PAPER
Regioselective Azidolysis of Vinylaziridines
3207
Ethyl (E)-3-[(2R*,3R*)-1-Benzyl-3-cyclohexylaziridin-2-yl]ac-
rylate (16)
Colourless oil; yield: 282 mg (90%).
(2E,4R*,5S*)-4-Azido-5-cyclohexyl-5-hydroxypent-2-ene-
nitrile (7b)
Yellow oil; yield: 207 mg (94%).
IR (liquid film): 3160, 3030, 2985, 1720, 1620, 1260 cm–1.
IR (liquid film): 3300, 3050, 2910, 2220, 1480 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.36–7.2 (m, 5 H, Ph), 6.81 (dd,
J = 7.9, 15.6 Hz, 1 H, CH=CHCO), 6.05 (d, J = 15.6 Hz, 1 H,
CHCO), 4.22 (q, J = 7.2 Hz, 2 H, COCH2CH3), 3.50 (dd, J = 13.1,
34.1 Hz, 2 H, CH2Ph), 2.16 (dd, J = 7.9, 7.9 Hz, 1 H, CHCH=CH),
1.80–0.96 (m, 15 H, Cy-CH + Cy + COCH2CH3).
1H NMR (300 MHz, CDCl3): δ = 6.78 (dd, J = 6.8, 16.4 Hz, 1 H,
CH=CHCN), 5.67 (dd, J = 1.3, 16.4 Hz, 1 H, CHCN), 4.14 (ddd,
J = 1.3, 4.7, 6.8 Hz, 1 H, CHN3), 3.45 (dd, J = 4.7, 7.0 Hz, 1 H,
CHOH), 2.29 (br s, 1 H, OH), 1.96–0.90 (m, 11 H, Cy).
13C NMR (75 MHz, CDCl3): δ = 148.3, 116.6, 103.5, 76.8, 64.7,
39.9, 29.9, 27.9, 26.2, 25.9, 25.7.
13C NMR (75 MHz, CDCl3): δ = 166.2, 146.1, 138.7, 128.4, 127.2,
123.2, 65.3, 60.3, 53.3, 44.3, 37.5, 31.2, 30.0, 26.0, 25.5, 14.0.
HRMS (ES Q-TOF): m/z [M + H]+ calcd for C20H27NO2: 314.2120;
HRMS (ES Q-TOF): m/z [M + H]+ calcd for C11H16N4O: 221.1403;
found: 221.1406.
found: 314.2124.
Ethyl (2E,4S*,5R*)-4-Azido-5-cyclohexyl-5-(ethoxycarbonyl-
amino)pent-2-enoate (20)
(E)-3-[(2R*,3R*)-1-Benzyl-3-cyclohexylaziridin-2-yl]acryloni-
trile (17)
Colourless oil; yield: 239 mg (90%).
IR (liquid film): 3150, 3020, 2985, 2200, 910 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.4–7.23 (m, 5 H, Ph), 5.97 (dd,
J = 7.7, 16.1 Hz, 1 H, CH=CHCN), 5.65 (d, J = 16.1 Hz, 1 H,
CHCN), 3.86–3.47 (m, 2 H, CH2Ph), 2.53 (dd, J = 2.5, 7.7 Hz, 1 H,
CHCH=CH), 2.00–0.80 (m, 12 H, Cy-CH + Cy).
13C NMR (75 MHz, CDCl3): δ = 151.1, 128.7, 128.4, 128.2, 127.5,
117.1, 101.6, 58.3, 55.3, 43.3, 41.5, 30.8, 30.0, 26.0, 25.7, 25.5.
Yellow oil; yield: 321 mg (95%).
IR (liquid film): 2985, 2095, 1725, 1320, 980 cm–1.
1H NMR (300 MHz, CDCl3): δ = 6.80 (dd, J = 6.7, 15.8 Hz, 1 H,
CH=CHCO), 6.07 (dd, J = 15.8, 15.8 Hz, 1 H, CHCO), 4.59 (d,
J = 10.2 Hz, 1 H, NH), 4.31 (dd, J = 2.7, 6.7 Hz, 1 H, CHN3), 4.20
(q, J = 7.2 Hz, 4 H, 2 × COCH2CH3), 3.53 (ddd, J = 2.7, 10.2, 10.7
Hz, 1 H, CHNH), 1.83–1.55 (m, 5 H, Cy), 1.30–0.90 (m, 12 H,
Cy + 2 × CH3).
13C NMR (75 MHz, CDCl3): δ = 171.2, 165.4, 142.1, 124.5, 63.4,
61.1, 60.8, 57.8, 39.9, 30.1, 29.0, 26.1, 25.9, 25.8, 14.5, 14.2.
HRMS (ES Q-TOF): m/z [M + H]+ calcd for C16H26N4O4:
HRMS (ES Q-TOF): m/z [M + H]+ calcd for C18H22N2: 267.1862;
found: 267.1860.
339.2032; found: 339.2030.
Ethyl(E)-3-[(2R*,3R*)-3-Propyl-1-p-tosylaziridin-2-yl]acrylate
(18)
Ethyl (2E,4S*,5R*)-4-Azido-5-[(9-fluorenylmethoxycarbon-
yl)amino]oct-2-enoate (21)
Pale yellow oil; yield: 428 mg (96%).
