The Journal of Organic Chemistry
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δ 8.36 (br d, J = 5.0 Hz, 1Har), 7.53 (td, J = 7.7, 1.7 Hz, 1Har), 7.26 (t, J =
4.0 Hz, 1Har), 7.06 (br dd, J = 6.8, 5.6 Hz, 1Har), 6.51 (d, J = 7.9 Hz, 1H
(NH)), 5.39−5.29 (m, 2H (2CH)), 4.32−4.24 (m, 1H (CH−N)),
3.70−3.56 (m, 3H (2CH−O and A part of a CH2−S AB system), 3.43
(dd, B part of an AB system, JAB = 15.1 Hz, J = 3.6 Hz, 1H (CH2−S)),
2.96 (br s, 2H (2OH)) 2.15 (t, J = 7.4 Hz, 2H (CH2−CO)), 2.05−1.97
(m, 4H (2CH2−CC)), 1.72−1.61 (m, 2H), 1.61−1.52 (m, 3H),
1.51−1.40 (m, 2H), 1.38−1.20 (m, 53H), 0.88 (t, J = 6.8 Hz, 6H
(2CH3)). 13C NMR (101 MHz, CDCl3) δ 174.0 (CO), 159.3 (Car),
149.0 (CHar), 136.9 (CHar), 130.0 (2CH), 123.2 (CHar), 120.3
(CHar), 74.9 (CH−O), 72.9 (CH−O), 52.9 (CH−N), 37.1 (CH2−
CO), 32.6 (CH2), 32.1 (CH2−S), 32.1 (CH2), 30.0 (CH2), 29.9
(3CH2), 29.8 (3CH2), 29.7 (CH2), 29.5 (4CH2), 29.4 (CH2), 27.4
(2CH2−CC), 26.2 (CH2), 25.9 (CH2), 22.9 (CH2), 22.8 (CH2), 14.3
(2CH3). HRMS (ESI-TOF) m/z: [M + H]+ calcd for C47H86N2O3S,
759.6437; found, 759.6434.
J = 4.2 Hz, 1H (CH2−S)), 3.07 (dd, B part of an AB system, JAB =
13.9 Hz, J = 8.4 Hz, 1H (CH2−S)), 2.77 (br s, 1H (OH)), 2.11 (t, J = 7.6
Hz, 2H (CH2−CO)), 2.03 (q, J = 6.8 Hz, 2H (CH2−CC)), 1.60−
1.51 (m, 2H), 1.37−1.22 (m, 30H), 0.87 (t, J = 6.7 Hz, 6H (2CH3)). 13
C
NMR (101 MHz, CDCl3) δ 174.4 (CO), 135.5 (Car), 134.9 (CH
(5)), 130.0 (CHar), 129.3 (CHar), 128.2 (CH (4)), 126.8 (CHar),
74.6 (CH−O), 54.1 (CH−N), 36.8 (CH2−CO), 34.4 (CH2−S), 32.5
(CH2), 32.1 (CH2), 31.8 (CH2), 29.9 (CH2), 29.8 (2CH2), 29.7 (CH2),
29.5 (CH2), 29.4 (CH2), 29.3 (2CH2), 29.2 (CH2), 25.8 (CH2), 22.9
(CH2), 22.8 (CH2), 14.3 (CH3), 14.2 (CH3). HRMS (ESI-TOF) m/z:
[M + H]+ calcd for C32H56NO2S, 518.4032; found, 518.4026. Mp: 75−
77 °C.
N-((2R,3R,E)-1-((2-(Hydroxymethyl)phenyl)thio)-3-
(methoxymethoxy)octadec-4-en-2-yl) octanamide (18e).
N-((2R,3R,E)-3-(Methoxymethoxy)-1-(phenylthio)octadec-4-
en-2-yl)octanamide (18d).
