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(ddd, J = 12.6, 8.5, 4.2 Hz, 1 H, 3a-H), 1.43 (s, 3 H, Me), 1.38 (s, 3 H,
Me), 1.34 (s, 3 H, Me), 1.30 (s, 3 H, Me) ppm. 13C NMR (150 MHz,
CDCl3): δ = 119.3 (CN), 113.0 (CMe2), 109.5 (CMe2), 86.5 (C-5), 82.4
(C-4), 76.3 (C-4′), 70.8 (C-6), 68.5 (C-3a), 66.3 (C-5′), 64.2 (C-2), 36.1
(C-3), 26.5 (Me), 26.0 (Me), 25.6 (Me), 24.1 (Me) ppm. HRMS (ESI):
flask, followed by toluene (7 mL) and allyl benzoate (5; 440 mg,
2.7 mmol), which was prepared according to ref.[15] The flask was
sealed, and the mixture was stirred at 80 °C for 48 h. After this time,
TLC showed that the reaction was complete (hexanes/EtOAc, 3:7).
The mixture was concentrated to dryness, and the residue was puri-
calcd. for C15H23N2O5 [M + H]+ 311.1607; found 311.1601. Data for fied by FCC (hexanes/EtOAc, 7:3) to give two single isoxazolidines
(2R,3aS)-20d: Colourless solid. Rf = 0.55 (cyclohexane/EtOAc, 3:7). (2S,3aS)-21a (280 mg, 0.67 mmol, 49 %) and (2R,3aR)-21b (95 mg,
M.p. 107–108 °C. [α]2D5 = +85.04 (c = 0.87, CHCl3). IR (ATR): ν = 2983, 0.23 mmol, 17 %), along with a mixture of 21a and 21b (90 mg,
˜
2937, 1371, 1251, 1207, 1158, 1052, 989, 878, 844 cm–1
.
1H NMR
0.21 mmol, 15 %). Data for (2S,3aS)-21a: Colourless solid. Rf = 0.58
(600 MHz, CDCl3): δ = 4.79 (dd, J = 6.3, 1.9 Hz, 1 H, 5-H), 4.71
(pseudo t, J = 5.8 Hz, 1 H, 4-H), 4.62 (dd, J = 9.2, 6.8 Hz, 1 H, 2-H),
(cyclohexane/EtOAc, 3:7). M.p. 97–98 °C. [α]2D5 = +118.37 (c = 1.00,
CHCl3). IR (ATR): ν = 2981, 2934, 1710, 1452, 1370, 1259, 1210, 1068,
˜
4.22 (td, J = 7.0, 4.0 Hz, 1 H, 4′-H), 4.05 (dd, J = 8.0, 6.7 Hz, 1 H, 1024, 847, 714 cm–1
.
1H NMR (600 MHz, CDCl3): δ = 8.04 (d, J =
5′a-H), 3.97 (dd, J = 7.9, 7.5 Hz, 1 H, 5′b-H), 3.88 (ddd, J = 8.5, 5.2,
7.8 Hz, 2 H, Ph-H), 7.57 (t, J = 7.5 Hz, 1 H, Ph-H), 7.45 (t, J = 7.8 Hz,
3.0 Hz, 1 H, 3a-H), 3.77 (dd, J = 3.7, 1.8 Hz, 1 H, 6-H), 2.96 (ddd, J = 1 H, Ph-H), 4.96 (pseudo t, J = 6.5 Hz, 1 H, 5-H), 4.60 (dd, J = 6.7,
12.5, 6.8, 3.0 Hz, 1 H, 3a-H), 2.76 (dt, J = 12.5, 9.0 Hz, 1 H, 3b-H), 1.61
3.9 Hz, 1 H, 4-H), 4.46–4.39 (m, 2 H, 4′-H, 2-H), 4.35 (dd, J = 11.2,
7.7 Hz, 1 H, CH2OBz), 4.19 (dd, J = 11.3, 3.9 Hz, 1 H, CH2OBz), 4.12
(s, 3 H, Me), 1.39 (s, 3 H, Me), 1.33 (s, 6 H, 2 Me) ppm. 13C NMR
(150 MHz, CDCl3): δ = 117.4 (CN), 113.7 (CMe2), 109.6 (CMe2), 85.3 (dd, J = 8.6, 6.0 Hz, 1 H, 5′a-H), 4.01 (dd, J = 8.6, 5.7 Hz, 1 H, 5′b-H),
(C-5), 81.5 (C-4), 75.9 (C-4′), 71.4 (C-6), 68.8 (C-3a), 66.3 (C-5′), 63.8
3.74 (dd, J = 7.2, 3.7 Hz, 1 H, 3a-H), 3.30 (dd, J = 8.4, 6.5 Hz, 1 H, 6-
(C-2), 35.2 (C-3), 26.4 (Me), 26.1 (Me), 25.1 (Me), 24.2 (Me) ppm.
