M. Gulla et al. · Bromocyclization of Unsaturated Oximes
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13C NMR (125.7 MHz, CDCl3): δ = 24.1, 24.7, 25.1, 29.6, trone 21a (260 mg, 30%) as a pale-yellow oil and the spiro-
34.70, 34.74 (t each, C-3, C-5, C-6, C-7, C-8, C-1’), 41.5 (d, lactone 22 (305 mg, 39%) as colorless solid crystals suit-
C-4), 72.6 (d, C-2), 150.4 (s, C-9). – C9H14BrNO (232.1): able for structure analysis [1d]. – Nitrone 21a: IR (film):
calcd. C 46.56, H 6.08, N 6.03, Br 34.42; found for 19 (exo) ν = 1721, 1637, 1187 cm−1. – 1H NMR (300.1 MHz,
C 46.26, H 6.11, N 5.95, Br 34.22.
CDCl3): δ = 1.28 (t, J = 7.1 Hz, 3 H, OCH2CH3), 1.5 –
2.51 (m, 6 H, 3 CH2), 2.64 – 2.76 (m) and 2.7 – 2.8 (dd,
J2,3 = 6.6, J3A,3B = 13.2 Hz, 1 H, together 2 H, 3-HA,
Ethyl 1-allyl-2-oximinocyclopentanonecarboxylate (20a)
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3-HB), 3.64 – 3.68 (dd, J2,1 A = 2.9, J1 A,1 B = 11 Hz, 1 H,
Prepared following Typical Procedure B: Ethyl 1-allyl-
2-cyclopentanone-1-carboxylate [40b] (3.00 g, 15.2 mmol),
ethanol (18 ml), hydroxylamine hydrochloride (2.12 g,
30.6 mmol) in water (6 ml), Na2CO3 (1.61 g, 15.2 mmol)
in water (15 ml), reflux overnight; extraction with CH2Cl2
(3×50 ml), drying (MgSO4), concentration in vacuo; crude
product [oxime 20a, 3.19 g, 99%, (E)/(Z) mixture 78 : 22
from NMR] subjected to flash chromatography (silica, col-
umn 3 cm ×30 cm, hexane/EtOAc 4 : 1) to give analyti-
cally pure oxime (E)-20a (2.46 g, 76%) and analytically pure
oxime (Z)-20a (560 mg, 17%) both as colorless solids. –
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1’-HA), 4.06 – 4.12 (dd, J2,1 B = 5.1, J1 A,1 B = 11.0 Hz, 1 H,
1’-HB), 4.17 – 4.24 (q, J = 7.1 Hz, 2 H, OCH2CH3), 4.85 –
4.86 (m, 2-H). – 13C NMR (75.5 MHz, CDCl3): δ = 14.2
(q, OCH2CH3), 22.3, 25.9, 32.7, 34.4, 36.1 (t each, C-3,
C-6, C-7, C-8, C-1’), 58.9 (s, C-4), 62.1 (t, OCH2CH3),
76.4 (d, C-2), 144.2 (s, C-5), 172.0 (s, CO2Et). – Spiro-
lactone 22: M. p. 127 – 129 ◦C. – IR (film): ν = 3319 (OH),
1736, 1202, 1017, 954, 919 cm−1. – 1H NMR (300.1 MHz,
CDCl3): δ = 1.79 – 2.69 (m, 8 H, 4 CH2), 3.50 – 3.56 (dd,
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J3,1 A = 6.14, J1 A,1 B = 10.8 Hz, 1 H, 1’-HA), 3.57 – 3.62
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(dd, J3,1 B = 4.7, J1 A,1 B = 10.8 Hz, 1 H, 1’-HB), 4.85 –
4.93 (m, 1 H, 3-H), 7.52 (sb, NOH). – 13C NMR (75.5 MHz,
CDCl3,): δ = 22.1, 26.9, 33.3, 36.1, 39.6 (t each, C-4, C-7,
C-8, C-9, C-1’), 53.5 (s, C-5), 75.8 (d, C-3), 167.3 (s, C-6),
176.6 (s, C-1).