Ring-opened product 18e was synthesized from 16 (36.8 mg,
0.082 mmol), 2-mercaptobenzyl alcohol (14 mg, 0.098 mmol), and
DBU (13 μL, 0.087 mmol) in MeCN (800 μL) according to General
Procedure 1 (150 W, 689.5 kPa, 100 °C) to almost complete conversion
after 20 min. After flash chromatographic purification (silica gel, hexane/
AcOEt 8:2), pure product 18e was isolated as a white solid (29.0 mg,
60% yield, 71% conversion). [α]20D −51.7 (c 2.94, CHCl3). IR (film):
Octanamide 18d was synthesized from 16 (28.3 mg, 0.063 mmol),
thiophenol (8 μL, 0.078 mmol), and DBU (10 μL, 0.067 mmol) in
MeCN (600 μL) according to General Procedure 1 (150 W, 689.5 kPa,
100 °C) to give complete conversion after 5 min. After flash chro-
matographic purification (silica gel, hexane/AcOEt 8.5:1.5), pure
1
ν = 3291, 3063, 2955, 2924, 2853, 1647, 1545, 1466, 1024 cm−1. H
NMR (400 MHz, CDCl3) δ 7.43 (d, J = 7.4 Hz, 2Har), 7.25−7.18 (m,
2Har), 6.00 (d, J = 8.5 Hz, 1H (NH)), 5.76−5.65 (dt, J = 15.2, 6.6 Hz, 1H
(CH (5))), 5.25 (dd, J = 15.2, 6.6 Hz, 1H (CH (4))), 4.88 (d, A
part of an AB system, JAB = 12.7 Hz, 1H (CH2 benz)), 4.66−4.60 (m, 2H
(B part of a CH2 benz AB system and A part of a CH2 (MOM) AB
system), 4.51 (d, B part of an AB system, JAB = 6.6 Hz, 1H (CH2
(MOM))), 4.21−4.09 (m, 2H (CH−N and CH−O))), 3.35 (s, 3H
(CH3 (MOM))), 3.25 (dd, A part of an AB system, JAB = 13.8 Hz, J = 2.4
Hz, 1H (CH2−S))), 3.07 (dd, B part of an AB system, JAB = 13.8 Hz, J =
7.4 Hz, 1H (CH2−S))), 2.95 (br s, 1H (OH)), 2.06−1.97 (m, 4H
(CH2−CO and CH2−CC)), 1.54−1.47 (m, 2H), 1.36−1.22 (m,
30H), 0.89−0.84 (m, 6H (2CH3)). 13C NMR (101 MHz, CDCl3) δ
173.4 (CO), 142.0 (Car), 137.3 (CH (5)), 134.4 (Car), 131.2
(CHar), 129.6 (CHar), 128.4 (CHar), 127.2 (CHar), 125.8 (CH (4)),
94.3 (CH2 (MOM)), 78.5 (CH−O), 63.2 (CH2 benz), 55.9 (CH3
(MOM)), 52.3 (CH−N), 36.8 (CH2−CO or CH2−CC), 35.6
(CH2−S), 32.5 (CH2−CO or CH2−CC), 32.1 (CH2), 31.8 (CH2),
29.8 (3CH2), 29.6 (CH2), 29.5 (CH2), 29.4 (CH2), 29.3 (CH2), 29.2
(2CH2), 25.6 (CH2), 22.8 (CH2), 22.8 (CH2), 14.3 (CH3), 14.2 (CH3).
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C35H61NO4S, 592.4400;
found, 592.4385. Mp: 62−64 °C.
