The Journal of Organic Chemistry
Article
EtOH (7 mL), NaBH4 (47.7 mg, 1.26 mmol, 0.75 equiv), 1 M HCl (5
mL), extraction with CH2Cl2 (3 × 15 mL), washing with H2O and
brine (15 mL each), and purification on SiO2 (hexanes/EtOAc 10:1)
gave 19b (286 mg, 1.44 mmol, 86%) as a yellowish oil in a
851 (w), 750 (w), 556 (w) cm−1; HRMS (ESI-TOF) m/z: [M + H]+
calcd for C6H9O3 129.0546; found 129.0545.
Dimethyl (E)-5-Hydroxy-6-[(R)-5-(trimethylsilyl)pent-4-yn-2-
yl]hept-2-enedioate (21). To a solution of 12 (2.24 g, 10.6 mmol,
1.0 equiv) in CH2Cl2 (53 mL) at −78 °C was added a 1 M solution of
NaHMDS−THF (12.7 mL, 2.32 g, 12.7 mmol, 1.2 equiv), and the
reaction mixture was stirred for 30 min. Then, TMSCl (1.61 mL, 1.38
g, 12.7 mmol, 1.2 equiv) was added and the reaction mixture was
stirred for a further 30 min at −78 °C. After addition of 11 (2.03 g,
15.8 mmol, 1.5 equiv) and a 1 M solution of TiCl4−CH2Cl2 (10.6
mL, 2.0 g, 10.6 mmol, 1.0 equiv), the reaction mixture was stirred at
−78 °C for 3 h. The reaction was quenched by addition of a satd.
solution of NH4Cl−H2O (3 mL), and the mixture was extracted with
CH2Cl2 (3 × 5 mL). The combined organic layers were washed with a
satd. solution of NH4Cl−H2O (2 × 5 mL) and H2O (2 × 5 mL) and
dried (MgSO4). All volatile materials were removed under reduced
pressure and the residue was purified by column chromatography on
SiO2 (hexanes/EtOAc 6:1) to give 21 (2.36 g, 6.93 mmol, 66%) as an
1
diastereomeric ratio (dr) of 31:29:22:19 (by H NMR, 1″-H). Rf =
1
0.17; H NMR (500 MHz, CDCl3) δ (ppm) = 4.20 (q, J = 8.0, 7.6
Hz, 2H, OCH2CH3), 4.09−4.17 (m, 1H, 1′-H), 3.95−4.04 (m, 1H,
1′-H*), 2.77 (dd, J = 12.0, 9.9 Hz, 1H, OH), 2.54−2.60 (m, 1H, 5-
H), 2.46−2.53 (m, 1H, 5-H*), 2.35−2.45 (m, 2H, 5-H*, 3-Ha),
2.03−2.34 (m, 4H, 4-H, 3-Ha*, 3-Hb, 3-Hb*), 1.96−2.02 (m, 1H, 1-
H), 1.18−1.24 (m, 3H, 2′-H), 1.28 (m, 3H, OCH2CH3), 1.15 (d, J =
6.4 Hz, 3H, 1″-H*), 1.09 (d, J = 6.9 Hz, 3H, 1″-H*), 1.03−1.06 (m,
3H, 1″-H*), 1.01 (d, J = 6.9 Hz, 3H, 1″-H); 13C{1H} NMR (126
MHz, CDCl3) δ (ppm) = 173.3, 173.5, 175.0, 175.1 (C-6), 81.7, 82.0,
82.6, 83.2 (C-2), 69.8, 70.0, 70.2, 70.5 (C-1), 66.0, 66.1, 66.6, 66.9
(C-1′), 60.5, 60.6, 60.7, 60.8 (OCH2CH3), 55.6, 56.2, 57.09, 57.14
(C-5), 31.3, 31.55, 31.63, 32.2 (C-4), 23.1, 23.6, 24.2, 24.9 (C-3),
20.7, 21.0, 22.1, 22.5 (C-2′), 17.0, 17.3, 17.5, 18.1 (C-1″), 14.4, 14.5
1
orange oil in a diastereomeric ratio (dr) of 57:20:17:5 (by H NMR,
(OCH2CH3); FT-IR (ATR): ν = 3447 (b), 3302 (m), 2973 (m),
̃
1′-H). Rf = 0.22 (hexanes/EtOAc 4:1); [α]2D0 = +20 (c 1.0, CHCl3).
