The Journal of Organic Chemistry
Article
4j as a colorless oil (835 mg, 39% yield). 1H NMR (500 MHz, CDCl3):
δ 5.34 (t, J = 7.1 Hz, 1H), 5.08 (t, J = 7.1 Hz, 1H), 4.14 (d, J = 7.1 Hz,
2H), 4.08 (s, 2H), 2.11 (t, J = 7.1 Hz, 2H), 2.08−2.04 (m, 2H), 1.68 (d,
J = 2.3 Hz, 6H), 1.60 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ
173.7, 142.9, 132.1, 123.8, 119.2, 67.9, 66.3, 39.7, 26.4, 25.8, 17.8, 16.6.
Conversion of 4j to 1j afforded a colorless oil (468 mg, 38% yield). 1H
NMR (500 MHz, CDCl3): δ 5.43 (ddt, J = 8.3, 7.0, 1.3 Hz, 1H), 5.15−
5.08 (m, 1H), 4.68 (d, J = 2.6 Hz, 2H), 4.48 (dt, J = 8.3, 3.5 Hz, 1H),
4.37 (t, J = 8.8 Hz, 1H), 4.29 (dd, J = 9.2, 3.1 Hz, 1H), 4.17 (qd, J = 11.5,
6.9 Hz, 2H), 2.46 (heptd, J = 7.1, 3.9 Hz, 1H), 2.17−2.10 (m, 2H), 2.07
(dd, J = 9.4, 6.1 Hz, 2H), 1.71 (d, J = 1.4 Hz, 3H), 1.70 (d, J = 1.4 Hz,
3H), 1.62 (s, 3H), 0.95 (d, J = 7.0 Hz, 3H), 0.90 (d, J = 6.9 Hz, 3H).
13C{1H} NMR (126 MHz, CDCl3): δ 170.5, 154.2, 141.8, 131.9, 124.0,
3.37−3.30 (m, 2H), 2.82 (dd, J = 13.5, 9.6 Hz, 1H), 2.66−2.58 (m,
1H), 1.06 (d, J = 6.9 Hz, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ
174.4, 153.2, 139.9, 135.0, 129.6, 129.2, 127.7, 115.6, 73.9, 67.0, 55.8,
41.8, 37.7, 13.9. HRMS (DART-Orbitrap): m/z [M + H]+ calcd for
C16H20NO4, 290.1386; found, 290.1398.
(S)-3-((2S,3R)-2-Hydroxy-3-isopropylpent-4-enoyl)-4-isopropy-
loxazolidin-2-one (2e). Following the procedure for rearrangement of
1d, 1e afforded 2e (71% yield, >30:1 selectivity). 1H NMR (500 MHz,
CDCl3): δ 5.70 (dt, J = 17.1, 10.1 Hz, 1H), 5.23 (t, J = 9.8 Hz, 1H), 5.08
(dd, J = 10.3, 2.2 Hz, 1H), 5.02 (dd, J = 17.1, 2.2 Hz, 1H), 4.33 (q, J =
4.7 Hz, 1H), 4.24 (d, J = 4.8 Hz, 2H), 3.18 (d, J = 10.2 Hz, 1H), 2.39
(heptd, J = 7.0, 3.7 Hz, 1H), 2.24 (dddd, J = 19.2, 13.1, 8.3, 3.5 Hz, 2H),
0.92 (dd, J = 6.9, 1.4 Hz, 6H), 0.89 (d, J = 6.9 Hz, 6H). 13C{1H} NMR
(126 MHz, CDCl3): δ 175.0, 154.4, 134.5, 118.8, 71.9, 64.3, 59.1, 56.5,
28.7, 26.9, 21.5, 18.2, 16.7, 14.8. HRMS (DART-Orbitrap): m/z [M +
H]+ calcd for C14H24NO4, 270.1670; found, 270.1712.
120.0, 69.5, 68.0, 64.5, 58.3, 39.8, 28.4, 26.5, 25.8, 18.1, 17.8, 16.7, 14.8.
HRMS (DART-Orbitrap): m/z [M + H]+ calcd for C18H30NO4,
324.2169; found, 324.2185.