H), 2.54 (dd, J = 12.9, 8.2 Hz, 1 H, 3b-H), 2.33 (ddd, J = 12.9, 7.5,
HRMS (ESI): calcd. for C15H23N2O5 [M + H]+ 311.1607; found 5.3 Hz, 1 H, 3a-H), 1.53 (s, 3 H, Me), 1.47 (s, 3 H, Me), 1.37 (s, 3 H,
311.1600.
Me), 1.34 (s, 3 H, Me) ppm. 13C NMR (150 MHz, CDCl3): δ = 166.4
(C=O), 133.2 (CH-Ph), 130.1 (C-Ph), 129.8 (CH-Ph), 128.5 (CH-Ph),
115.1 (CMe2), 109.8 (CMe2), 88.6 (C-4), 85.6 (C-5), 75.6 (C-4′), 75.0 (C-
2), 74.8 (C-6), 71.1 (C-3a), 68.1 (C-5′), 65.7 (CH2OBz), 36.3 (C-3), 27.4
(Me), 27.0 (Me), 25.7 (Me), 24.9 (Me) ppm. HRMS (ESI): calcd. for
(4S,5R,6R)-6-[(S)-2,2-Dimethyl-1,3-dioxolan-4-yl]-4,5-isopropyl-
idenedioxyhexahydropyrrolo[1,2-b]isoxazol-2-yl Acetate (17):
Nitrone 4 (500 mg, 1.94 mmol) was placed into a reaction flask,
followed by vinyl acetate (2; 10 mL). The flask was sealed, and the
mixture was stirred at 75 °C for 24 h, after which time TLC showed
that the reaction was complete (hexanes/EtOAc, 3:7). The solvent
was then evaporated in vacuo, and the residue was purified by FCC
(hexanes/EtOAc, 6:4) to give two single isoxazolidines (2S,3aS)-17a
(320 mg, 0.93 mmol, 48 %) and (2R,3aR)-17b (90 mg, 0.26 mmol,
13 %), along with a mixture of 17a and 17b (180 mg, 0.52 mmol,
27 %). Data for (2S,3aS)-17a: Colourless syrup. Rf = 0.53 (cyclohex-
C
22H30NO7 [M + H]+ 420.2022; found 420.2014. Data for (2R,3aR)-
21b: Colourless syrup. Rf = 0.52 (cyclohexane/EtOAc, 3:7). [α]D25
–40.62 (c = 1.05, CHCl3). IR (ATR): ν = 2985, 2935, 1717, 1452, 1371,
=
˜
1269, 1206, 1068, 1026, 850, 711 cm–1 1H NMR (600 MHz, CDCl3):
.