1H NMR (500 MHz, CDCl3) δ (ppm) = 5.83 (dt, J = 15.2, 6.5 Hz,
1H, 8-H), 5.70 (dd, J = 15.6, 7.1 Hz, 1H, 9-H*), 5.53−5.63 (m, 1H,
9-H), 4.41−4.49 (m, 1H, 6-H*), 4.33−4.40 (m, 1H, 6-H), 3.65−3.69
(m, 6H, OCH3), 3.08 (dd, J = 7.1, 4.0 Hz, 2H, 7-H), 2.98 (s, 1H,
OH), 2.53−2.74 (m, 1H, 5-H*), 2.41−2.48 (m, 2H, 5-H, 3-H*),
2.26−2.41 (m, 1H, 3-H), 2.05−2.25 (m, 2H, 4-H, 3-H**), 1.15 (d, J
= 6.6 Hz, 3H, 1′-H), 1.07 (d, J = 6.3 Hz, 3H, 1′-H*), 1.02 (d, J = 6.8
Hz, 3H, 1′-H*), 0.99 (d, J = 6.9 Hz, 3H, 1′-H*), 0.13 (s, 9H,
Si(CH3)3); 13C{1H} NMR (126 MHz, CDCl3) δ (ppm) = 173.3,
174.9, 175.0 (COO), 171.84, 171.86, 171.88 (C-10), 133.5, 134.6,
134.8 (C-9), 123.7, 124.1, 125.3 (C-8), 104.3, 104.7, 105.8 (C-2),
86.4, 86.7, 87.1 (C-1), 70.1, 70.4, 71.3 (C-6), 54.5, 55.2, 55.9 (C-5),
51.6, 51.7, 51.8, 52.0 (OCH3), 37.6 (C-7), 31.6, 31.8, 32.3 (C-4),
24.5, 25.1, 25.4 (C-3), 17.4, 17.5, 18.1 (C-1′), 0.20, 0.23 Si(CH3)3;
2935 (m), 1711 (s), 1459 (m), 1377 (m), 1342 (w), 1299 (m), 1249
(m), 1176 (s), 1094 (m), 1023 (s), 958 (w), 908 (w), 780 (m), 633
(m), 648 (m), 471 (w) cm−1; MS (ESI-TOF) m/z: 221.12 [M +
Na]+, 199.13 [M + H]+, 125.09 [M − COOCH2CH3]; HRMS (ESI-
TOF) m/z: [M + Na]+ calcd for C11H18O3Na 221.1148; found
221.1154.
Methyl (R)-3-Methyl-6-(trimethylsilyl)hex-5-ynoate (12). In
analogy to ref 22, to a solution of 17b (1.48 g, 5.47 mmol, 1.0 equiv)
in DMF (11 mL) were added H2O (0.2 mL, 197 mg, 11.0 mmol, 2.0
equiv) and LiCl (464 mg, 11.0 mmol, 2.0 equiv), and the reaction
mixture was stirred at 140 °C for 8 h using an oil bath. After cooling
down to room temperature, brine (20 mL) was added, and the
mixture was extracted with CH2Cl2 (3 × 30 mL). The combined
organic layers were washed with H2O (2 × 20 mL) and dried
(MgSO4), and the solvent was removed under reduced pressure. The
residue was purified by column chromatography on SiO2 (hexanes/
EtOAc 30:1) to give 12 (936 mg, 4.41 mmol, 81%) as a yellowish oil.