product 18d was isolated as a colorless oil (31.8 mg, 90%). [α]20
D
−68.5 (c 1.05, CHCl3). IR (film): ν = 3292, 3053, 2949, 2924, 2853,
1
1646, 1546, 1480−1430,1027 cm−1. H NMR (500 MHz, CDCl3) δ
7.38 (d, J = 7.3 Hz, 2Har), 7.30−7.25 (m, 2Har), 7.17 (t, J = 7.4 Hz, 1Har),
5.73 (dt, J = 15.4, 6.9 Hz, 1H (CH (5))), 5.68 (d, J = 8.9 Hz, 1H
(NH)), 5.29 (dd, J = 15.4, 7.7 Hz, 1H (CH (4))), 4.66 (d, A part of an
AB system, JAB = 6.6 Hz, 1H (CH2 (MOM))), 4.52 (d, B part of an AB
system, JAB = 6.6 Hz, 1H (CH2 (MOM))), 4.30−4.23 (m, 1H (CH−
N)), 4.21−4.17 (m, 1H (CH−O)), 3.36 (s, 3H (CH3 (MOM))), 3.21
(d, J = 5.7 Hz, 2H (CH2−S)), 2.08−2.01 (m, 4H (CH2−CO and CH2−
CC)), 1.57−1.51 (m, 2H), 1.38−1.23 (m, 30H), 0.88 (t, J = 6.9 Hz,
3H (CH3)), 0.87 (t, J = 6.9 Hz, 3H (CH3)). 13C NMR (101 MHz,
CDCl3) δ 172.8 (CO), 137.4 (CH (5)), 136.6 (Car), 129.5 (CHar),
129.1 (CHar), 126.3 (CHar or CH (4)), 126.0 (CHar or CH (4)),
94.2 (CH2 (MOM)), 78.0 (CH−O), 55.9 (CH3 (MOM)), 52.0 (CH−
N), 37.0 (CH2−CO or CH2−CC), 34.5 (CH2−S), 32.5 (CH2−CO
or CH2−CC), 32.1 (CH2), 31.8 (CH2), 29.8 (3CH2), 29.6 (CH2),
29.5 (CH2), 29.4 (2CH2), 29.2 (2CH2), 25.7 (CH2), 22.8 (2CH2), 14.3
(CH3), 14.2 (CH3). HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C34H60NO3S, 562.4294; found, 562.4296.
N-((2R,3R,E)-3-Hydroxy-1-((2-(hydroxymethyl)phenyl)thio)-
octadec-4-en-2-yl)octanamide (19e).
N-((2R,3R,E)-3-Hydroxy-1-(phenylthio)octadec-4-en-2-yl)-
octanamide (19d).
To a solution of 18d (24.6 mg, 0.044 mmol) in MeOH (2 mL) was
added 37% aq hydrochloric acid (3 drops). The resulting solution was
heated to 64 °C and stirred at this temperature for 1 h. Then, the
reaction mixture was allowed to reach room temperature to remove the
volatiles under reduced pressure. The resulting residue was purified by
flash chromatography (silica gel, hexane/AcOEt 8.5:1.5) to afford
alcohol 19d as a pale yellow solid (17.0 mg, 75%). [α]20D −29.5 (c 1.57,
CHCl3). IR (film): ν = 3291, 3075, 2958, 2921, 2851, 1647, 1542,
1490−1365 cm−1. 1H NMR (400 MHz, CDCl3) δ 7.36 (d, J = 7.8 Hz,
2Har), 7.29 (t, J = 7.6 Hz, 2Har), 7.20 (t, J = 7.3 Hz, 1Har), 5.80 (d, J =
7.0 Hz, 1H (NH)), 5.74 (dt, J = 15.4, 6.8 Hz, 1H (CH (5))), 5.43 (dd,
J = 15.4, 6.6 Hz, 1H (CH (4))), 4.27−4.23 (m, 1H (CH−O)), 4.12−
4.03 (m, 1H (CH−N)), 3.19 (dd, A part of an AB system, JAB = 13.9 Hz,
To a solution of 18e (24.3 mg, 0.041 mmol) in MeOH (1.5 mL) was
added 37% aq hydrochloric acid (3 drops). The mixture was heated to
64 °C and stirred at this temperature for 1 h. Then, the reaction mixture
was allowed to reach room temperature to remove the volatiles under
reduced pressure. The resulting residue was purified by flash
chromatography (silica gel, hexane/AcOEt 7:3) to afford diol 19e as a
colorless oil (10.9 mg, 49%). IR (film): ν = 3277, 3088, 2955, 2921,
2851, 1647, 1554, 1466, 1435, 1036 cm−1. 1H NMR (500 MHz, CDCl3)
δ 7.46−7.41 (m, 2Har), 7.28−7.22 (m, 2Har), 6.08 (br d, J = 5.8 Hz, 1H
(NH)), 5.77−5.68 (m, 1H (CH (5))), 5.44−5.37 (m, 1H (CH
(4))), 4.86 (d, A part of an AB system, JAB = 12.4 Hz, 1H (CH2 benz)),
4.69 (d, B part of an AB system, JAB = 12.4 Hz, 1H (CH2 benz)),
4.26−4.20 (m, 1H (CH−O)), 4.05−3.97 (m, 1H (CH−N)), 3.25−3.15
3011
dx.doi.org/10.1021/jo500061w | J. Org. Chem. 2014, 79, 2993−3029