L
R. Sayini, P. Srihari
Paper
Synthesis
13C NMR (125 MHz, CDCl3): δ = 170.6, 146.7, 145.1, 140.4, 129.6,
128.5, 115.7, 93.9, 79.4, 55.6, 38.3.
MS (ESI): m/z = 361 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C11H15INaO4: 360.9913; found:
1H NMR (500 MHz, CDCl3): δ (major isomer) = 7.40–7.32 (m, 4 H),
7.31–7.27 (m, 1 H), 6.22–6.13 (m, 1 H), 5.73–5.63 (m, 2 H), 5.62–5.54
(m, 1 H), 4.84 (d, J = 2.2 Hz, 1 H), 4.62 (d, J = 2.7 Hz, 1 H), 4.46–4.34 (m,
1 H), 4.13–4.01 (m, 2 H), 3.85–3.74 (m, 1 H), 2.48 (q, J = 3.2, 2.1 Hz, 1
H), 2.24–2.16 (m, 1 H), 2.14–1.95 (m, 2 H), 1.88–1.80 (m, 1 H), 1.50–
1.34 (m, 4 H), 1.43 (s, 3 H), 1.41 (s, 3 H), 1.19 (d, J = 2.3 Hz, 3 H); δ
(minor isomer) = 7.39–7.32 (m, 4 H), 7.31–7.27 (m, 1 H), 6.51–6.43
(m, 1 H), 6.06–5.94 (m, 2 H), 5.48–5.39 (m, 1 H), 4.87 (d, J = 2.2 Hz, 1
H), 4.59 (d, J = 2.8 Hz, 1 H), 4.45–4.34 (m, 1 H), 4.15–4.02 (m, 2 H),
3.82–3.73 (m, 1 H), 2.48 (q, J = 3.2, 2.1 Hz, 1 H), 2.24–2.16 (m, 1 H),
2.14–1.95 (m, 2 H), 1.88–1.80 (m, 1 H), 1.50–1.34 (m, 4 H), 1.43 (s, 3
H), 1.41 (s, 3 H), 1.19 (d, J = 2.3 Hz, 3 H).
13C NMR (125 MHz, CDCl3): δ (major isomer) = 137.5, 135.1, 132.9,
131.3, 129.8, 128.3, 127.9, 126.2, 100.7, 80.0, 74.8, 70.8, 68.7, 68.0,
67.7, 67.5, 38.7, 33.4, 32.5, 27.6, 25.4, 24.8, 23.5; δ (minor isomer)
= 137.5, 135.1, 132.6, 130.6, 129.8, 128.1, 127.7, 126.2, 100.6, 80.0,
74.9, 70.7, 68.7, 68.0, 67.7, 67.5, 38.8, 33.3, 32.5, 27.6, 25.3, 24.8, 23.5.
360.9912.
[((1R,5E,7E)-8-{(4R,6R)-6-[(1S)-1-(Benzyloxy)prop-2-yn-1-yl]-2,2-
dimethyl-1,3-dioxan-4-yl}-1-methylocta-5,7-dien-1-yl)oxy](tert-
butyl)dimethylsilane (32)
A solution of endiyne 26 (0.02 g 0.03 mmol) in MeOH (5 mL) was
stirred in a 10 mL round-bottomed flask at r.t. under argon. To this
solution was added solid K2CO3 (0.009 g 0.06 mmol) to form a hetero-
geneous mixture that was vigorously stirred at r.t. until the reaction
was completed. The mixture was diluted with EtOAc and washed
with ice-cold H2O. The aqueous layer was extracted with EtOAc (2 ×
10 mL), and the combined organic fractions were washed with brine
then dried (Na2SO4). The residue was purified by column chromatog-
raphy [silica gel, hexane–EtOAc (9:1)] to give a colorless liquid; yield:
0.017 g (97%); [α]D25 +33.2 (c 1.8, CHCl3); Rf = 0.6 (hexane–EtOAc, 9:1).
MS (ESI): m/z = 421 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C25H34NaO4: 421.2355; found:
421.2365.
IR (neat): 2929, 2860, 1374, 1225, 1088, 1024, 836, 770, 661 cm–1
.
1H NMR (500 MHz, CDCl3): δ (major isomer) = 7.39–7.32 (m, 4 H),
7.31–7.27 (m, 1 H), 6.22–6.13 (m, 1 H), 5.73–5.62 (m, 2 H), 5.60–5.53
(m, 1 H), 4.84 (d, J = 2.44 Hz, 1 H), 4.62 (d, J = 3.2 Hz, 1 H), 4.45–4.34
(m, 1 H), 4.15–4.02 (m, 2 H), 3.82–3.73 (m, 1 H), 2.48 (t, J = 2.44 Hz, 1
H), 2.21–2.13 (m, 1 H), 2.10–1.94 (m, 2 H), 1.88–1.80 (m, 1 H), 1.50–
1.33 (m, 4 H), 1.42 (s, 3 H), 1.41 (s, 3 H), 1.12 (d, J = 3.6 Hz, 3 H), 0.88
(s, 9 H), 0.04 (s, 6 H); δ (minor isomer) = 7.39–7.32 (m, 4 H), 7.31–
7.27 (m, 1 H), 6.52–6.43 (m, 1 H), 6.05–5.92 (m, 2 H), 5.47–5.40 (m, 1
H), 4.87 (d, J = 2.44 Hz, 1 H), 4.59 (d, J = 3.2 Hz, 1 H), 4.45–4.34 (m, 1
H), 4.15–4.02 (m, 2 H), 3.82–3.73 (m, 1 H), 2.48 (t, J = 2.44 Hz, 1 H),
2.21–2.13 (m, 1 H), 2.10–1.94 (m, 2 H), 1.88–1.80 (m, 1 H), 1.50–1.33
(m, 4 H), 1.42 (s, 3 H), 1.41 (s, 3 H), 1.10 (d, J = 3.6 Hz, 3 H), 0.88 (s, 9
H), 0.04 (s, 6 H).
Methyl (2Z,4E,7S,8E)-9-Iodo-7-(methoxymethoxy)nona-2,4,8-trie-
noate (35)
The crude acid 5 (0.003 g, 0.008 mmol) was esterified with MeI (0.8
ml, 0.013 mmol) then added to a suspension of Cs2CO3 (3.18 mg,
0.009 mmol) in DMF (4 mL). After stirring at 0–5 °C for 4 h, the mix-
ture was poured into cold H2O and extracted with EtOAc (2 × 5 mL).
The extracts were dried (Na2SO4), filtered, and concentrated under re-
duced pressure. The residue was purified by column chromatography
[silica gel, hexane–EtOAc (9:1)] to give a colorless oil; yield: 0.025 mg
(83%); [α]D25 –0.16 (c 0.5, CHCl3); Rf = 0.7 (hexane–EtOAc, 6:4).
IR (KBr): 2991, 2928, 1615, 1459, 1380, 1216, 1160, 1078, 1019, 845,
784 cm–1
.
13C NMR (125 MHz, CDCl3): δ (major isomer) = 137.5, 135.6, 133.1,
131.5, 129.6, 128.3, 127.9, 127.7, 100.7, 80.1, 74.8, 70.8, 70.7, 68.7,
68.4, 67.6, 39.2, 33.4, 31.9, 27.8, 25.9, 25.4, 24.8, 23.9, 18.1, –4.4, –4.7;
δ (minor isomer) = 137.5, 135.6, 132.6, 130.4, 129.6, 128.3, 127.9,
126.4, 100.6, 80.0, 74.8, 70.8, 70.7, 68.7, 68.4, 67.5, 39.1, 33.8, 32.6,
27.8, 25.7, 25.3, 24.8, 23.8, 18.1, –4.4, –4.7.
1H NMR (400 MHz, CDCl3): δ = 7.43–7.36 (m, 1 H), 6.58–6.51 (m, 1 H),
6.08–6.01 (m, 1 H), 5.82 (dd, J = 2.3, 0.9 Hz, 1 H), 5.59 (d, J = 11.4 Hz, 1
H), 5.33 (dd, J = 2.3, 0.6 Hz, 1 H), 4.61 (d, J = 6.6 Hz, 1 H), 4.48 (d, J = 6.6
Hz, 1 H), 3.72 (s, 3 H), 3.33 (s, 3 H), 2.54–2.47 (m, 1 H), 2.38–2.28 (m, 1
H).
13C NMR (100 MHz, CDCl3): δ = 166.7, 145.2, 144.6, 139.2, 129.5,
116.3, 93.9, 79.3, 60.4, 55.6, 51.2, 38.2.
MS (ESI): m/z = 535 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C31H48NaO4Si: 535.3220; found:
MS (ESI): m/z = 375 [M + Na]+.
535.3243.
HRMS (ESI): m/z [M + Na]+ calcd for C12H17INaO4: 375.0069; found:
375.0074.
(2R,6E,8E)-9-{(4R,6R)-6-[(1S)-1-(benzyloxy)prop-2-yn-1-yl]-2,2-
dimethyl-1,3-dioxan-4-yl}nona-6,8-dien-2-ol (4)
Methyl (2Z,4E,7R,8E,12S)-12-(Benzyloxy)-12-{(4R,6R)-6-
A 1 M solution of TBAF in THF (0.1 mL, 0.117 mmol) was added at 0 °C
to a solution of the silyl ether 26 (0.02 g, 0.039 mmol) in anhyd THF
(10 mL), and the mixture was stirred for 1 h. Sat. aq NH4Cl (10 mL)
and EtOAc (30 mL) were added, and the phases were separated. The
aqueous layer was extracted with EtOAc (3 × 10) and the organic
phases were combined, washed sequentially with water and brine,
dried (Na2SO4), and concentrated. The residue was purified by flash
column chromatography [silica gel, hexane–EtOAc (8:2)] to give a col-
[(1E,3E,8R)-8-hydroxynona-1,3-dien-1-yl]-2,2-dimethyl-1,3-diox-
an-4-yl}-7-(methoxymethoxy)dodeca-2,4,8-trien-10-ynoate (37)
To a solution of vinyl iodide 35 (0.005 g, 0.014 mmol) in Et3N (5 mL,
0.036 mmol, 2.6 equiv) under argon were added PdCl2(PPh3)2 (2 mg,
0.0014 mmol, 0.2 equiv) and CuI (2 mg, 0.008 mmol, 0.6 equiv). The
mixture was stirred for 15 min, and then a solution of alkyne 4 (0.006
g, 0.017 mmol, 1.2 equiv) in THF (0.6 mL) was added dropwise over 30
min. The mixture was stirred for 10 h and then diluted with Et2O (150
mL). The resulting mixture was washed with sat. aq NH4Cl (2 × 3 mL).
The organic layer was dried (Na2SO4) and filtered. The filtrate was
concentrated in vacuo, and the crude residue was purified by column
chromatography [silica gel, EtOAc–PE (2:8)] to give a colorless oil;
yield: 5.46 mg (70%); [α]D25 +0.88 (c 0.3, CHCl3); Rf = 0.8 (hexane–EtOAc,
8:2).
25
orless oil; yield: 0.014 g (93%); [α]D + 35.23 (c 1.7, CHCl3); Rf = 0.7
(hexane–EtOAc, 8:2).
IR (neat): 3306, 2926, 2858, 1713, 1459, 1376, 1224, 1083, 991, 739,
699, 663 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–M