. for C16H33N3OSiNa [M
+ Na]+ 334.2285; found 334.2290.
(S,E)-2-(3-Azidopropyl)-4-methylhex-2-en-1-ol (6): The crude com-
pound 28 (1.173 g) obtained above was dissolved in a 1:1 mixture
of MeCN (15 mL) and DMF (15 mL), and hydrofluoric acid (40%,
2.5 mL) was added by using a syringe. This reaction mixture was
stirred for 2.5 h and quenched carefully with NaHCO3. Under vig-
orous stirring, MTBE (100 mL) and water (70 mL) were added,
and the layers were separated. The aqueous layer was extracted
with MTBE (2ϫ100 mL), and the combined organic layers were
washed with brine. The combined organic extracts were passed
through a plug of silica/MgSO4, and the solvent was removed un-
der reduced pressure. The residue was purified by column
chromatography (silica gel; n-hexane/MTBE, 3:1; Rf = 0.4) to yield
6 as a colorless oil (628 mg, 3.18 mmol, 77% over two steps).
[α]2D3 = +24.4 (c = 1, CHCl3). H NMR (300 MHz, CDCl3, 25 °C):
1
1
size). [α]2D3 = +18.7 (c = 1.0, MTBE). H NMR (300 MHz, CDCl3,
δ = 5.17 (d, J = 10.0 Hz, 1 H, 3-H), 3.97 (s, 2 H, 1-H), 3.24 (t, J
= 6.8 Hz, 2 H, 3Ј-H), 2.24 (m, 1 H, 4-H), 2.13 (m, 2 H, 1Ј-H), 1.65
(mc, 2 H, 2Ј-H), 1.38–1.25 (m, 1 H, 5-Ha), 1.25–1.13 (m, 1 H, 5-
Hb), 0.90 (d, J = 6.7 Hz, 3 H, 4-CH3), 0.80 (t, J = 7.4 Hz, 3 H, 6-
H) ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ = 136.0 (C-2), 134.4
(C-3), 66.8 (C-1), 51.1 (C-3Ј), 33.5 (C-4), 30.1 (C-5), 27.7 (C-2Ј),
25 °C): δ = 5.16 (d, J = 10.1 Hz, 1 H, 5-H), 4.06 (d, J = 1.5 Hz, 2
H, SiOCH2), 3.63 (t, J = 6.4 Hz, 2 H, 1-H), 2.29 (mc, 1 H, 6-H),
2.13, (mc, 2 H, 3-H), 1.80 (br., OH), 1.67 (mc, 2 H, 2-H), 1.40–1.13
(m, 2 H, 7-H), 0.92 (d, J = 6.6 Hz, 3 H, 6-CH3), 0.90 [s, 9 H,
C(CH3 )3 ], 0.83 (t, J = 7.4 Hz, 3 H, 8-H), 0.06 [s, 6 H,
Si(CH3)2] ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ = 136.3 (C-
4), 132.7 (C-5), 67.6 (SiOCH2), 62.8 (C-1), 33.5 (C-6), 31.8 (C-2),
30.3 (C-7), 25.9 [C(CH3)3], 24.4 (C-3), 20.8 (CH3-6), 11.9 (C-8),
25.1 (C-1Ј), 20.7 (CH -4), 11.8 (C-6) ppm. FTIR (ATR): ν = 3333
˜
3
(br.), 2958 (m), 2926 (w), 2872 (w), 2092 (vs), 1455 (m), 1370 (w),
1346 (w), 1255 (m), 1015 (m), 875 (w) cm–1. MS (CI): m/z (%) =
215 (40) [M + NH4]+, 198 (5) [M + H]+, 170 (28), 152 (100).
C10H19N3O (197.28): calcd. C 60.88, H 9.71, N 21.30; found C
60.89, H 9.71, N 21.29.
–5.3 [Si(CH ) ] ppm. FTIR (ATR): ν = 3347 (br.), 2956 (w), 2928
˜
3 2
(w), 2857 (w), 1461 (w), 1361 (w), 1253 (m), 1066 (m), 833 (vs), 773
(s) cm–1. GC–MS (EI, 70 eV): m/z (%) = 229 (29) [M – tBu]+, 199
(4), 185 (5), 173 (5), 159 (6), 145 (20), 137 (12), 119 (10), 109 (9),
97 (12), 95 (67), 81 (46), 75 (100), 73 (37). HRMS (ESI): calcd. for
C16H32O2SiNa [M + Na]+ 309.2220; found 309.2221.
(S,R,E,Z)-2-(3-Azidopropyl)-4-methylhex-2-en-1-ol
(6)
from
(S,R,E,Z)-18: To a solution of (S,R,E,Z)-18 (258 mg, 1.10 mmol)
in DMSO (3 mL) was added NaN3 (78 mg, 1.20 mmol), and the
reaction mixture was stirred at room temp. for about 3 h until TLC
showed a complete consumption of the starting material. The reac-
tion mixture was partitioned between water (20 mL) and MTBE
(40 mL). The aqueous layer was extracted with MTBE (2ϫ30 mL).
The combined organic extracts were washed with brine and passed
through a plug of silica/MgSO4, and the solvent was removed un-
der reduced pressure. The residue was purified in an identical way
as described above leaving the azide (S,R,E,Z)-6 (206 mg,
1.04 mmol, 95%).
[(S,E)-2-(3-Azidopropyl)-4-methylhex-2-enyloxy]-tert-butyldimethyl-
silane (28): Alcohol 27 (1.180 g, 4.12 mmol) was dissoloved in
CH2Cl2 (20 mL) and NEt3 (0.85 mL, 6.1 mmol) together with a
catalytic amount of DMAP (10 mg, 0.08 mmol). To this solution
was added dropwise mesyl chloride (0.35 mL, 4.5 mmol) at 0 °C.
After stirring for 1 h, most of the solvent was evaporated, and the
residue was partitioned between water (80 mL) and MTBE
(80 mL). The aqueous layer was extracted with MTBE (2ϫ80 mL).
The combined organic extracts were passed through a plug of silica/
MgSO4, and the solvent was removed under reduced pressure, leav-
ing the crude mesylate which was taken up directly in DMSO
(3 mL). To this solution was added NaN3 (325 mg, 5.00 mmol) and
{(2S,3S)-2-(3-Azidopropyl)-3-[(S)-sec-butyl]oxiran-2-yl}methanol
(5): Ti(OiPr)4 (300 μL, 1.01 mmol) was added to a suspension of
2328
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Eur. J. Org. Chem. 2012, 2323–2330