T. Xu, C. Cuyamendous, S.L. Brown et al.
Tetrahedron 88 (2021) 132109
added to the reaction mixture via a syringe pump under argon
atmosphere over 5 h. Upon completion, the reaction mixture was
further stirred for 1 h before a solution of thioamide 40 (11.9 mg,
0.024 mmol, 1.0 eq) in deoxygenated anhydrous DCM (0.8 mL)
adding. The resulting mixture was stirred at 45 ꢁC (oil bath tem-
perature) in a sealed vial under argon atmosphere for 12 h before
concentration under reduced pressure. The crude material was
purified by silica gel flash chromatography (pet. ether/
EtOAc ¼ 10:1) to provide the title compound 43 (9.5 mg, 61%) as a
colourless oil. Rf: 0.60 (pet. ether/EtOAc ¼ 5:1). 1H NMR (500 MHz,
room temperature for 5 min. The mixture was then added ethyl
acetate (6 mL) and saturated brine (2 mL). The aqueous phase was
extracted by ethyl acetate (3 ꢂ 5 mL). The combined organic phase
was dried with anhydrous Na2SO4, filtered, and then concentrated
by rotary evaporation. The crude material was purified by flash
silica chromatography (pet. ether/EtOAc ¼ 4:1) to afford the title
compound 45 as a colourless oil (49.0 mg, 60%). Rf: 0.27 (pet. ether/
EtOAc ¼ 5:1). 1H NMR (500 MHz, CDCl3):
d 7.68e7.64 (m, 4H),
7.45e7.35 (m, overlapped, 7H), 6.75 (s, 1H), 6.58 (t, J ¼ 11.3 Hz, 1H),
6.04 (dt, J ¼ 15.5, 6.4 Hz, 1H), 5.62 (d, J ¼ 11.4 Hz, 1H), 4.20 (t,
J ¼ 5.7 Hz, 2H), 4.14(tt, J ¼ 7.9, 4.2 Hz, 1H), 3.62 (dd, J ¼ 10.2, 4.5 Hz,
1H), 3.53 (dd, J ¼ 10.2, 6.9 Hz,1H), 3.47 (dd, J ¼ 14.5, 3.9 Hz,1H), 3.19
(dd, J ¼ 14.4, 7.9 Hz, 1H), 2.77 (t, J ¼ 6.8 Hz, 2H), 2.54e2.48 (m, 2H),
2.34 (t, J ¼ 6.7 Hz, 2H), 1.75e1.68 (m, 4H), 1.05 (s, 9H), 0.75 (s,
CDCl3):
d 7.69e7.62 (m, 4H), 7.45e7.34 (m, 6H), 6.74 (s, 1H),
4.18e4.11 (m, overlapped, 3H), 3.63 (dd, J ¼ 10.2, 4.7 Hz, 1H), 3.54
(dd, J ¼ 10.2, 6.7 Hz, 1H), 3.39 (dd, J ¼ 14.5, 4.0 Hz, 1H), 3.11 (dd,
J ¼ 14.5, 7.8 Hz, 1H), 2.75 (t, J ¼ 7.2 Hz, 2H), 2.33 (t, J ¼ 7.0 Hz, 2H),
1.77e1.66 (m, 4H), 1.25 (t, J ¼ 7.1 Hz, 3H), 1.05 (s, 9H), 0.76 (s,
9H), ꢀ0.17 (s, 3H), ꢀ0.25 (s, 3H). 13C NMR (125 MHz, CDCl3):
d 173.5,
9H), ꢀ0.15 (s, 3H), ꢀ0.25 (s, 3H). 13C NMR (125 MHz, CDCl3):
d
173.7,
169.6, 168.1, 156.1, 144.6, 139.3, 135.59, 135.58, 133.4, 133.3, 129.65,
129.62,129.2 (C-15), 127.67, 127.66, 117.3, 112.9, 72.6, 67.2, 62.4, 38.1,
34.2, 31.8, 30.7, 29.2, 26.8, 25.8, 24.6, 19.2, 17.9, ꢀ4.9, ꢀ5.4. FTIR
167.1, 156.4, 135.62, 135.59, 133.30, 129.67, 129.65, 127.684, 127.678,
112.5, 72.8, 67.4, 60.3, 38.6, 34.2, 31.2, 28.8, 26.9, 25.8, 24.6, 19.2,
18.0, 14.3, ꢀ4.8, ꢀ5.3. FTIR (thin film)
n
2954, 2929, 2857, 1735,
(thin film) n 3070, 3050, 2953, 2929, 2893, 2857, 1736, 1695, 1640,
1472,1462,1428,1254,1186,1112,1075, 836, 824, 805, 777, 740, 702,
1602, 1525, 1471, 1428, 1389, 1361, 1252 cmꢀ1. HRMS (ESI): Calcu-
690, 505, 493 cmꢀ1. HRMS (ESI): Calculated for C35H54NO4SSiþ2
lated for C40H58NO6SSiþ2 [M þ H]þ 736.3518; found 736.3519.