δ = 8.07–8.04 (m, 2 H, Ph-H), 7.58–7.41 (m, 3 H, Ph-H), 4.78 (dd, J =
6.4, 2.8 Hz, 1 H, 5-H), 4.67 (pseudo t, J = 6.2, 5.9 Hz, 1 H, 4-H), 4.55–
4.51 (m, 1 H, 2-H), 4.37–4.34 (m, 2 H, CH2OBz), 4.20 (dd, J = 11.8,
6.4 Hz, 1 H, 4′-H), 4.12 (dd, J = 8.5, 6.8 Hz, 1 H, 5′a-H), 3.91 (dd, J =
8.5, 6.3 Hz, 1 H, 5′b-H), 3.86 (ddd, J = 8.6, 5.6, 3.3 Hz, 1 H, 3a-H),
3.48 (dd, J = 5.0, 2.8 Hz, 1 H, 6-H), 2.74 (ddd, J = 12.4, 8.1, 3.3 Hz, 1
H, 3b-H), 2.16 (ddd, J = 12.6, 8.6, 6.1 Hz, 1 H, 3a-H), 1.52 (s, 3 H, Me),
1.44 (s, 3 H, Me), 1.34 (s, 3 H, Me), 1.33 (s, 3 H, Me) ppm. 13C NMR
(150 MHz, CDCl3): δ = 166.4 (C=O), 133.0 (CH-Ph), 130.0 (C-Ph), 129.7
(CH-Ph), 128.3 (CH-Ph), 113.0 (CMe2), 109.6 (CMe2), 82.6 (C-5), 81.0
(C-4), 75.8 (H-4′), 75.2 (C-2), 72.4 (H-6), 67.6 (C-3a), 67.2 (C-5′), 65.8
(CH2OBz), 32.7 (C-3), 26.6 (Me), 26.5 (Me), 24.9 (Me), 24.4 (Me) ppm.
HRMS (ESI): calcd. for C22H30NO7 [M + H]+ 420.2022; found 420.2015.
ane/EtOAc, 3:7). [α]2D5 = +159.96 (c = 1.00, CHCl3). IR (ATR): ν = 2985,
˜
2937, 1741, 1371, 1227, 1208, 1064, 1009, 972, 842 cm–1
.
1H NMR
(300 MHz, CDCl3): δ = 6.32–6.26 (m, 1 H, 2-H), 4.96 (pseudo t, J =
6.5 Hz, 1 H, 5-H), 4.56 (dd, J = 6.8, 3.7 Hz, 1 H, 4-H), 4.46 (dt, J = 8.5,
5.7 Hz, 1 H, 4′-H), 4.13 (dd, J = 8.5, 5.9 Hz, 1 H, 5′a-H), 4.01 (dd, J =
8.5, 5.6 Hz, 1 H, 5′b-H), 3.88–3.79 (m, 1 H, 3a-H), 3.38–3.30 (m, 1 H,
6-H), 2.79 (ddd, J = 14.1, 6.4, 1.7 Hz, 1 H, 3b-H), 2.65 (ddd, J = 14.1,
7.7, 2.5 Hz, 1 H, 3a-H), 2.07 (s, 3 H, COMe), 1.53 (s, 3 H, Me), 1.47 (s,
3 H, Me), 1.38 (s, 3 H, Me), 1.33 (s, 3 H, Me) ppm. 13C NMR (75 MHz,
CDCl3): δ = 170.4 (C=O), 115.0 (CMe2), 109.8 (CMe2), 94.8 (C-2), 88.3
(C-5), 85.0 (C-4), 75.1 (C-4′), 75.0 (C-6), 70.5 (C-3a), 67.9 (C-5′), 41.2
(C-3), 27.2 (Me), 26.9 (Me), 25.6 (Me), 24.8 (Me), 21.2 (COMe) ppm.
HRMS (ESI): calcd. for C16H26NO7 [M + H]+ 344.1709; found 344.1701.
Data for (2R,3aR)-17b: Colourless syrup. Rf = 0.47 (cyclohexane/
Methyl (4S,5R,6R)-6-[(S)-2,2-Dimethyl-1,3-dioxolan-4-yl]-4,5-iso-
propylidenedioxyhexahydropyrrolo[1,2-b]isoxazole-2-carboxyl-
ate (22): Nitrone 4 (200 mg, 0.78 mmol) was placed into a reaction
flask, followed by toluene (8 mL) and methyl acrylate (6; 0.35 mL,
3.9 mmol). The flask was sealed, and the mixture was stirred at
80 °C for 24 h, after which time TLC showed that the reaction was
complete (hexanes/EtOAc, 3:7). The mixture was then concentrated
in vacuo, and the residue was purified by FCC (hexanes/EtOAc, 6:4)
to give one single isoxazolidine (2S,3aS)-22a (175 mg, 0.51 mmol,
65 %), along with an inseparable mixture of (2R,3aR)-22b and an
unidentified isomer (85 mg, 0.24 mmol, 31 %). Data for (2S,3aS)-
22a: Colourless solid. Rf = 0.52 (cyclohexane/EtOAc, 3:7). M.p. 74–
EtOAc, 3:7). [α]2D5 = –104.43 (c = 1.05, CHCl3). IR (ATR): ν = 2985,
˜
2937, 1740, 1372, 1233, 1206, 1070, 1056, 979, 857 cm–1
.