(S)-3-((2S,3R)-2-Hydroxy-3-methylpent-4-enoyl)-4-isopropyloxa-
zolidin-2-one (2d). To a solution of 1d (0.40 mmol, 96.4 mg) in
CH2Cl2 (1.0 mL) was added n-Bu2BOTf (0.80 mmol, 800 μL) as 1.0 M
solution in CH2Cl2, and the reaction was stirred at 0 °C for 5 min.
Triethyamine (1.2 mmol, 168 μL) was added. The reaction was
warmed to rt and stirred for an additional 3 h. The reaction was
quenched with saturated NH4Cl and extracted three times with
CH2Cl2. The organic extracts were dried over MgSO4 and concentrated
in vacuo. Flash chromatography (20% ethyl acetate/hexanes) afforded
2d and its minor isomer as a colorless oil (78.9 mg, 82% yield, 15:1
selectivity). 1H NMR (500 MHz, CDCl3): δ 5.86 (ddd, J = 17.6, 10.3,
7.6 Hz, 1H), 5.13−5.02 (m, 3H), 4.38 (dt, J = 7.2, 3.4 Hz, 1H), 4.30 (t, J
= 8.4 Hz, 1H), 4.26 (dd, J = 9.1, 2.8 Hz, 1H), 3.31 (d, J = 8.9 Hz, 1H),
2.61−2.54 (m, 1H), 2.44 (heptd, J = 7.2, 3.7 Hz, 1H), 1.03 (d, J = 6.8
Hz, 3H), 0.92 (d, J = 7.0 Hz, 3H), 0.88 (d, J = 7.0 Hz, 3H). 13C{1H}
NMR (126 MHz, CDCl3): δ 174.3, 153.9, 140.0, 115.5, 73.8, 64.2, 59.2,
41.8, 28.4, 18.1, 14.6, 13.9. HRMS (DART-Orbitrap): m/z [M + H]+
calcd for C12H20NO4, 242.1387; found, 242.1399.
(S)-4-Benzyl-3-((S)-2-hydroxypent-4-enoyl)oxazolidin-2-one (2a).
Following the procedure for rearrangement of 1d, 1a afforded 2a and its
minor isomer as a colorless oil (90% yield, 2:1 selectivity). Major
product 1H NMR (500 MHz, CDCl3): δ 7.35 (dd, J = 8.1, 6.5 Hz, 2H),
7.32−7.27 (m, 1H), 7.24−7.19 (m, 2H), 5.87 (ddt, J = 17.2, 10.2, 7.1
Hz, 1H), 5.21−5.09 (m, 3H), 4.66 (ddt, J = 10.0, 6.7, 3.3 Hz, 1H),
4.31−4.23 (m, 2H), 3.55 (d, J = 7.9 Hz, 1H), 3.32 (dd, J = 13.5, 3.3 Hz,
1H), 2.84 (dd, J = 13.5, 9.4 Hz, 1H), 2.62 (dddt, J = 14.3, 7.1, 4.7, 1.3
Hz, 1H), 2.46 (dtt, J = 14.2, 7.1, 1.2 Hz, 1H). 13C{1H} NMR (126
MHz, CDCl3): δ 174.1, 153.4, 134.9, 133.0, 129.6, 129.2, 127.7, 118.8,
70.4, 67.1, 55.7, 38.4, 37.7. Minor product 1H NMR (500 MHz,
CDCl3): δ 7.35 (dd, J = 8.1, 6.5 Hz, 2H), 7.32−7.27 (m, 1H), 7.24−
7.19 (m, 2H), 5.87 (ddt, J = 17.1, 10.1, 7.1 Hz, 1H), 5.23−5.14 (m,
3H), 4.75 (ddt, J = 9.8, 8.1, 3.5 Hz, 1H), 4.31 (t, J = 8.6 Hz, 1H), 4.24
(dd, J = 9.2, 3.4 Hz, 1H), 3.35−3.25 (m, 2H), 2.74 (dd, J = 13.4, 9.8 Hz,
1H), 2.67 (dddd, J = 11.3, 5.8, 2.5, 1.2 Hz, 1H), 2.53−2.45 (m, 1H).
13C{1H} NMR (126 MHz, CDCl3): δ 174.7, 153.1, 134.9, 132.6, 129.5,
(S)-3-((2S,3S)-2-Hydroxy-3-phenylpent-4-enoyl)-4-isopropyloxa-
zolidin-2-one (2f). To a solution of 1f (0.040 mmol, 12.1 mg) in
CH2Cl2 (1.0 mL) was added n-Bu2BOTf (0.080 mmol, 80 μL) as 1.0 M
solution in CH2Cl2 followed by stirring at −78 °C for 5 min.
Triethylamine (0.12 mmol, 17 μL) was added. The reaction was
warmed to rt and stirred for an additional 3 h. The reaction was
quenched with saturated NH4Cl and extracted three times with
CH2Cl2. The organic extracts were dried over MgSO4 and concentrated
in vacuo. Flash chromatography (20% ethyl acetate/hexanes) afforded
1
2f and its minor isomer (11.2 mg, 91% yield, >30:1 selectivity). H
NMR (500 MHz, CDCl3): δ 7.35−7.29 (m, 2H), 7.29−7.22 (m, 3H),
6.19 (ddd, J = 17.1, 10.2, 8.2 Hz, 1H), 5.58 (dd, J = 9.2, 6.0 Hz, 1H),
5.20 (dt, J = 17.1, 1.3 Hz, 1H), 5.17 (dt, J = 10.2, 1.2 Hz, 1H), 4.33−
4.23 (m, 3H), 3.78−3.71 (m, 1H), 3.21 (d, J = 9.2 Hz, 1H), 2.40 (heptd,
J = 7.0, 3.5 Hz, 1H), 0.90 (d, J = 7.0 Hz, 3H), 0.88 (d, J = 6.9 Hz, 3H).
13C{1H} NMR (126 MHz, CDCl3): δ 173.7, 154.0, 138.9, 137.4, 128.7,
128.6, 127.5, 117.3, 73.7, 64.3, 59.3, 54.5, 28.4, 18.1, 14.7. HRMS
(DART-Orbitrap): m/z [M + H]+ calcd for C17H22NO4, 304.1543;
found, 304.1558.
(4S)-3-(2-Hydroxy-3-methylpent-4-enoyl)-4-isopropyloxazolidin-
2-one (22). Following the procedure for rearrangement of 1d, 1g
afforded 22 and its minor isomers (90% yield, 1.7:1:0.5:0.1 selectivity).
1
Major product H NMR (500 MHz, CDCl3): δ 5.75 (ddd, J = 17.1,
10.4, 8.0 Hz, 1H), 5.11−5.05 (m, 3H), 4.38−4.35 (m, 1H), 4.33−4.30
(m, 1H), 4.30−4.28 (m, 1H), 3.19 (d, J = 8.6 Hz, 1H), 2.69−2.62 (m,
1H), 2.48 (dtd, J = 14.1, 7.0, 3.6 Hz, 1H), 1.21 (d, J = 6.9 Hz, 3H), 0.93
(dd, J = 7.1, 1.6 Hz, 3H), 0.89 (dd, J = 6.9, 1.2 Hz, 3H). 13C{1H} NMR
(126 MHz, CDCl3): δ 174.3, 153.8, 137.6, 116.6, 74.4, 64.3, 59.4, 41.4,
28.3, 18.1, 17.0, 14.6. Minor product 1H NMR (500 MHz, CDCl3): δ
5.77−5.70 (m, 1H), 5.10−5.06 (m, 2H), 5.04 (ddd, J = 17.2, 1.9, 1.2
Hz, 1H), 4.52 (dt, J = 8.6, 3.4 Hz, 1H), 4.37−4.34 (m, 1H), 4.29−4.26
(m, 1H), 3.01 (d, J = 8.9 Hz, 1H), 2.78 (dtdd, J = 9.4, 8.3, 6.5, 2.6 Hz,
1H), 2.26 (heptd, J = 6.8, 3.4 Hz, 1H), 1.26 (d, J = 6.9 Hz, 3H), 0.94−
0.92 (m, 3H), 0.90−0.89 (m, 3H). 13C{1H} NMR (126 MHz, CDCl3):
δ 174.8, 153.5, 136.9, 117.1, 74.1, 64.2, 58.3, 42.0, 28.7, 18.1, 17.7, 14.9.
HRMS (DART-Orbitrap): m/z [M + H]+ calcd for C12H20NO4,
242.1387; found, 242.1399.
129.2, 127.7, 119.1, 70.3, 67.3, 55.2, 39.1, 38.3. HRMS (DART-
Orbitrap): m/z [M + H]+ calcd for C15H18NO4, 276.1230; found,
276.1243.
(S)-3-((S)-2-Hydroxy-3,3-dimethylpent-4-enoyl)-4-isopropyloxa-
zolidin-2-one (23). To a solution of 1i (0.10 mmol, 25.5 mg) in CH2Cl2
(1.0 mL) was added n-Bu2BOTf (0.15 mmol, 150 μL) as 1.0 M solution
in CH2Cl2, and the mixture was stirred at −78 °C for 5 min.
Triethylamine (0.30 mmol, 42 μL) was added. The reaction was
warmed to rt and stirred for an additional 12 h. The reaction was
quenched with saturated NH4Cl and extracted three times with
CH2Cl2. The organic extracts were dried over MgSO4 and concentrated
in vacuo. Flash chromatography (20% ethyl acetate/hexanes) afforded
23 and its minor isomer (21.3 mg, 84% yield, 10:1 selectivity). 1H NMR
(500 MHz, CDCl3): δ 5.94 (dd, J = 17.5, 10.8 Hz, 1H), 5.22 (d, J = 10.0
Hz, 1H), 5.06 (dd, J = 10.8, 1.3 Hz, 1H), 5.02 (dd, J = 17.5, 1.3 Hz, 1H),
4.33 (ddd, J = 7.1, 3.9, 2.9 Hz, 1H), 4.26−4.20 (m, 2H), 3.10 (d, J =
10.0 Hz, 1H), 2.43 (heptd, J = 7.0, 3.8 Hz, 1H), 1.15 (s, 3H), 1.08 (s,
3H), 0.93 (d, J = 7.0 Hz, 3H), 0.89 (d, J = 7.0 Hz, 3H). 13C{1H} NMR
(126 MHz, CDCl3): δ 173.7, 154.1, 143.7, 113.6, 74.7, 64.0, 59.4, 42.3,
(S)-3-((S)-2-Hydroxypent-4-enoyl)-4-isopropyloxazolidin-2-one
(2b). Following the procedure for rearrangement of 1d, 1b afforded 2b
and its minor isomer (81% yield, 3:1 selectivity). 1H NMR (500 MHz,
CDCl3): δ 5.85 (ddt, J = 17.2, 10.2, 7.1 Hz, 1H), 5.19−5.06 (m, 3H),
4.41 (dt, J = 7.7, 3.3 Hz, 1H), 4.34 (t, J = 8.6 Hz, 1H), 4.29 (dd, J = 9.1,
2.9 Hz, 1H), 3.57 (d, J = 8.0 Hz, 1H), 2.59 (dddt, J = 14.3, 7.1, 4.9, 1.3
Hz, 1H), 2.48−2.38 (m, 2H), 0.94 (d, J = 7.0 Hz, 3H), 0.90 (d, J = 6.9
Hz, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 174.0, 154.1, 133.1,
118.6, 70.4, 64.4, 59.1, 38.4, 28.4, 18.1, 14.7. HRMS (DART-Orbitrap):
m/z [M + H]+ calcd for C11H18NO4, 228.1230; found, 228.1243.
(S)-4-Benzyl-3-((2S,3R)-2-hydroxy-3-methylpent-4-enoyl)-
oxazolidin-2-one (2c). The procedure for 1d using 1c afforded 2c and
its minor isomer as a colorless oil (90% yield, 5:1 selectivity). 1H NMR
(500 MHz, CDCl3): δ 7.34 (dd, J = 8.1, 6.5 Hz, 2H), 7.32−7.27 (m,
1H), 7.24−7.20 (m, 2H), 5.89 (ddd, J = 17.5, 10.3, 7.5 Hz, 1H), 5.16−
5.06 (m, 3H), 4.64 (ddt, J = 9.6, 6.4, 3.5 Hz, 1H), 4.26−4.23 (m, 2H),
G
J. Org. Chem. XXXX, XXX, XXX−XXX