Full Paper
2
4.8, 24.8, 20.1, 19.9, 17.9, 17.9, 15.1, 13.5, –4.1, –4.3, –4.4, –4.4 ppm.
3.84–3.79 (m, 0.22 H), 3.75–3.70 (m, 0.78 H), 2.48 (br. t, J = 7.5 Hz,
2 H), 2.40 (br. t, J = 7.5 Hz, 2 H), 2.30 (q, J = 7.0 Hz, 2 H), 2.13 (dd,
J = 2.1, 13.2 Hz, 1 H), 1.99 (dd, J = 9.6, 13.2 Hz, 1 H), 1.72 (br. s, 0.8
H), 1.71–1.66 (m, 1 H), 1.61 (br. s, 2.2 H), 1.59–1.51 (m, 2 H), 1.45
FTIR (film): ν˜ = 3069, 2956, 2930, 2857, 1728, 1596, 1498, 1380, 837,
–1
+
7
76 cm . MS (ESI): m/z = 569.6 [M + Na] . HRMS (ESI): calcd. for
+
C H N O SSi [M + H] 547.2769; found 547.2767.
27 43 4 4
(
ddd, J = 4.4, 9.5, 14.0 Hz, 1 H), 1.36–1.30 (m, 1 H), 1.22–1.17 (m, 1
Condensation of 36 with Aldehyde 37 To Give 38: NaHMDS
1.0 in THF; 0.13 mL, 0.13 mmol) was added to a stirred solution
of 36 (68 mg, 0.12 mmol) in dry THF (1 mL) at –75 °C under argon
balloon). Stirring was continued at the same temperature for 1 h,
then a solution of aldehyde 37 (18 mg, 0.14 mmol) in dry THF
1 mL) was added. After the addition was complete, the mixture
H), 1.12 (ddd, J = 3.2, 9.7, 13.3 Hz, 1 H), 0.90 (d, J = 6.6 Hz, 3 H)
(
M
ppm. 13C NMR [125 MHz, CDCl , with resolved signals for the minor
3
(
Z) isomer indicated with an asterisk when different from those for
the major (E) isomer]: δ = 142.77 (C-20), 142.67 (C-20)*, 142.60 (C-
)*, 142.59 (C-1), 138.90 (C-21)*, 138.87 (C-21), 138.74 (C-4), 132.82
(
1
(
(
(
C-8), 132.53 (C-8)*, 128.08 (C-7)*, 127.79 (C-7), 125.25 (C-18), 125.22
C-18)*, 124.63 (C-4), 124.62 (C-4)*, 111.01 (C-2), 111.00 (C-2)*,
was stirred at –75 °C for another 5 h. After this time, TLC showed
that the reaction was complete. Water (3 mL) was added. The mix-
ture was extracted with EtOAc (3 × 20 mL). The combined organic
layers were washed with saturated aq. Na SO and brine, and dried
1
4
2
2
1
10.91 (C-19), 67.10 (C-11)*, 66.03 (C-11), 48.85 (C-10), 44.63 (C-12)*,
4.51 (C-12), 40.92 (C-10)*, 37.43 (C-14)*, 37.39 (C-14), 29.43 (C-13)*,
9.20 (C-13), 28.50 (C-6)*, 28.41 (C-6), 27.37 (C-16)*, 27.34 (C-16),
5.12 (C-5)*, 24.99 (C-5), 24.84 (C-17), 23.76 (C-9)*, 19.29 (C-14),
9.19 (C-14)*, 16.17 (C-9) ppm. IR (film): ν˜ = 3440, 3133, 3104, 2928,
2
3
with anhydrous Na SO . Removal of the solvent by rotary evapora-
2
4
tion and column chromatography (petroleum ether/EtOAc, 50:1) on
silica gel gave 38 [(E)/(Z) = 3:1, 39 mg, 0.09 mmol, 71 %] as a colour-
–
1
2
2
1
2855, 1567, 1501, 1459, 1380, 874, 778 cm . MS (ESI): m/z = 331.4
[
found 353.2093.
less oil. [α]D = –21.2 (c = 1.0, CHCl ). H NMR (400 MHz, CDCl ): δ =
3
3
+
+
M + H] . HRMS (ESI): calcd. for C H O Na [M + Na] 353.2087;
21 30 3
7
.35–7.33 (m, 2 H), 7.21 (br. s, 2 H), 6.27 (br. s, 1.5 H), 6.26 (br. s, 0.5
H), 5.22 (br. t, J = 7.0 Hz, 0.25 H), 5.16 (br. t, J = 6.9 Hz, 0.75 H),
.90–3.78 (m, 1 H), 2.47–2.37 (m, 4 H), 2.29–2.17 (m, 3 H), 2.05 (dd,
J = 7.6, 13.1 Hz, 1 H), 1.69 (d, J = 1.1 Hz, 0.7 H), 1.63–1.60 (m, 1 H),
.58 (br. s, 2.3 H), 1.57–1.51 (m, 1 H), 1.38–1.24 (m, 2 H), 1.23–1.15
m, 1 H), 1.13–1.07 (m, 1 H), 0.89 (s, 2.4 H), 0.88 (s, 6.6 H), 0.84 (d,
3
Oxidation of ent-1 To Give ent-2: A mixture of ent-1 (11 mg,
.033 mmol), NaHCO (4.1 mg, 0.05 mmol), and Dess–Martin period-
0
3
1
(
inane (15 wt.-% in CH Cl ; 0.1 mL, 0.05 mmol) in dry CH Cl (2 mL)
2
2
2
2
was stirred at ambient temperature for 15 min. After this time, TLC
showed that the reaction was complete. The solvent was removed
by rotary evaporation. The residue was purified by column chroma-
tography (petroleum ether/EtOAc, 15:1) on silica gel to give ent-2
(
J = 6.5 Hz, 0.75 H), 0.83 (d, J = 6.6 Hz, 2.25 H), 0.06–0.04 (m, 6 H)
ppm. 13C NMR (100 MHz, CDCl ): δ = 142.6, 142.6, 138.8, 138.7,
3
1
6
2
–
1
32.9, 132.9, 126.6, 126.6, 125.3, 125.3, 124.9, 124.8, 111.0, 111.0,
8.9, 68.8, 48.9, 44.3, 44.2, 41.1, 37.4, 37.4, 28.6, 28.6, 28.4, 27.4, 25.9,
5.1, 24.9, 24.9, 24.3, 19.5, 19.4, 18.1, 18.1, 16.6, –4.0, –4.1, –4.5,
4.6 ppm. FTIR (film): ν˜ = 3137, 3107, 2950, 2929, 2856, 1563, 1501,
25
9 mg, 0.03 mmol, 82 %) as a colourless oil. [α] = +6.0 (c = 0.7,
D
[6]
22
1
CHCl ) {ref. [α] = –8.1 (c = 2.31, CHCl ) for natural 2}. H NMR
3
D
3
(500 MHz, CDCl ): δ = 7.34 (br. s, 2 H), 7.21 (br. s, 1 H), 7.20 (br. s, 1
3
–
1
+
462, 1379, 874, 774 cm . MS (ESI): m/z = 445.5 [M + H] . HRMS
H), 6.27 (br. s, 1 H), 6.26 (br. s, 1 H), 5.40 (br. t, J = 6.9 Hz, 0.25 H),
.28 (br. t, J = 6.7 Hz, 0.75 H), 3.07 (br. s, 0.5 H), 3.01 (br. s, 1.5 H),
Desilylation of 38 To Give ent-1: A solution of 38 (35 mg, 2.50–2.45 (m, 2 H), 2.41–2.37 (m, 2 H), 2.32 (dd, J = 5.7, 14.8 Hz, 2
+
(ESI): calcd. for C H NaO Si [M + Na] 467.2952; found 467.2956.