26
23
[M þ H]þ 640.3307; found 640.3296. [
a
]
ꢀ111.1 (c ¼ 0.45, DCM).
[
a
]
D
ꢀ13.7 (c ¼ 0.99, DCM).
D
2-(6-Oxo-3,6-dihydro-2H-pyran-2-yl)ethyl 5-(2-((S)-2-((tert-
butyldimethylsilyl)oxy)-3-((tert-butyldiphenylsilyl)oxy)propyl)
thiazol-4-yl)pentanoate (44). To a solution of Mor-DalPhosAuOMs
(12) (26.0 mg, 0.0344 mmol, 0.01 equiv.) in anhydrous deoxygen-
ated DCM (7.0 mL) was added alkyne 5 (862 mg, 3.44 mmol, 1.03
equiv.). The resulting mixture was stirred at room temperature
under argon atmosphere for 30 min. Then a solution of 8-
methylquinoline N-oxide (11) (712 mg, 4.47 mmol, 1.34 equiv.)
(2Z,4E)-7-((5-(2-((S)-3-((tert-Butyldiphenylsilyl)oxy)-2-
hydroxypropyl)thiazol-4-yl)pentanoyl)oxy)hepta-2,4-dienoic
acid (46). Pyridinium p-toluenesulfonate (156 mg, 0.621 mmol,10.0
equiv.) was added to a solution of acid 45 (46 mg, 0.063 mmol, 1.0
equiv.) in MeOH (4.5 mL). The reaction mixture was stirred at
45e50 ꢁC for 27 h. Upon completion, the reaction mixture was
concentrated under reduced pressure and the residue was directly
loaded onto a silica column and purified by flash chromatography
using pet. ether/EtOAc ¼ 2:1 as eluent to afford the title compound
46 as a colourless oil (11.9 mg, 30%, BRSM 43%). Rf: 0.56 (pet. ether/
and methanesulfonic acid (268
mL, 4.13 mmol, 1.24 equiv.) in
degassed anhydrous DCM (6.9 mL) was added to the reaction
mixture via a syringe pump under argon atmosphere over 9 h.
Upon completion, the reaction mixture was further stirred for 1 h
before a solution of thioamide 40 (1.63 g, 3.34 mmol, 1.0 equiv.) in
deoxygenated anhydrous deoxygenated DCM (22 mL) was added.
The resulting mixture was stirred at 45 ꢁC (oil bath temperature) in
a sealed vial for 72 h under argon atmosphere before concentration
under reduced pressure. The crude material was purified by silica
gel flash chromatography (pet. ether/EtOAc ¼ 3:2) to provide the
title compound 44 (1.31 g, 52%, BRSM 57%) as a yellow oil. Rf: 0.52
EtOAc ¼ 1:1). 1H NMR (500 MHz, CDCl3):
d 7.68e7.62 (m, 4H),
7.45e7.32 (m, overlapped, 7H), 6.79 (s, 1H), 6.59 (t, J ¼ 11.4 Hz, 1H),
6.06 (dt, J ¼ 15.1, 6.2 Hz, 1H), 5.59 (d, J ¼ 11.4 Hz, 1H), 4.22 (t,
J ¼ 5.8 Hz, 2H), 4.15e4.07 (m, 1H), 3.72 (dd, J ¼ 10.3, 5.5 Hz, 1H),
3.67 (dd, J ¼ 9.7, 5.3 Hz, 2H), 3.31 (dd, J ¼ 15.6, 3.1 Hz, 1H), 3.20 (dd,
J ¼ 15.1, 8.7 Hz, 1H), 2.74 (t, J ¼ 7.0 Hz, 2H), 2.55e2.49 (m, 2H), 2.35
(t, J ¼ 6.6 Hz, 2H),1.76e1.63 (m, 4H),1.07 (s, 9H). 13C NMR (125 MHz,
CDCl3):
133.07, 129.76, 129.75, 129.1, 127.74, 127.72, 116.8, 112.8, 71.3, 66.8,
62.5, 36.3, 34.0, 31.9, 30.6, 28.8, 26.8, 24.4, 19.2. FTIR (thin film) n
d 173.6,170.1,167.7,156.1, 145.4,140.0,135.52, 135.51,133.10,
(pet. ether/EtOAc ¼ 1:1). 1H NMR (500 MHz, CDCl3):
d
7.69e7.62
(m, 4H), 7.46e7.33 (m, 6H), 6.94e6.82 (m, 1H), 6.75 (s, 1H), 6.04 (dt,
J ¼ 9.9, 1.7 Hz, 1H), 4.61e4.50 (m, 1H), 4.35e4.22 (m, 2H), 4.17e4.09
(m, 1H), 3.63 (dd, J ¼ 10.2, 4.7 Hz, 1H), 3.53 (dd, J ¼ 10.2, 6.7 Hz, 1H),
3.39 (dd, J ¼ 14.5, 3.9 Hz, 1H), 3.11 (dd, J ¼ 14.6, 7.8 Hz, 1H), 2.75 (t,
J ¼ 7.1 Hz, 2H), 2.43e2.31 (m, 2H), 2.34 (t, J ¼ 6.9 Hz, 2H), 2.16e2.09
(m, 1H), 2.04e1.95 (m, 1H), 1.78e1.64 (m, 4H), 1.05 (s, 9H), 0.76 (s,
3391, 3069, 2929, 2857, 1733, 1640, 1602, 1525, 1461, 1428, 1389,
1361, 1185, 1112, 999, 964, 939, 859, 824, 741, 703, 614, 593, 506,
434, 418 cmꢀ1. HRMS (ESI): Calculated for C34H44NO6SSiþ [M þ H]þ
622.2653; found 622.2625. [
a
]
D
24 ꢀ9.0 (c ¼ 0.69, DCM).
