Synthesis of Nitrogen-Containing Spiro Compounds
FULL PAPER
stored under an atmosphere of nitrogen at Ϫ20 °C. 1H NMR
(CDCl3, ppm): δ ϭ 2.07 (dd, J ϭ 14.1, 7.8 Hz, 2 H, CHHCHϭ),
oil. 1H NMR (CDCl3, ppm): δ ϭ 1.44Ϫ1.54 (m, 2 H, CH2 aza-
cycle), 1.65Ϫ1.80 (m, 4 H, 2 CH2 azacycle), 2.54 (d, J ϭ 14.4 Hz,
2.31 (br. dd, 2 H, CHHCHϭ), 2.35 (br. s, 2 H, CH2CH2), 2.52 (t, 2 H, CH2CHϭ), 2.93 (d, J ϭ 14.7 Hz, 2 H, CH2CHϭ), 3.37
J ϭ 5.1 Hz, 2 H, NCH2C), 2.72 (br. dd, 2 H, CH2CH2), 3.41 (s, 2 (pseudo t, J ϭ 5.6 Hz, 2 H, CH2N), 5.68 (s, 2 H, CHϭCH),
H, CHHPh), 3.63 (br. s, 2 H, CHHPh), 4.98Ϫ5.05 (m, 4 H, CHϭ
CH2), 5.88 (br. ddt, 2 H, CHϭCH2), 7.18Ϫ7.37 (m, 10 H, C6H5).
7.32Ϫ7.39 (m, 3 H, Ph), 7.46Ϫ7.50 (m, 2 H, Ph). 13C NMR
(CDCl3, ppm): δ ϭ 19.3, 25.1 (both CH2 azacycle), 34.7 (CH2C),
13C NMR (CDCl3, ppm): δ ϭ 46.3 (2 C, CH2CHϭ), 52.8, 54.3 44.1 (2 C, CH2CHϭ), 47.7 (CH2N), 65.6 (Cspiro), 128.0 (Ph), 128.6
(both CH2CH2), 58.8 (2 C, CH2Ph), 59.4 (NCH2C), 63.4 (Cquat), (CHϭCH), 130.2 (Ph), 138.2 (Cipso), 173.9 (CϭO). FAB-MS (rel.
117.3 (2 C, CHϭCH2), 126.9, 127.2, 128.43, 128.48, 128.7, 129.3 intensity, %): m/z ϭ 242 [M ϩ H]ϩ (100), 241 [M]ϩ (28), 240 [M
(all Ph), 135.5 (2 C, CHϭCH2), 139.2, 140.5 (both Cipso). FAB-MS Ϫ H]ϩ (23), 136 [M Ϫ PhCO]ϩ (5), 105 [PhCO]ϩ (74). HRMS
(rel. intensity, %): m/z ϭ 347 [M ϩ H]ϩ (45), 346 [M]ϩ (14), 345 (FAB): calcd. for C16H20NO [M ϩ H]ϩ 242.1545, observed
[M Ϫ H]ϩ (46), 305 [M Ϫ All]ϩ (100), 304 [M Ϫ All Ϫ H]ϩ (49), 242.1550. Anal.: calcd. C 79.63, H 7.94, N 5.80; found C 79.57, H
264 [M Ϫ 2All]ϩ (77), 213 [M Ϫ All Ϫ PhCH2 Ϫ H]ϩ (25), 173 [M
Ϫ 2All Ϫ PhCH2]ϩ (28), 91 [PhCO]ϩ (85). HRMS (FAB): calcd. for
C24H31N2 ([M ϩ H]ϩ) 347.2487, observed 347.2490. Anal.: calcd.
C 83.19, H 8.73, N 8.08; found C 83.15, H 8.69, N 8.05.
7.87, N 5.80.
6-Acetyl-6-azaspiro[4.5]dec-2-ene (4c): Isolated in a 99% yield after
chromatography (hexanes/ethyl acetate, 4:1 to 3:1) as a colourless
1
oil. H NMR (CDCl3, ppm): δ ϭ 1.56Ϫ1.70 (m, 6 H, 3 CH2 aza-
2,2,5,5-Tetraallyl-1,4-bis(trifluoroacetyl)piperazine (13): Prepared as
for 3d from 13NH in a 90% yield after silica gel chromatography
cycle), 2.03 (s, 3 H, CH3CO), 2.35 (d, J ϭ 14.7 Hz, 2 H, CH2CHϭ
), 2.85 (d, J ϭ 14.7 Hz, 2 H, CH2CHϭ), 3.40 (pseudo t, Japp
ϭ
1
5.4 Hz, 2 H, CH2N), 5.59 (s, 2 H, CHϭCH). 13C NMR (CDCl3,
ppm): δ ϭ 17.8, 24.0 (both CH2 azacycle), 24.5 (CH3), 34.6
(CH2C), 44.4 (3 C, CH2N & 2 CH2CHϭ), 65.1 (Cspiro), 128.6
(CHϭCH), 171.4 (CϭO). FAB-MS (rel. intensity, %): m/z ϭ 180
[M]ϩ (100), 179 [M Ϫ H]ϩ (24), 178 [M Ϫ 2H]ϩ (25), 136 [M Ϫ
COCH3]ϩ (20), 120 (12). HRMS (FAB): calcd. for C11H18NO [M
ϩ H]ϩ 180.1388, observed 180.1383.
