Desulfonylative Azide Transfer
A R T I C L E S
Scheme 11. Synthesis of Lepadiformine C
28.6, 25.3, 22.1, 14.2. IR (neat): 2936, 2861, 2101, 1738, 1451, 1377,
1302, 1258, 1174, 1024, 895 cm-1. MS (EI) m/z (%): 226 (8, [MH]+),
198 (37), 183 (100), 168 (7), 152 (17), 137 (21), 125 (20), 109 (14), 96
(37), 82 (10), 67 (13), 56 (20). Anal. Calcd for C11H19N3O2: C, 58.64; H,
8.50; N, 18.65. Found: C, 58.70; H, 8.47; N, 18.55.
3-Azido-1,1,1-trichlorodecane (25). Compound 25 was obtained
according to the GP from 22 (269 mg, 1.2 mmol), 1-octene (67 mg, 0.6
mmol), and di-tert-butyldiazene (43 mg, 0.3 mmol) in benzene. The crude
product was purified by flash chromatography (pentane) to afford 25 (134
mg, 82%) as a colorless liquid. 1H NMR (CDCl3, 300 MHz): δ 4.32-4.23
(m, 1H), 3.27 (dd, J ) 5.8, 15.7 Hz, 1H), 3.12 (dd, J ) 4.2, 15.7 Hz,
1H), 2.01-1.77 (m, 2H), 1.61-1.27 (m, 8H), 0.97-0.85 (m, 3H). 13
C
NMR (CDCl3, 75 MHz): δ 97.2, 60.4, 58.9, 35.7, 31.6, 28.8, 25.7, 22.5,
14.0. IR (diamond ATR): 2928, 2857, 2096, 1467, 1275, 780 cm-1. MS
(EI) m/z (%) 274 (20, [M+]), 273 (11, [M+]), 272 (0.2, [M+]), 271 (0.9,
[M+]), 255 (M+, 0.9), 199 (20), 154 (25), 126 (20), 114 (24), 112 (49),
84 (22), 71 (20), 70 (56), 69 (68), 57 (100), 55 (50). HRMS (ESI) for
C9H17Cl3N3: calcd, 272.0470; found, 272.0483.
Ethyl 3-[(1RS,2RS)-1-Azido-2-(3-oxoheptyl)cyclohexyl]propa-
noate (32). Compound 32 was obtained according to the GP from
ethyl 2-(azidosulfonyl)acetate 1 (1.1 g, 5.76 mmol), 31 (600 mg,
2.88 mmol), and di-tert-butyldiazene (204 mg, 1.44 mmol) in tert-
butyl alcohol (9 mL). The crude product was purified by flash
chromatography (8:1 pentane/Et2O) to afford 32 (863 mg, 82%) as
a light-yellow oil containing a 3:2 mixture of diastereomers in favor
of the desired trans-(1RS,2RS) isomer. 1H NMR (300 MHz, CDCl3):
δ 4.17-4.06 (m, 2H), 2.51-2.22 (m, 6H), 2.12-2.03 (m, 1H),
1.94-1.15 (m, 20H), 0.89 (t, J ) 7.3 Hz, 3H). 13C NMR (75 MHz,
CDCl3): δ 210.9, 210.8, 173.4, 173.0, 66.4, 65.9, 60.6, 60.5, 43.4,
42.5, 42.5, 42.1, 40.9, 40.0, 33.0, 32.8, 32.2, 32.2, 29.4, 28.4, 27.1,
26.6, 26.0, 24.8, 23.8, 23.1, 22.8, 22.3, 22.2, 21.8. IR (neat): 2933,
C is not only extremely short (four steps involving three purifica-
tions from 30 and seven steps from commercially available
pyrrolidinocyclohexene) but also high-yielding (23% overall yield
from pyrrolidinocyclohexene).
Conclusions
By combining the radical precursors and the azidating agent into
a single compound, a highly efficient and atom-economical
carboazidation of alkenes has been accomplished. The desulfony-
lative azide transfer reaction proved to be very efficient with three
sulfonyl azides as well as a large number of terminal alkenes.