1H NMR
(300 MHz, CDCl3): δ = 6.27 (dd, J = 6.5, 2.3 Hz, 1 H, 2-H), 4.85 (dd,
J = 6.4, 1.0 Hz, 1 H, 5-H), 4.62 (pseudo t, J = 6.0, 5.7 Hz, 1 H, 4-H),
4.28 (td, J = 6.7, 3.8 Hz, 1 H, 4′-H), 4.14 (dd, J = 8.6, 7.2 Hz, 1 H, 5′
a-H), 3.97–3.90 (m, 1 H, 3a-H), 3.86 (dd, J = 8.5, 6.3 Hz, 1 H, 5′b-H),
3.77 (d, J = 3.4 Hz, 1 H, 6-H), 3.03 (ddd, J = 13.6, 6.5, 1.9 Hz, 1 H,
3b-H), 2.48 (ddd, J = 13.6, 8.0, 2.4 Hz, 1 H, 3a-H), 2.08 (s, 3 H, COMe),
1.48 (s, 3 H, Me), 1.42 (s, 3 H, Me), 1.31 (s, 3 H, Me), 1.30 (s, 3 H, Me)
ppm. 13C NMR (75 MHz, CDCl3): δ = 170.6 (C=O), 112.9 (CMe2), 109.8
(CMe2), 96.3 (C-2), 83.4 (C-5), 82.5 (C-4), 75.1 (C-4′), 73.1 (C-6), 68.4
(C-3a), 67.1 (C-5′), 37.5 (C-3), 26.5 (Me), 26.4 (Me), 24.5 (Me), 24.1
(Me), 21.4 (COMe) ppm. HRMS (ESI): calcd. for C16H26NO7 [M + H]+
344.1709; found 344.1705.
75 °C. [α]2D5 = +104.45 (c = 0.98, CHCl3). IR (ATR): ν = 2989, 2936,
˜
1749, 1733, 1373, 1202, 1157, 1060, 1027, 855 cm–1
.
1H NMR
(600 MHz, CDCl3): δ = 4.97 (pseudo t, J = 6.4 Hz, 1 H, 5-H), 4.60 (dd,
J = 6.5, 4.1 Hz, 1 H, 4-H), 4.52 (dd, J = 9.2, 4.2 Hz, 1 H, 2-H), 4.51–
4.46 (m, 1 H, 4′-H), 4.24 (dd, J = 8.6, 5.9 Hz, 1 H, 5′a-H), 4.04 (dd, J =
8.2, 6.3 Hz, 1 H, 5′b-H), 3.75–3.72 (m, 4 H, CO2Me, 3a-H), 3.31 (dd,
J = 8.6, 6.2 Hz, 1 H, 6-H), 2.86 (ddd, J = 12.4, 7.8, 4.3 Hz, 1 H, 3a-H),
2.70–2.65 (m, 1 H, 3b-H), 1.52 (s, 3 H, Me), 1.47 (s, 3 H, Me), 1.40 (s,
3 H, Me), 1.34 (s, 3 H, Me) ppm. 13C NMR (150 MHz, CDCl3): δ =
(4S,5R,6R)-6-{[(S)-2,2-Dimethyl-1,3-dioxolan-4-yl]-4,5-isopropyl-
idenedioxyhexahydropyrrolo[1,2-b]isoxazol-2-yl}methyl Benzo-
ate (21): Nitrone 4 (350 mg, 1.36 mmol) was placed into a reaction
Eur. J. Org. Chem. 2017, 1086–1098
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© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim