E
C. García-Ruiz et al.
Special Topic
Synthesis
mmol 1.5 equiv). After 30 min, the reaction was complete and the sol-
vent was removed under reduced pressure. The resulting crude resi-
due was purified by flash column chromatography (silica gel, 20%
EtOAc in hexanes) to provide the α,β-unsaturated diepoxy ester 14
(100 mg, 60% over 2 steps) as a pale yellow oil.
[dd, J = 4.3, 2.1 Hz, 1 H, CH2CH(O)CH], 2.93 [dd, J = 4.3, 2.1 Hz, 1 H,
CH(O)CHCH=], 2.17 (s, 3 H, OCOCH3), 0.89 [s, 9 H, (CH3)3CSi], 0.07 [s, 3
H, (CH3)2Si], 0.06 [s, 3 H, (CH3)2Si].
13C NMR (100 MHz, CDCl3): δ = 130.19, 129.83, 63.61, 61.98, 57.97,
56.07, 54.93, 53.10, 30.91, 25.84, 20.93, 18.33, –5.36, –5.37.
HRMS (H-ESI): m/z [M + H]+ calcd for C16H29O5Si: 329.1784; found:
[α]D25 –12.4 (c 0.7, CH2Cl2); Rf = 0.64 [silica gel, 40% EtOAc in hexanes].
1H NMR (400 MHz, CDCl3): δ = 6.64 (dd, J = 15.7, 7.2 Hz, 1 H, CH=CH-
CO), 6.15 (dd, J = 15.7, 0.7 Hz, 1 H, CH=CHCO), 4.19 (q, J = 7.1 Hz, 2 H,
CH2CH3), 3.87 (dd, J = 12.3, 2.8 Hz, 1 H, SiOCH2), 3.74 (dd, J = 12.3, 3.9
Hz, 1 H, SiOCH2), 3.47 [ddd, J = 7.2, 2.0, 0.7 Hz, 1 H, CH(O)CHCH=], 3.10
[ddd, J = 3.9, 2.7, 2.1 Hz, 1 H, CH2CH(O)], 3.04 [dd, J = 4.0, 2.1 Hz, 1 H,
CH2CH(O)CH], 3.01 [dd, J = 4.0, 2.0 Hz, 1 H, CH(O)CHCH=], 1.28 (t, J =
7.1 Hz, 3 H, CH2CH3), 0.88 [s, 9 H, (CH3)3CSi], 0.06 [s, 3 H, (CH3)2Si],
0.05 [s, 3 H, (CH3)2Si].
13C NMR (100 MHz, CDCl3): δ = 165.41, 143.02, 124.71, 61.82, 60.69,
58.50, 56.24, 53.77, 52.62, 25.82, 18.32, 14.18, –5.37, –5.39.
HRMS (H-ESI): m/z [M + H]+ calcd for C16H29O5Si: 329.1784; found:
329.1780.
329.1776.
Epoxy Amide 18
To a suspension of PCC (1.6 g, 7.4 mmol, 1.5 equiv) in CH2Cl2 (20 mL)
was added anhydrous NaOAc (1.6 g, 19.8 mmol, 4.0 equiv) followed
by a solution of cis-alcohol 11 (1.0 g, 4.94 mmol, 1.0 equiv) in CH2Cl2
(15 mL). The reaction mixture was stirred at r.t. for 6 h and the result-
ing crude was filtered off through a pad of SiO2 and washed with Et2O.
The solvent was removed under vacuum and the crude aldehyde 17
was used in the next step without further purification. The crude al-
dehyde was reacted with sulfonium salt 2 (1.3 g, 4.0 mmol, 1.1 equiv)
and NaOH (1.2 mL, 3.0 M aq solution, 3.6 mmol, 1.0 equiv), according
to the procedure described above for the synthesis of diepoxy amide
13, to yield epoxy amide 18 (800 mg, 40% over two steps) as a pale
yellow oil.
Allylic Alcohol 15
At –78 °C, DIBAL-H (1.15 mL, 1.0 M in toluene, 1.15 mmol, 2.5 equiv)
was added to a solution of ester 14 (151 mg, 0.46 mmol, 1.0 equiv) in
CH2Cl2 (10 mL). After 30 min, the reaction was complete and was al-
lowed to warm to 0 °C. At this temperature, the mixture was diluted
with EtOAc and sat. aq Na+/K+ tartrate solution. After 2 h of vigorous
stirring, the aqueous phase was extracted twice with EtOAc and the
organic layer washed with H2O and brine, then dried over anhydrous
MgSO4 and filtered. The solvent was then removed carefully under re-
duced pressure at low temperature. Purification by flash column
chromatography (silica gel, 20% EtOAc in hexanes) of the resulting
crude residue rendered the allylic alcohol 15 (100 mg, 76% yield) as a
pale yellow oil.
[α]D25 –11.1 (c 0.8, CH2Cl2); Rf = 0.43 [silica gel, 40% EtOAc in hexanes].
1H NMR (400 MHz, CDCl3): δ = 6.09 (ddd, J = 15.4, 4.4, 4.0 Hz, 1 H,
CH2CH=CH), 5.48 (ddt, J = 15.4, 8.1, 2.0 Hz, 1 H, CH2CH=CH), 4.27 (ddd,
J = 10.2, 4.9, 3.1 Hz, 1 H, CONCH), 4.17 (dt, J = 3.7, 1.7 Hz, 2 H, SiOCH2),
3.99 (ddd, J = 9.1, 5.2, 1.4 Hz, 1 H, OCH2CH), 3.89–3.84 (m, 1 H,
OCH2CH), 3.58 [dd, J = 8.1, 1.7 Hz, 1 H, =CHCH(O)CH], 3.51 [d, J = 1.9
Hz, 1 H, CH(O)CHCO], 2.53 (ddd, J = 13.2, 7.0, 5.1 Hz, 1 H, SCH2CH2),
2.40 (ddd, J = 13.4, 8.9, 6.6 Hz, 1 H, SCH2CH2), 2.05 (s, 3 H, CH3S), 2.03–
1.96 (m, 1 H, SCH2CH2), 1.78–1.71 (m, 1 H, SCH2CH2), 1.61 (s, 3 H,
CH3C), 1.51 (s, 3 H, CH3C), 0.87 [s, 9 H, (CH3)3CSi], 0.03 [s, 6 H,
(CH3)2Si].
[α]D25 –20.2 (c 0.4, CH2Cl2); Rf = 0.35 [silica gel, 30% EtOAc in hexanes].
13C NMR (100 MHz, CDCl3): δ = 163.42, 137.15, 124.45, 95.89, 67.01,
62.51, 57.82, 55.85, 55.44, 34.27, 30.79, 26.27, 25.88, 22.99, 18.32,
15.81, –5.37, –5.38.
HRMS (H-ESI): m/z [M + H]+ calcd for C20H38NO4SSi: 416.2291; found:
416.2286.
1H NMR (400 MHz, CDCl3): δ = 6.11 (dt, J = 15.6, 5.1 Hz, 1 H,
CH=CHCH2), 5.49 (ddt, J = 15.6, 7.9, 1.7 Hz, 1 H, CH=CHCH2), 4.19 (d,
J = 3.9 Hz, 2 H, =CHCH2OH), 3.88 (dd, J = 12.2, 2.8 Hz, 1 H, SiOCH2),
3.74 (dd, J = 12.2, 4.0 Hz, 1 H, SiOCH2), 3.40 [dd, J = 7.9, 2.1 Hz, 1 H,
(O)CHCH=], 3.09 [ddd, J = 4.0, 2.8, 2.1 Hz, 1 H, CH2CH(O)CH], 3.00 [dd,
J = 4.3, 2.1 Hz, 1 H, CH2CH(O)CH], 2.93 [dd, J = 4.3, 2.1 Hz, 1 H,
CH(O)CHCH=], 1.61 (br s, 1 H, OH), 0.89 [s, 9 H, (CH3)3CSi], 0.06 [s, 3 H,
(CH3)2Si], 0.05 [s, 3 H, (CH3)2Si].
13C NMR (100 MHz, CDCl3): δ = 135.29, 127.24, 62.57, 62.05, 58.00,
56.05, 55.25, 53.25, 25.84, 18.34, –5.35, –5.36.
HRMS (H-ESI): m/z [M + H]+ calcd for C14H27O4Si: 287.1679; found:
287.1685.
Diepoxy Amide 19
To a solution of epoxy amide 18 (100 mg, 0.24 mmol, 1.0 equiv) in dry
THF (6 mL) was added dropwise Red-Al (0.15 mL, 60% w/v, 0.53
mmol, 2.2 equiv) at 0 °C. After 1 h at 0 °C, the reaction mixture was
quenched by the addition of sat. aq NH4Cl solution. After separation
of both layers, the aqueous phase was extracted with EtOAc, the or-
ganic extracts were washed with brine and dried over MgSO4, and the
solvent was evaporated under reduced pressure. The resulting crude
epoxy aldehyde was used in the next step without further purifica-
tion The crude aldehyde was reacted with sulfonium salt 2 (85 mg,
0.26 mmol, 1.1 equiv) and NaOH (0.04 mL, 5.0 M aq solution, 0.24
mmol, 1.0 equiv), according to the general procedure described above
for the synthesis of diepoxy amide 13, to yield diepoxy amide 19 (36
mg, 95% over two steps) as a yellow oil.
Acetyl Derivative 16
To a solution of the allylic alcohol 15 (32 mg, 0.1 mmol, 1.0 equiv) in
py (3 mL) was added Ac2O (0.4 mL, 4.5 mmol, 40 equiv) at r.t. After 12
h at the same temperature, the solvent was removed under vacuum
and the crude residue was purified by flash column chromatography
(silica gel, 10% EtOAc in hexanes) to furnish acetate 16 (27 mg, 73%
yield) as a pale yellow oil.
[α]D25 –21.4 (c 1.0, CH2Cl2); Rf = 0.26 [silica gel, 40% EtOAc in hexanes].
1H NMR (400 MHz, CDCl3): δ = 6.04 (dt, J = 15.4, 4.3 Hz, 1 H,
CH2CH=CH), 5.50–5.40 (m, 1 H, CH2CH=CH), 4.34–4.27 (m, 1 H,
CONCH), 4.18 (dd, J = 4.2, 1.9 Hz, 2 H, SiOCH2), 4.01 (dd, J = 8.7, 5.7 Hz,
1 H, OCH2CH), 3.90 (d, J = 9.2 Hz, 1 H, OCH2CH), 3.58 [d, J = 1.9 Hz, 1 H,
CH(O)CHCO], 3.43 [dd, J = 8.0, 1.9 Hz, 1 H, =CHCH(O)CH], 3.36 [dd, J =
3.3, 1.9 Hz, 1 H, CH(O)CHCO], 3.05–3.02 [m, 1 H, =CHCH(O)CH], 2.58
[α]D25 –15.3 (c 0.4, CH2Cl2); Rf = 0.91 [silica gel, 40% EtOAc in hexanes].
1H NMR (400 MHz, CDCl3): δ = 6.03 (dtd, J = 15.6, 5.8, 0.6 Hz, 1 H,
CH=CHCH2), 5.51 (ddt, J = 15.6, 7.8, 1.5 Hz, 1 H, CH=CHCH2), 4.58 (dd,
J = 5.8, 1.5 Hz, 2 H, =CHCH2OH), 3.92–3.83 (m, 1 H, SiOCH2), 3.74 (dd,
J = 12.2, 4.0 Hz, 1 H, SiOCH2), 3.38 [dd, J = 8.0, 1.9 Hz, 1 H,
CH(O)CHCH=], 3.09 [ddd, J = 4.0, 2.8, 2.1 Hz, 1 H, CH2CH(O)CH], 2.99
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H