IR (liquid film): 2965, 2090, 1730, 1530, 1230 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.76–7.30 (m, 8 H, HArFmoc), 6.82
(dd, J = 6.1, 15.5 Hz, 1 H, CH=CHCO), 6.07 (dd, J = 15.5, 15.5 Hz,
1 H, CHCO), 4.78 (d, J = 9.0 Hz, 1 H, NHFmoc), 4.65 (dd, J = 6.5,
10.8 Hz, 1 H, CHaHbFmoc), 4.40 (dd, J = 6.5, 10.8 Hz, 1 H,
CHaHbFmoc), 4.30–4.10 (m, 4 H, CHN3 + CHFmoc + COCH2CH3),
Aziridine 8a (184 mg, 1 mmol) was dissolved in anhyd pyridine
(1.5 mL). TsCl (190 mg, 1.1 mmol) was then added and the reaction
mixture was stirred at r.t. for 12 h (TLC monitoring). Then, the mix-
ture was diluted with Et2O (15 mL) and washed with sat. CuSO4
soln (20 mL). The organic layer was washed with brine (20 mL),
dried (Na2SO4) and then concentrated under reduced pressure to
leave the crude product, which was purified by flash chromatogra-
phy on silica gel (hexane–EtOAc, 9:1) to afford 18 as a light yellow
oil; yield: 209 mg (62%).
3.77–3.67 (m,
1
H, CHNHFmoc), 1.48–1.20 (m,
7
3
H,
H,
IR (liquid film): 2969, 1710, 1655, 1603, 1234 cm–1.
CH2CH2CH3 + COCH2CH3), 0.93 (t, J = 7.2 Hz,
CH2CH2CH3).
13C NMR (75 MHz, CDCl3): δ = 165.6, 156.5, 143.9, 143.8, 141.5,
127.9, 127.2, 125.1, 120.7, 66.9, 66.4, 60.5, 53.5, 47.5, 31.7, 19.5,
14.0, 13.9.
HRMS (ES Q-TOF): m/z [M + H]+ calcd for C25H28N4O4:
449.2188; found: 449.2185.
1H NMR (300 MHz, CDCl3): δ = 7.71 (d, J = 8.2 Hz, 2 H, HAr), 7.35
(d, J = 8.2 Hz, 2 H, HAr), 6.74 (dd, J = 6.6, 15.5 Hz, 1 H,
CH=CHCO), 6.04 (d, J = 15.5 Hz, 1 H, CHCO), 4.20 (q, J = 7.2 Hz,
2 H, COCH2CH3), 3.38 (dd, J = 2.9, 6.6 Hz, 1 H, CHCH=CH), 2.50
(m, 1 H, CH2CH), 2.46 (s, 3 H, ArCH3), 1.80–1.40 (m, 4 H,
CH2CH2CH3), 1.13 (t, J = 7.2 Hz, 3 H, COCH2CH3), 0.90 (t, J = 7.1
Hz, 3 H, CH2CH2CH3).
13C NMR (75 MHz, CDCl3): δ = 165.4, 144.6, 139.1, 134.7, 129.7,
126.6, 125.8, 60.5, 45.1, 42.7, 32.9, 21.5, 20.1, 14.4, 14.0.
HRMS (ES Q-TOF): m/z [M + H]+ calcd for C17H23NO4S:
338.1426; found: 338.1422.
(2E,4S*,5R*)-4-Azido-5-(tert-butoxycarbonylamino)-5-cyclo-
hexylpent-2-enenitrile (22)
Yellow oil; yield: 310 mg (97%).
IR (liquid film): 2975, 2215, 2095, 1720, 1312, 980 cm–1.
1H NMR (300 MHz, CDCl3): δ = 6.49 (dd, J = 10.2, 15.8 Hz, 1 H,
CH=CHCN), 5.57 (d, J = 15.8 Hz, 1 H, CHCN), 4.49 (d, J = 10.1
Hz, 1 H, NH), 4.33 (dd, J = 10.2, 9.5 Hz, 1 H, CHN3), 3.59 (ddd,
J = 10.6, 10.1, 9.5 Hz, 1 H, CHNHBoc), 1.87–1.54 (m, 6 H, Cy),
1.40 [s, 9 H, C(CH3)3], 1.35–1.07 (m, 5 H, Cy).
13C NMR (75 MHz, CDCl3): δ = 155.8, 149.1, 115.0, 103.4, 80.1,
62.9, 57.0, 37.9, 30.6, 28.4, 26.3, 26.1.
BF3·OEt2/TMSN3 Mediated Ring-Opening Reaction; General
Procedure
To a stirred soln of the appropriate protected aziridine (1 mmol) in
anhyd CH2Cl2 (3.3 mL) were added dropwise, under argon atmo-
sphere at 0 °C, TMSN3 (115 mg, 0.13 mL, 1 mmol) and BF3·OEt2
(283 mg, 0.25 mL, 2 mmol), and the reaction mixture was left stir-
ring at r.t. After complete consumption of the substrate (TLC mon-
itoring), the mixture was diluted with CH2Cl2 (10 mL) and washed
with aq NaHCO3 soln and aq NaCl soln until pH 7. The organic lay-
er was dried (Na2SO4) and concentrated under reduced pressure to
leave the crude product, which was filtered through a silica gel pad
to give the desired product.
HRMS (ES Q-TOF): m/z [M + H]+ calcd for C16H25N5O2:
320.2087; found: 320.2083.
(2E,4S*,5R*)-4-Azido-5-(ethoxycarbonylamino)oct-2-ene-
nitrile (23)
Pale yellow oil; yield: 246 mg (98%).
IR (liquid film): 2986, 2215, 2098, 1720, 1330, 980 cm–1.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 3202–3208