FT-IR (ATR): ν = 3509 (br), 2956 (m), 2174 (m), 1731 (s), 1436
̃
(m), 1328 (m), 1249 (s), 1196 (m), 1163 (s), 1032 (m), 975 (m),
943 (w), 841 (vs), 760 (m), 699 (w), 648 (m), 571 (w), 458 (w)
cm−1; MS (ESI-TOF) m/z: 363.16 [M + Na]+, 309.15 [M −
OCH3]+, 291.14, 267.14 [M − (SiCH3)3]+, 219.10, 191.11, 159.08,
131.08; HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C17H28O5SiNa
363.1598; found 363.1590.
Rf = 0.61 (hexanes/EtOAc 10:1); [α]2D0 = −7 (c 1.0, CHCl3). H
1
NMR (500 MHz, CDCl3) δ (ppm) = 3.67 (s, 3H, OCH3), 2.41−2.53
(m, 1H, 4-H), 2.22−2.25 (m, 2H, 5-H), 2.16−2.22 (m, 2H, 3-H),
1.03 (d, J = 6.0 Hz, 3H, 1′-H), 0.14 (s, 9H, (Si(CH3)3); 13C{1H}
NMR (126 MHz, CDCl3) δ (ppm) = 173.2 (C-1′), 104.8 (C-2), 86.4
(C-1), 51.5 (OCH3), 40.1 (C-5), 29.6 (C-4), 26.9 (C-3), 19.4 (C-1′),
Dimethyl (2E,4E)-6-[(R)-5-(Trimethylsilyl)pent-4-yn-2-yl]-
hepta-2,4-dienedioate (22). In analogy to ref 36, to a solution of
21 (370 mg, 1.09 mmol, 1.0 equiv) in CH2Cl2 (5.4 mL) at 0 °C were
0.1 (Si(CH3)3); FT-IR (ATR): ν = 2959 (m), 2174 (m), 1737 (s),
̃
1458 (w), 1436 (m), 1369 (w), 1344 (w), 1311 (m), 1249 (m), 1213
(w), 1163 (m), 1082 (w), 1036 (m), 1010 (w), 941 (w), 837 (vs),
759 (s), 699 (w), 647 (m), 578 (w), 456 (w) cm−1; MS (ESI-TOF)
m/z: 235.11 [M + Na]+, 213.13 [M + H]+, 181.10; HRMS (ESI-
TOF) m/z: [M + Na]+ calcd for C11H20O2SiNa 235.1125; found
235.1119.
added MsCl (101 μL, 149 mg, 1.30 mmol, 1.2 equiv), Hunig base
̈
(0.4 mL, 309 mg, 2.39 mmol, 2.2 equiv), and DMAP (1.33 mg, 10.9
μmol, 0.01 equiv), and the reaction mixture was warmed to room
temperature and stirred for 20 h. The reaction was quenched by
addition of H2O (5 mL), and the reaction mixture was extracted with
CH2Cl2 (3 × 5 mL). The combined organic layers were filtered
through SiO2, and the phase was rinsed with CH2Cl2 (10 mL). The
filtrate was concentrated to give 22 (295 mg, 915 μmol, 84%) as a
Methyl (E)-5-Oxopent-2-enoate (11). To a solution of methyl
(E)-5-hydroxypent-2-enoate31,32 (1.75 g, 13.5 mmol, 1.0 equiv) in
CH2Cl2 (65 mL) at 0 °C was added DMP (6.84 g, 16.1 mmol, 1.2
equiv), and the reaction mixture was stirred for 1 h. After warming to
room temperature, the reaction mixture was stirred for a further 2 h.
The reaction was quenched by addition of a satd. solution of
NaHCO3/Na2S2O3 (1:1, 20 mL). Then, the reaction mixture was
extracted with CH2Cl2 (2 × 20 mL), and the combined organic layers
were washed with a satd. solution of NaHCO3/Na2S2O3 (1:1, 20 mL)
and dried (MgSO4). All volatile materials were removed under
reduced pressure, and the residue was taken up in Et2O and filtered.
The filtrate was concentrated under reduced pressure to give 11 (1.71
g, 13.4 mmol, quant.) as a light-yellow oil, which was directly used for
further reactions. 1H NMR (500 MHz, CDCl3) δ (ppm) = 9.56 (d, J
= 7.8 Hz, 1H, CHO), 6.92 (dt, J = 15.8, 7.0 Hz, 1H, 3-H), 6.19 (ddt, J
= 15.8, 7.8, 1.6 Hz, 1H, 2-H), 3.74 (s, 3H, OCH3), 3.38 (dd, J = 7.0,
1.6 Hz, 2H, 4-H); 13C{1H} NMR (126 MHz, CDCl3) δ (ppm) =
193.3 (CHO), 169.8 (C-1), 148.1 (C-3), 135.3 (C-2), 52.4 (OCH3),
1
colorless oil, with the Z-isomer in trace amounts (dr = 78:22, by H
NMR, 1′-H). Z-Isomer: Rf = 0.44 (hexanes/EtOAc 10:1); E-isomer
22: Rf = 0.35 (hexanes/EtOAc 10:1); [α]2D0 = −71 (c 1.0, CHCl3). 1H
NMR (500 MHz, CDCl3) δ (ppm) = 7.21−7.30 (m, 1H, 8-H), 6.26
(dd, J = 15.3, 10.9 Hz, 1H, 7-H), 6.07 (dd, J = 15.2, 9.7 Hz, 1H, 6-H),
5.86 (dd, J = 15.5, 2.8 Hz, 1H, 9-H), 3.73 (s, 3H, OCH3), 3.69 (s, 3H,
OCH3), 3.23 (dd, J = 9.8, 6.7 Hz, 1H, 5-H), 3.06 (t, J = 9.2 Hz, 1H, 5-
H*), 2.19−2.27 (m, 1H, 4-H), 2.16 (d, J = 7.1 Hz, 2H, 3-H), 1.03 (d,
J = 6.5 Hz, 3H, 1′-H*), 0.95 (d, J = 6.8 Hz, 3H, 1′-H), 0.14 (s, 9H,
Si(CH3)3); 13C{1H} NMR (126 MHz, CDCl3) δ (ppm) = 173.1
(COO), 172.9 (COO*), 167.4 (C-10), 167.3 (C-10*), 143.9 (C-8),
143.8 (C-8*), 138.5 (C-6*), 137.5 (C-6), 132.0 (C-7), 131.7 (C-7*),
121.4 (C-9*), 121.3 (C-9), 104.7 (C-2), 104.1 (C-2*), 87.1 (C-1*),
87.0 (C-1), 54.8 (C-5*), 53.4 (C-5), 52.2 (OCH3), 51.7 (OCH3),
35.3 (C-4), 35.1 (C-4*), 25.5 (C-3), 24.6 (C-3*), 17.5 (C-1′*), 16.5
37.4 (C-4); FT-IR (ATR): ν
(vw), 1737 (s), 1688 (vs), 1437 (m), 1399 (w), 1346 (w), 1265 (m),
1207 (m), 1168 (s), 1127 (m), 1013 (m), 980 (m), 934 (w), 892 (w),
̃
= 3006 (w), 2955 (w), 2846 (w), 2754
(C-1′), 0.2 (Si(CH3)3); FT-IR (ATR): ν = 2955 (m), 2847 (w), 2174
̃
(m), 1720 (s), 1645 (m), 1617 (m), 1435 (m), 1305 (m), 1249 (s),
1206 (s), 1160 (s), 1138 (s), 1034 (m), 1000 (s), 935 (w), 839 (vs),
7545
J. Org. Chem. 2021, 86, 7537−7551