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Major isomer (E)-20a: M. p. 70 – 71 C. – IR (film): ν =
3241 (OH), 2975, 1715, 1440, 1420, 1271, 1217, 1144,
1044, 1025, 983, 938, 915, 866, 724 cm−1. – 1H NMR
(250.1 MHz, CDCl3): δ = 1.25 (t, J = 7.1 Hz, 3 H,
OCH2CH3), 1.75 – 1.86 (m, 2 H), 2.3 – 2.47 (m, 2 H), 2.51 –
2.62 (m, 2 H), 2.76 (m, 2 H), 4.1 – 4.23 (m, 2 H, OCH2CH3),
5.05 – 5.13 (m, 2 H, 3’-H), 5.77 (dd, J = 10.2, 17.0 Hz, 1 H,
2’-H), 9.3 (sb, 1-H, OH). – 13C NMR (62.8 MHz, CDCl3):
δ = 14.1 (q, OCH2CH3), 21.5, 27.4, 34.1, 40.7 (t each, C-3,
C-4, C-5, C-1’), 55.9 (s, C-2), 61.4 (t, OCH2CH3), 118.5 (t,
C-2’), 133.7 (d, C-3’), 165.6 (s, C-1), 172.8 (s, CO2Et). – Mi-
nor isomer (Z)-20a: M. p. 38 – 39 ◦C. – IR (film): ν = 1730,
1220, 746, 666 cm−1. – 1H NMR (250.1 MHz, CDCl3):
δ = 1.23 (t, J = 7.1 Hz, 3 H, OCH2CH3), 1.78 – 2.90 (m,
8 H, 4 CH2), 4.12 – 4.21 (q, J = 7.1 Hz, 2 H, OCH2CH3),
5.07 – 5.13 (m, 2 H, 3’-H), 5.60 – 5.83 (m, 1 H, 2’-H), 8.82
(sb, 1 H, OH). – 13C NMR (62.8 MHz, CDCl3): δ = 14.1
(q, OCH2CH3), 23.3, 32.0, 36.3, 36.7 (t each, C-3, C-4,
C-5, C-1’), 54.0 (s, C-2), 60.8 (t, OCH2CH3), 118.6 (t,
C-2’), 134.3 (d, C-3’), 165.2 (s, C-1), 174.2 (s, CO2Et). –
C11H17NO3 (232.1): calcd. C 62.54, H 8.11, N 6.63, found
for (E)-20a C 62.28, H 8.08, N 6.53; found for minor isomer
(Z)-20a C 62.51, H 8.11, N 6.53.
tert-Butyl 1-allyl-2-oximino-cyclopentanecarboxylate (20b)
Following Typical Procedure B, from tert-butyl 1-allyl-
2-cyclopentanonecarboxylate [40] (2.24 g, 10.0 mmol), hy-
droxylamine hydrochloride (1.39 g, 20.0 mmol) in water
(6 ml), with Na2CO3 (1.06 g, 10.0 mmol) in water (10 ml),
reflux overnight. After the usual work-up the crude product
of 20b [2.30 g, 96%, (E)/(Z) 90 : 10 from NMR] was sub-
jected to flash chromatography (silica, column 3 cm ×30 cm,
hexane/EtOAc 4 : 1) to give analytically pure oxime (E)-20b
(1.85 g, 77%) and analytically pure oxime (Z)-20b (230 mg,
10%) both as a colorless oil. – Major isomer (E)-20b: IR
(film): ν = 3302 (OH), 1721, 1142, 983, 917, 866 cm−1. –
1H NMR (300.1 MHz, CDCl3): δ = 1.43 (s, 9 H, C(CH3)3),
1.64 – 1.91 (m, 3 H, CH2, and H of CH2), 2.04 – 2.74 (m, 5 H,
2 CH2, and H of CH2), 5.05 – 5.11 (m, 2 H, 3’-H), 5.68 – 5.82
(m, 1 H, 2’-H), 9.03 (sb, 1-H, OH). – 13C NMR (75.5 MHz,
CDCl3): δ = 21.8, 27.5 (t, C-4, C-3), 27.9 (q, C(CH3)3),
34.5, 40.5 (t, C-5, C-1’), 56.5 (s, C-2), 81.4 (s, C(CH3)3),
118.3 (t, C-3’), 134.1 (d, C-2’), 166.0 (s, C-1), 171.2 (s,
CO2CMe3). – C13H21NO3 (239.3): calcd. C 65.25, H 8.84,
N 5.84, found C 65.07, H 8.75, N 5.80. – Minor isomer
Ethyl 2-bromomethyl-2,4,5,6-tetrahydro-3H-cyclopenta[b]
pyrrole-3a-carboxylate 1-oxide (21a) and 3-bromomethyl-
6-oximino-2-oxa-spiro[4.4]nonane-1,6-dione (22)
Typical Procedure A was used: Oxime (E)-20a (633 mg, (Z)-20b: IR (film): ν = 3242 (OH), 1728, 1367, 1251, 1145,
3.0 mmol) in CH2Cl2 (16 ml, abs.), NaHCO3 (755 mg, 1059, 915, 847, 734, 649 cm−1. – 1H NMR (300.1 MHz,
9.0 mmol), addition of bro◦mine (503 mg, 3.15 mmol) in CDCl3): δ = 1.43 (s, 9 H, C(CH3)3), 1.77 – 2.0 (m, 4 H,
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CH2Cl2 (12 ml, abs.) at 0 C within 3 h and usual work- 2 CH2), 2.27 – 2.52 (m, 2 H, CH2), 2.53 (dd, J2,1 A = 8.3,
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up. The crude product was subjected to flash chromatog- J1 A,1 B = 13.8 Hz, 1 H, 1’-HA), 2.92 (dd, J2,1 B = 6.7,
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raphy (silica, column 3 cm ×30 cm, hexane/EtOAc 6 : 4 J1 A,1 B = 13.8, Hz, 1 H, 1’-HB), 5.01 – 5.08 (m, 2 H, 3’-H),
to EtOAc/MeOH 9 : 1) to afford spectroscopically pure ni- 5.72 – 5.75 (m, 1 H, 2’-H), 9.03 (sb, 1-H, OH). – 13C NMR
Unauthenticated
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