(hexanes/ethyl acetate, 20:1) as a colourless oil. H NMR (CDCl3,
ppm): δ ϭ 2.48 (br. dd, 4 H, J ϭ 12.3, 6.8 Hz, CH2CHϭ), 3.03
(dd, J ϭ 14.1, 7.2 Hz, 4 H, CH2CHϭ), 3.57 (s, 4 H, NCH2), 5.17
(d, J ϭ 7.5 Hz, 4 H, CHϭCHH), 5.22 (s, 4 H, CHϭCHH), 5.63
(ddt, J ϭ 16.2, 10.8, 7.5 Hz, 4 H, CHϭCH2). 13C NMR (CDCl3,
4
ppm): δ ϭ 37.5 (4 C, CH2CHϭ), 48.2 (q, JC,F ϭ 3.6 Hz, 2 C,
2
CH2N), 63.6 (2 C, Cquat), 116.1 (q, JC,F ϭ 288.9 Hz, 2 C, CF3),
3
121.4 (4 C, CHϭCH2), 131.0 (4 C, CHϭCH2), 157.2 (q, JC,F
ϭ
35.4 Hz, 2 C, CϭO). 19F NMR (CDCl3, ppm): δ ϭ Ϫ68.8. FAB-
MS (rel. intensity, %): m/z ϭ 439 [M ϩ H]ϩ (100), 437 [M Ϫ H]ϩ
(18), 397 [M Ϫ All]ϩ (44), 301 [M Ϫ All Ϫ COCF3 ϩ H]ϩ (7), 259
[M Ϫ 2All Ϫ COCF3]ϩ (9), 204 (9), 136 (13), 107 (43), 91 (30), 79
(55), 41 (37). HRMS (FAB): calcd. for C20H25F6N2O2 [M ϩ H]ϩ
439.1820, observed 439.1807. Anal.: calcd. C 54.79, H 5.52, N 6.39;
found C 55.00, H 5.63, N 6.15.
6-(Trifluoroacetyl)-6-azaspiro[4.5]dec-2-ene (4d): Obtained as
a
colourless oil, in a 95% yield after chromatography (hexanes/ethyl
1
acetate, 12:1). H NMR (CDCl3, ppm): δ ϭ 1.65Ϫ1.80 (m, 6 H, 3
CH2 azacycle), 2.43 (d, J ϭ 14.4 Hz, 2 H, CH2CHϭ), 2.85 (d, J ϭ
14.7 Hz, 2 H, CH2CHϭ), 3.54 (pseudo t, Japp ϭ 5.4 Hz, 2 H,
CH2N), 5.63 (s, 2 H, CHϭCH). 13C NMR (CDCl3, ppm): δ ϭ
4
17.1, 23.8 (both CH2 azacycle), 33.9 (CH2C), 43.0 (q, JC,F
ϭ
2
3.6 Hz, CH2N), 43.5 (CH2CHϭ), 66.9 (Cspiro), 116.8 (q, JC,F
ϭ
General RCM Procedure: Catalyst 1a (4.1 mg, 5.00 µmol) was dis-
solved in CH2Cl2 (1 mL) in a small Schlenk tube at 22 °C. The
diene under investigation (500 µmol, 100 equiv.) was added to the
solution by syringe. The progress of the reaction was checked by
GC analysis of small aliquots of the reaction mixture. Once the
reaction was completed (4Ϫ6 h), DMSO (0.10 mL) was added to
the reaction mixture[18] and stirring continued for 18 h in order
to facilitate the removal of the catalyst decomposition products.
Purification by silica gel chromatography gave the desired product.
In experiments performed with 5 mol % of the catalyst, 100.0 µmol
of diene was used while keeping the amount of catalyst and solvent
at the same level; the progress of the reaction was monitored by
GC, but the products were not isolated.
3
289.3 Hz, CF3), 128.3 (CHϭCH), 156.8 (q, JC,F ϭ 34.6 Hz, Cϭ
O). 19F NMR (CDCl3, ppm): δ ϭ Ϫ69.8. FAB-MS (rel. intensity,
%): m/z ϭ 234 [M ϩ H]ϩ (100), 232 [M Ϫ H]ϩ (63), 95 (43), 83
(30), 81 (52), 69 [CF3]ϩ (62), 57 (75), 55 (84), 43 (49), 41 (48).