27 44 3
5
0
.08 mmol) and nBu NF (1.0
M
in THF; 0.6 mL, 0.6 mmol) was stirred
H), 2.21 (dd, J = 7.9, 16.4 Hz, 2 H), 2.05–1.97 (m, 1 H), 1.70 (br. s, 0.8
H), 1.59 (br. s, 2.2 H), 1.58–1.48 (m, 2 H), 1.33–1.26 (m, 1 H), 1.22–
1.14 (m, 1 H), 0.89 (d, J = 5.8 Hz, 0.75 H), 0.87 (d, J = 6.5 Hz, 2.25 H)
4
at ambient temperature for 12 h. The mixture was then diluted with
EtOAc (20 mL), and washed with water (3 × 2 mL) and brine, then
it was dried with anhydrous Na SO . Removal of the solvent by
ppm. 13C NMR [125 MHz, CDCl , with resolved signals for the minor
2
4
3
rotary evaporation and column chromatography (petroleum ether/ (Z) isomer indicated with an asterisk when different from those for
EtOAc, 50:1 to 10:1) on silica gel gave ent-1 [a 3:1 inseparable mix- the major (E) isomer]: δ = 209.40 (C-11), 208.38 (C-11)*, 142.71 (C-
ture of (E) and (Z) isomers, 17 mg, 0.05 mmol, 65 %] as a colourless
20)*, 142.68 (C-1), 142.66 (C-20), 138.89 (C-4)*, 138.88 (C-4), 138.76
oil, along with recovered 38 (8 mg, 0.018 mmol, 23 %). Data for ent-
(C-21), 129.74 (C-8), 129.24 (C-8)*, 128.96 (C-7), 128.11 (C-1)*, 125.04
2
5
[6]
20
1
: [α] = –8.4 (c = 1.0, CHCl ) {ref. [α] = +8.9 (c = 1.0, CHCl ) for (C-18), 125.02 (C-18)*, 124.60 (C-3), 124.54 (C-3)*, 110.96 (C-2),
D
3
D
3
1
natural 1}. H NMR (500 MHz, C D ): δ = 7.15 (br. s, 1 H), 7.13 (br. s, 110.95 (C-19), 110.93 (C-19)*, 54.48 (C-10), 49.40 (C-12)*, 49.00 (C-
6
6
1
H), 7.09 (br. s, 0.75 H), 7.08 (br. s, 0.25 H), 7.06 (br. s, 1 H), 6.11 (br.
12), 47.11 (C-10)*, 36.42 (C-15), 28.91 (C-6)*, 28.88 (C-13)*, 28.83 (C-
s, 0.75 H), 6.10 (br. s, 0.25 H), 6.09 (br. s, 0.25 H), 6.07 (br. s, 0.75 H),
13), 28.48 (C-6), 27.41 (C-16), 24.83 (C-17), 24.69 (C-5), 24.20 (C-9)*,
1
5
3
.26 (br. t, J = 7.0 Hz, 0.25 H), 5.17 (br. t, J = 6.9 Hz, 0.75 H), 3.75–
.69 (m, 1 H), 2.34–2.20 (m, 4 H), 2.11 (q, J = 7.2 Hz, 2 H), 2.03–1.95 (br. s, 1 H), 7.14–7.12 (m, 1 H), 7.07 (br. s, 2 H), 6.09 (br. s, 2 H), 5.28
19.79 (C-14), 16.48 (C-9) ppm. H NMR (500 MHz, C D ): δ = 7.15
6
6
(
1
(
m, 1.5 H), 1.90 (dd, J = 4.5, 13.3 Hz, 0.5 H), 1.87–1.82 (m, 0.75 H),
.81–1.75 (m, 0.25 H), 1.63 (br. s, 0.75 H), 1.58–1.46 (m, 3 H), 1.45
br. s, 2.25 H), 1.36–1.26 (m, 1 H), 1.21–1.14 (m, 1 H), 1.09–1.03 (m,
(br. t, J = 7.2 Hz, 0.25 H), 5.15 (dt, J = 1.1, 7.0 Hz, 0.75 H), 2.83 (br.
s, 0.5 H), 2.78 (br. s, 1.5 H), 2.33–2.29 (m, 2 H), 2.24–2.20 (m, 2 H),
2.16–2.09 (m, 2 H), 2.07–2.00 (m, 2 H), 1.96–1.90 (m, 1 H), 1.67 (br.
d, J = 1.2 Hz, 0.75 H), 1.54 (br. s, 2.25 H), 1.46–1.32 (m, 2 H), 1.23–
1.16 (m, 1 H), 1.06–0.98 (m, 1 H), 0.83 (d, J = 6.6 Hz, 2.25 H), 0.82
(d, J = 6.6 Hz, 0.75 H) ppm. 13C NMR [125 MHz, C D , with resolved
1
H), 0.93 (d, J = 6.6 Hz, 2.25 H), 0.89 (d, J = 6.6 Hz, 0.75 H) ppm.
C NMR [125 MHz, C D , with resolved signals for the minor (Z)
1
3
6
6
isomer indicated with an asterisk when different from those for the
6
6
major (E) isomer]: δ = 143.08 (C-20), 143.03 (C-20)*, 142.97 (C-1)*, signals for the minor (Z) isomer indicated with an asterisk when
1
8
42.96 (C-1), 139.33 (C-21)*, 139.32 (C-21), 139.21 (C-4), 133.19 (C- different from those for the major (E) isomer]: δ = 206.97 (C-11),
), 132.92 (C-8)*, 127.80 (C-7), 125.52 (C-18), 125.49 (C-18)*, 124.94 206.11 (C-11)*, 143.05 (C-20)*, 143.02 (C-20), 143.01 (C-1), 139.34 (C-
(C-4)*, 124.92, 111.31 (C-2), 111.28 (C-2)*, 111.19 (C-19), 67.19 (C- 4), 139.32 (C-4)*, 139.23 (C-21), 130.36 (C-8), 129.78 (C-8)*, 128.83
1
1
6
2
1)*, 66.30 (C-11), 49.50 (C-10), 45.01 (C-12), 41.48 (C-10)*, 37.88 (C- (C-7), 125.34 (C-18), 125.30 (C-18)*, 124.88 (C-3)*, 124.86 (C-3),
4), 37.85 (C-14)*, 29.46 (C-13), 29.44 (C-13)*, 28.99 (C-6)*, 28.73 (C- 111.25 (C-2), 111.24 (C-19), 111.22 (C-19)*, 54.47 (C-10), 49.39 (C-
), 27.87 (C-16), 27.86 (C-16)*, 25.45 (C-5)*, 25.31 (C-5), 25.11 (C-17), 12)*, 48.97 (C-12), 47.09 (C-10)*, 36.68 (C-15), 36.66 (C-15)*, 29.31
1
4.01 (C-9)*, 19.55 (C-14), 19.44 (C-14)*, 16.22 (C-9) ppm. H NMR
(C-6)*, 28.92 (C-13)*, 28.89 (C-13), 28.77 (C-6), 27.81 (C-16), 25.16 (C-
5)*, 25.13 (C-17), 25.12 (C-17)*, 24.99 (C-5), 24.40 (C-9)*, 19.99 (C-
14), 19.96 (C-14)*, 16.56 (C-9) ppm. IR (film): ν˜ = 3134, 2926, 2855,
(500 MHz, CDCl ): δ = 7.34 (br. s, 2 H), 7.21 (br. s, 2 H), 6.26 (br. s, 2
3
H), 5.37 (br. t, J = 6.9 Hz, 0.25 H), 5.25 (br. t, J = 6.8 Hz, 0.75 H),
955
Eur. J. Org. Chem. 2016, 946–957
www.eurjoc.org
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim