N-Amino-exo-3,6-epoxy-1,2,3,6-tetrahydrophthalimide in Aminoaziridinations
171–172 °C. 1H NMR (400 MHz, CDCl3): δ = 2.71 (d, J = 6.4 Hz,
1 H, Ha), 2.88 (d, J = 6.4 Hz, 1 H, HaЈ), 4.29 (d, J = 4.4 Hz, 1 H,
1-(exo-3,6-Epoxy-1,2,3,6-tetrahydrophthalimidyl)-2-nitro-3-phenyl-
aziridine (5o): Yield: 549 mg (30 %). Light-yellow crystals, m.p.
NCH), 4.48 (d, J = 4.4 Hz, 1 H, NCH), 5.24 (d, J = 1.6 Hz, 1 H, 133–134 °C (decomp.). Two invertomers ≈2:1.[4] 1H NMR
Hb), 5.26 (d, J = 1.6 Hz, 1 H, HbЈ), 6.46 (m, 1 H, Hc), 6.50 (m, 1 (400 MHz, [D6]DMSO): δ = 2.51–2.68 (br. m, 2 H, 1,2-H major),
H. HcЈ), 7.50–7.56 (m, 2 H, Hm), 7.61–7.66 (m, 3 H, HoЈ + Hp),
2.77–2.95 (br. m, 1 H, 1,2-H minor), 4.51 (br. s, 1 H), 4.68–4.74
8.04–8.09 (m, 2 H, Ho), 8.21–8.26 (m, 2 H, HmЈ) ppm. 13C NMR (br. m, 1.5 H), 5.15 (s, 1 H), 5.25–5.35 (br. m, 1 H), 5.43 (br. s, 0.5
(100 MHz, CDCl3): δ = 45.30 and 45.85 (C-1,2), 48.59 (NCH), H), 6.35–6.60 (br. m, 4 H, 4,5-H + CHNO2 major), 7.25–7.48 (br.
48.92 (NCH), 80.36 and 80.60 (C-3,6), 123.81 (p-C6H4NO2, Cm), m, 8 H, Ph + CHNO2 minor) ppm. 13C NMR (100 MHz, CDCl3):
128.05, 128.79, 128.80, 133.33 (Bz Ci), 133.91 (Bz Cp), 136.24 and
δ = 45.30, 45.72 and 46.08 (minor) (C-1,2); 49.89 (NCHPh minor),
136.43 (C-4,5), 141.45 and 142.28 (p-C6H4NO2, Ci and Cp), 171.87 51.70 (NCHPh major), 70.95 (CHNO2 major), 73.60 (CHNO2
(NC=O), 171.95 (NC=O), 189.15 (C=O) ppm. HRMS (ESI+): minor); 80.23 and 80.41 (C-3,6); 127.18, 128.65, 128.92, 129.50,
calcd. for C23H17N3O6 [M + Na]+ 454.1010; found 454.1010
(–0.4 ppm error).
130.18; 135.92, 136.39 and 136.49 (C-4,5 and Ci) ppm. HRMS
(ESI+): calcd. for C16H13N3O5 [M + H]+ 328.0928; found 328.0928
(–0.4 ppm error).
2-Benzoyl-1-(exo-3,6-epoxy-1,2,3,6-tetrahydrophthalimidyl)-3-(4-chlo-
rophenyl)aziridine (5k): Yield: 1.626 g (69%). White crystals, m.p.
7-(exo-3,6-Epoxy-1,2,3,6-tetrahydrophthalimidyl)-7-azabicy-
1
clo[4.1.0]heptan-2-one (5p): Yield: 322 mg (21%). White crystals,
179–180 °C (decomp.). H NMR (400 MHz, CDCl3): δ = 2.69 (d,
1
J = 6.4 Hz, 1 H, Ha), 2.86 (d, J = 6.4 Hz, 1 H, HaЈ), 4.25 (d, J =
4.8 Hz, 1 H, NCH), 4.38 (d, J = 4.8 Hz, 1 H, NCH), 5.22 (d, J =
1.6 Hz, 1 H, Hb), 5.26 (d, J = 1.6 Hz, 1 H, HbЈ), 6.45 (m, 1 H, Hc),
6.50 (m, 1 H, HcЈ), 7.32–7.42 (m, 4 H, p-C6H4Cl), 7.49–7.54 (m, 2
H, Hm), 7.61 (m, 1 H, Hp), 8.04–8.08 (m, 2 H, Ho) ppm. 13C NMR
(100 MHz, CDCl3): δ = 45.30 and 45.87 (C-1,2), 48.45 (NCH),
49.56 (NCH), 80.36 and 80.61 (C-3,6), 128.75, 128.77, 128.85,
133.55 (Bz, Ci or p-ClC6H4, C-Cl), 133.72 (Bz Cp), 134.48 (Bz, Ci
or p-ClC6H4, C-Cl), 136.27 and 136.46 (C-4,5), 136.99 (p-C6H4Cl,
Ci), 172.02 (NC=O), 172.05 (NC=O), 189.85 (C=O) ppm. HRMS
(ESI+): calcd. for C23H17ClN2O4 [M + H]+ 421.0950; found
421.0950 (–0.7 ppm error).
m.p. 163–164 °C. H NMR (400 MHz, CDCl3): δ = 1.62–1.71 (m,
1 H), 1.83–2.12 (m, 3 H), 2.40–2.52 (m, 2 H), 2.75 (s, 2 H, Ha),
2.87 (d, J = 7.2 Hz, H1Ј), 3.22 (dt, J = 7.2, 2.4 Hz, 1 H, H6Ј), 5.21
(m, 2 H, Hb), 6.48 (m, 2 H, Hc) ppm. 13C NMR (100 MHz,
CDCl3): δ = 17.99 (C-4Ј), 21.84 (C-5Ј), 36.87 (C-3Ј), 45.44 and
45.50 (C-1,2), 46.25 (C-6Ј), 49.09 (C-1Ј), 80.57 and 80.61 (C-3,6),
136.29 (C-4,5), 171.75 (NC=O), 202.83 (C-2Ј) ppm. HRMS (ESI+):
calcd. for C14H14N2O4 [M + H]+ 275.1032; found 275.1032 (–
0.7 ppm error).
2-Acetyl-1-(exo-3,6-epoxy-1,2,3,6-tetrahydrophthalimidyl)-3-pentyl-
aziridine (5q): Yield: 730 mg (41 %). White crystals, m.p. 124–
125 °C. 1H NMR (400 MHz, CDCl3): δ = 0.88 (m, 3 H, Me of
C5H11), 1.28–1.38 (m, 4 H), 1.48–1.58 (m, 3 H), 1.77 (m, 1 H), 2.43
(s, 3 H, COMe), 2.64 (d, J = 6.4 Hz, 1 H, Ha), 2.78 (d, J = 6.4 Hz,
1 H, HaЈ), 3.14 (m, 1 H, NCHC5H11), 3.20 (d, J = 4.8 Hz, 1 H,
NCHCOMe), 5.22 (s, 1 H, Hb), 5.25 (s, 1 H, HbЈ), 6.47 (m, 2 H,
Hc + HcЈ) ppm. 13C NMR (100 MHz, CDCl3): δ = 13.99 (Me of
C5H11), 22.45, 25.65, 26.94, 31.09, 31.50 (4CH2 and Me of Ac),
45.17 and 45.81 (C-1,2), 48.62 (NCH), 49.35 (NCH), 80.29 and
80.50 (C-3,6), 136.29 and 136.39 (C-4,5), 172.24 (NC=O), 172.62
(NC=O), 199.37 (C=O) ppm. HRMS (ESI+): calcd. for
C17H22N2O4 [M + H]+ 319.1658; found 319.1658 (–0.3 ppm error).
2-Benzoyl-1-(exo-3,6-epoxy-1,2,3,6-tetrahydrophthalimidyl)-3-(4-
methoxyphenyl)aziridine (5l): Yield: 1.726 g (74%). White crystals,
m.p. 179–180 °C. 1H NMR (400 MHz, CDCl3): δ = 2.69 (d, J =
6.4 Hz, 1 H, Ha), 2.86 (d, J = 6.4 Hz, 1 H, HaЈ), 3.81 (s, 3 H, OMe),
4.28 (d, J = 4.8 Hz, 1 H, NCH), 4.36 (d, J = 4.8 Hz, 1 H, NCH),
5.22 (d, J = 1 Hz, 1 H, Hb), 5.26 (d, J = 1 Hz, 1 H, HbЈ), 6.44 (m,
1 H, Hc), 6.49 (m, 1 H, HcЈ), 6.90 (m, 2 H, Hm), 7.38 (m, 2 H, Ho),
7.51 (m, 2 H, H2 Bz), 7.61 (m, 1 H, H3 Bz), 8.05 (m, 2 H, H1 Bz)
ppm. 13C NMR (100 MHz, CDCl3): δ = 45.27 and 45.86 (C-1,2),
48.43 (NCH), 50.24 (NCH), 55.35 (MeO), 80.34 and 80.58 (C-3,6),
114.11 (Cm), 126.97 (p-Anys, Ci), 128.32, 128.69, 128.71, 133.55
(2Z)-4-[(exo-3,6-Epoxy-1,2,3,6-tetrahydrophthalimidyl)imino]but-2-
(Bz, Cp), 136.25 and 136.46 (C-4,5), 137.19 (Bz, Ci), 159.87 (C- enal (6): Yield: 551 mg (40%). Yellow crystals, decomposes below
OMe), 172.05 (NC=O), 172.14 (NC=O), 190.30 (C=O) ppm.
HRMS (ESI+): calcd. for C24H20N2O5 [M + H]+ 417.1445; found
417.1445 (–0.3 ppm error).
1
120 °C. H NMR (400 MHz, CDCl3): δ = 2.92 (s, 2 H, Ha), 5.36
(s, 2 H, Hb), 6.44 (ddd, J = 11.6, 6.8, 1.2 Hz, 1 H, H1), 6.55 (s, 2
H, Hc), 7.09 (dd, J = 11.6, 10.0 Hz, 1 H, H2), 10.07 (dd, J = 10.0,
1.2 Hz, 1 H, Him), 10.22 (d, J = 6.8 Hz, 1 H, Hal) ppm. 13C NMR
(100 MHz, CDCl3): δ = 45.49 (C-1,2), 81.29 (C-3,6), 135.83 (=CH),
136.54 (C-4,5), 140.97 (=CH), 154.11 (C=N), 172.55 (NC=O),
189.56 (CH=O) ppm. HRMS (ESI+): calcd. for C12H10N2O4 [M +
H]+ 247.0719; found 247.0719 (–0.4 ppm error).
7-(exo-3,6-Epoxy-1,2,3,6-tetrahydrophthalimidyl)-7-azabicyclo[4.1.0]-
heptane (5m): Yield: 364 mg (25 %). White crystals, m.p. 170–
171 °C. 1H NMR (400 MHz, CDCl3): δ = 1.18–1.29 (m, 2 H), 1.32–
1.44 (m, 2 H), 1.84–1.94 (m, 2 H), 2.12–2.22 (m, 2 H), 2.57 (m, 2
H, H1Ј), 2.70 (s, 2 H, Ha), 5.20 (s, 2 H, Hb), 6.47 (s, 2 H, Hc) ppm.
13C NMR (100 MHz, CDCl3): δ = 19.91 (C3Ј), 23.02 (C2Ј), 43.97
and 45.53 (C1Ј and C-1,2), 80.51 (C-3,6), 136.30 (C-4,5), 172.51
(NCO) ppm. HRMS (ESI+): calcd. for C14H16N2O3 [M + H]+
261.1234; found 261.1234 (+0.1 ppm error).
Study of Competitive Oxidative Addition of EPTN-NH2 to Dimethyl
Fumarate (4e) vs. Maleate (4f) in CDCl3: Anhydrous K2CO3(2.30 g,
16.7 mmol), PhI(OAc)2 (1.79 g, 5.6 mmol), 2(1.00 g, 5.6 mmol), di-
methyl maleate (2.33 g, 16.2 mmol), and dimethyl fumarate (2.34 g,
16.3 mmol) were mixed in CDCl3 (30 mL). The mixture was stirred
at room temperature and 10 NMR spectra of 10 0.5-mL aliquots
were taken within 270 min. Reaction was complete in 4 h. Isolation
of the product was carried out as described above. Yield of trans-
aziridine 5e was 42 %.
1-(exo-3,6-Epoxy-1,2,3,6-tetrahydrophthalimidyl)-1a,7a-dihydro-
1H-naphtho[2,3-b]azirene-2,7-dione (5n): Yield: 395 mg (21%). Yel-
low crystals, m.p. 179–180 °C. 1H NMR (400 MHz, [D6]DMSO): δ
= 2.87 (s, 2 H, Ha), 3.91 (s, 2 H, Haz), 5.12 (s, 2 H, Hb), 6.53 (s, 2
H, Hc), 7.85–7.96 (m, 4 H, o-C6H4) ppm. 13C NMR (100 MHz,
[D6]DMSO): δ = 45.26 (C-1,2), 48.76 (NCH), 80.23 (C-3,6), 126.35
(C-3,6, Ar), 132.64 (C-2a,6a, Ar), 134.70 (C-4,5, Ar), 136.28 (C-
4,5), 171.83 (NC=O), 188.38 (C=O) ppm. HRMS (ESI+): calcd.
Supporting Information (see also the footnote on the first page of
this article): Copies of NMR spectra of all compounds and crystal-
lographic data for compounds 5c and 5f.
for C18H12N2O5 [M + H]+ 337.0819; found 337.0819 (–0.3 ppm CCDC-733493 (for 5c) and -733494 (for 5f) contain the supplemen-
error).
tary crystallographic data for this paper. These data can be ob-
Eur. J. Org. Chem. 2009, 3635–3642
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3641