(S,6Z,8E)-3-(((tert-Butyldiphenylsilyl)oxy)methyl)-4,12-
dioxa-1(2,4)-thiazolacycloheptadecaphane-6,8-diene-5,13-
dione (48). To a mixture of acid 46 (12.9 mg, 0.0203 mmol, 1.0
equiv.) and solid NaHCO3 (419 mg, 4.99 mmol, 246 equiv.) in
anhydrous DCM (36 mL) was added 2-bromo-1-ethyl-pyridinium
tetrafluoroborate (47) (141 mg, 0.515 mmol, 24.6 equiv.). The re-
action mixture was stirred in the dark under argon atmosphere at
room temperature for 19 h. The reaction was quenched by addition
of distilled water (3.9 mL). The aqueous phase was separated and
extracted by ethyl acetate (4 ꢂ 8 mL). The combined organic phase
was dried with anhydrous Na2SO4, filtered, and then concentrated
by rotary evaporation. The crude material was purified by flash
silica chromatography (pet. ether/EtOAc ¼ 2:1) to afford the title
compound 48 as a colorless oil (9.4 mg, 75%). Rf: 0.73 (pet. ether/
9H), ꢀ0.15 (s, 3H), ꢀ0.25 (s, 3H). 13C NMR (125 MHz, CDCl3):
d 173.4,
167.2, 163.9, 156.3, 144.73, 144.72, 135.59, 135.56, 133.4, 133.3,
129.65,129.63,127.66, 127.65,121.5,112.6, 74.7, 72.7, 67.3, 59.8, 38.6,
34.02, 33.97, 31.2, 29.4 28.7, 26.8, 25.7, 24.5, 19.2, 17.9, ꢀ4.8, ꢀ5.3.
FTIR (thin film)
n 2953, 2929, 2856, 1731, 1472, 1462, 1428, 1389,
1361, 1248 cmꢀ1. HRMS (ESI): Calculated for C40H58NO6SSiþ2 [M þ
H]þ 736.3518; found 736.3494. [
(2Z,4E)-7-((5-(2-((S)-2-((tert-Butyldimethylsilyl)oxy)-3-
((tert-butyldiphenylsilyl)oxy)propyl)-thiazol-4-yl)pentanoyl)
oxy)hepta-2,4-dienoic acid (45). Potassium bis(trimethylsilyl)
a]
ꢀ14.3 (c ¼ 1.05, DCM).
25
D
amide solution (145 mL, 1.0 M in THF, 0.145 mmol, 1.3 equiv.) was
added dropwise to a solution of thiazole 44 (82.2 mg, 0.112 mmol,
1.0 equiv.) in anhydrous THF (2.0 mL) at ꢀ78 ꢁC. The reaction
mixture was stirred at that temperature under argon atmosphere
EtOAc ¼ 1:1). 1H NMR (600 MHz, CDCl3):
d 7.70e7.64 (m, 4H),
7.45e7.36 (m, 6H), 7.19 (dd, J ¼ 15.4,11.3 Hz,1H), 6.73 (s, 1H), 6.46 (t,
J ¼ 11.4 Hz, 1H), 5.93 (ddd, J ¼ 15.3, 8.9, 5.6 Hz, 1H), 5.51e5.47 (m,
overlapped, 2H), 4.26 (td, J ¼ 10.6, 10.1, 2.8 Hz, 1H), 4.22e4.18 (m,
1H), 3.84 (dd, J ¼ 10.8, 5.1 Hz,1H), 3.79 (dd, J ¼ 10.8, 4.8 Hz,1H), 3.33
for 2 h. Aqueous sulfuric acid (193 mL, 2 vol%) was added to the
reaction mixture dropwise at ꢀ78 ꢁC, and then the resulting
mixture was allowed to warm up to room temperature and stir at
10