HRMS (FAB): calcd. for C11H15F3NO [M ϩ H]ϩ 234.1106, ob-
served 234.1104.
6-tert-Butoxycarbonyl-6-azaspiro[4.5]dec-2-ene (4e): Isolated after
silica gel column chromatography (eluent hexanes/ethyl acetate,
1
10:1) in a 98% yield as a colourless oil. H NMR (CDCl3, ppm):
δ ϭ 1.43 [s, 9 H, C(CH3)3], 1.45Ϫ1.65 (m, 6 H, 3 CH2 azacycle),
2.37 (d, J ϭ 14.1 Hz, 2 H, CH2CHϭ), 2.82 (d, J ϭ 14.7 Hz, 2 H,
CH2CHϭ), 3.45 (pseudo t, J ϭ 5.7 Hz, 2 H, CH2N), 5.61 (s, 2 H,
CHϭCH). 13C NMR (CDCl3, ppm): δ ϭ 18.4, 23.7 (both CH2
azacycle), 28.7 (3 C, CH3), 35.4 (CH2C), 43.1 (CH2N), 45.2 (2 C,
CH2CHϭ), 64.2 (Cspiro), 79.5 (C-O), 128.6 (CHϭCH), 156.3 (Cϭ
O). FAB-MS (rel. intensity, %): m/z ϭ 238 [M ϩ H]ϩ (26), 237
[M]ϩ (10), 182 [M Ϫ C(CH3)3 ϩ 2H]ϩ (100), 181 [M Ϫ C(CH3)3
ϩ H]ϩ (31), 180 [M Ϫ C(CH3)3]ϩ (19), 136 [M Ϫ Boc]ϩ (13), 120
(10), 57 [C(CH3)3]ϩ (26). HRMS (FAB): calcd. for C14H24NO2 [M
ϩ H]ϩ 238.1807, observed 238.1806.
6-Benzyl-6-azaspiro[4.5]dec-2-ene (4a): Isolated as a yellow oil, in a
79% yield after silica gel chromatography [petroleum ether (40Ϫ60
°C)/ethyl acetate, 15:1]. 1H NMR (CDCl3, ppm): δ ϭ 1.45Ϫ1.55
(m, 4 H, 2 CH2 azacycle), 1.71 (pseudo t, 2 H, CH2C), 2.21 (d, J ϭ
15.3 Hz, 2 H, CH2CHϭ), 2.37 (pseudo t, 2 H, CH2N), 2.62 (d, J ϭ
15 Hz, 2 H, CH2CHϭ), 3.33 (s, 2 H, CH2Ph), 5.69 (s, 2 H, CHϭ
CH), 7.18Ϫ7.39 (m, 5 H, Ph). 13C NMR (CDCl3, ppm): δ ϭ 22.2,
26.5 (both CH2 azacycle), 40.8 (2 C, CH2CHϭ), 48.5 (CH2N), 54.8
(CH2Ph), 65.4 (Cspiro), 126.6 (Ph), 128.3 (2 C, CHϭCH), 128.6
(Ph), 129.6 (Ph), 141.4 (Cipso). FAB-MS (rel. intensity, %): m/z ϭ
228 [M ϩ H]ϩ (64), 227 [M]ϩ (60), 226 [M Ϫ H]ϩ (100), 198 (20),
186 (11), 150 [M Ϫ Ph]ϩ (12), 122 (15), 91 [PhCH2]ϩ (78), 55 (15).
HRMS (FAB): calcd. for C16H22N [M ϩ H]ϩ 228.1752, observed
228.1734.
1-(Trifluoroacetyl)-1-azaspiro[4.4]non-7-ene (8): Obtained as
a
colourless oil in a 91% yield after chromatography (hexanes/ethyl
1
acetate, 12:1). H NMR (CDCl3, ppm): δ ϭ 1.89Ϫ2.00 (m, 4 H, 2
CH2 azacycle), 2.16 (d, J ϭ 14.4 Hz, 2 H, CH2CHϭ), 3.12 (d, J ϭ
14.4 Hz, 2 H, CH2CHϭ), 3.68 (tt, J ϭ 6.2, 1.2 Hz, 2 H, CH2N),
5.66 (s, 2 H, CHϭCH). 13C NMR (CDCl3, ppm): δ ϭ 24.0
6-Benzoyl-6-azaspiro[4.5]dec-2-ene (4b): Isolated in a 90% yield
(CH2CH2CH2), 42.5 (CH2C), 43.7 (2 C, CH2CHϭ), 48.4 (q,
2
after chromatography (hexanes/ethyl acetate, 12:1) as a colourless 4JC,F ϭ 4.1 Hz, CH2N), 72.0 (Cspiro), 116.5 (q, JC,F ϭ 288.5 Hz,
Eur. J. Org. Chem. 2004, 812Ϫ819
2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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