Moreover, the reaction takes place under mild conditions with short
reaction times. Interestingly, the yields were noticeably higher than
those obtained using previous methods. The synthetic potential of
the process has been demonstrated by the synthesis of two alkaloids.
The extension of this approach to a broad range of carbon-centered
radicals possessing electrophilic character (activation by one
electron-withdrawing substituent is sufficient) is under investigation
and will be applied to the synthesis of useful scaffolds of biological
interest.
2863, 2093, 1732, 1712, 1455, 1377, 1254, 1177, 1024, 860 cm-1
.
MS (EI) m/z (%): 309 (1, [M - N2]+), 263 (10), 245 (12), 224
(21), 210 (26), 197 (18), 164 (90), 150 (38), 136 (52), 124 (26),
106 (25), 85 (39), 67 (31), 57 (84), 55 (100). HRMS (ESI): calcd
for C18H31O3N3Na, 360.22576; found, 360.22647.
(5RS,7aSR,11aSR)-5-Butyldecahydro-3H-pyrrolo[2,1-j]quinolin-
3-one (33). A mixture of 32 (dr ) 3:2, 600 mg, 1.64 mmol) in ethanol
(16 mL) was hydrogenated at a pressure of 55 bar in the presence of Pd/
CaCO3 (164 mg, 5% w/w) at 100 °C for 3 days. The catalyst was removed
by filtration over Celite, and the solvent was removed under reduced
pressure. The crude product was diluted in (CH2Cl)2 (15 mL). To this
solution was added Me2AlCl (8.2 mL of a 2.4 M solution in 1,2-
dichloroethane, 12 mmol), and the reaction mixture was heated under
reflux for 3 days and then cooled to room temperature. Next, the reaction
mixture was diluted in ice-cold EtOAc (100 mL), and 0.5 M aqueous
Na2HPO4 (4 mL) was cautiously added. The organic layer was dried, and
the solvent was removed under reduced pressure. The crude product was
purified by chromatography (2:1 pentane/Et2O) to afford 33 (160 mg, 0.64
mmol, 39%) as a colorless liquid containing a 10:1 (5RS,7aSR,11aSR)/
(5SR,7aSR,11aSR) mixture of diastereomers. 1H NMR (300 MHz, CDCl3)
(mixture of diastereomers): δ 3.21-3.08 (m, 1H), 2.55-2.38 (m, 2H),
2.11 (dd, J ) 8.7, 16.1 Hz, 1H), 1.92-1.83 (m, 1H), 1.82-1.21 (m, 20
H), 1.20-1.12 (m, 1H), 0.88 (t, J ) 7.1 Hz, 3H). 13C NMR (75 MHz,
CDCl3): (major, 5RS,7aSR,11aSR) δ 176.3, 66.2, 51.7, 42.5, 33.3, 31.6,
30.5, 30.0, 27.2, 26.1, 24.4, 23.5, 22.6, 22.1, 14.1; (minor, 5SR,7aSR,11aSR,
selected peaks) δ 174.8, 64.9, 53.9, 39.9. The 1H and 13C NMR data are
in excellent agreement with those reported in the literature.27
Experimental Section
Caution! Sulfonyl azides are capable of explosion. It is strongly
recommended that standard safety rules be applied and a safety
shield be used.
General Procedure (GP) for the Carboazidation of Alkenes. To
a stirred solution of sulfonyl azide (2.0 equiv) in tert-butyl alcohol or
benzene was added alkene (1.0 equiv) and di-tert-butyldiazene (0.5 equiv)
in a quartz round-bottom flask. The resulting mixture was irradiated with
a 300 W sun lamp and stirred under reflux. The reaction was monitored
by TLC. Upon completion, the organic phase was washed with saturated
aqueous Na2CO3 solution, dried with Na2SO4, and concentrated under
reduced pressure. The crude product was purified by flash chromatography
on silica gel.
Ethyl 3-(1-Azidocyclohexyl)propanoate (5). Compound 5 was
obtained according to the GP from ethyl 2-(azidosulfonyl)acetate 1 (309
mg, 1.6 mmol), methylenecyclohexane (84 mg, 0.8 mmol), and di-tert-
butyldiazene (57 mg, 0.4 mmol) in tert-butyl alcohol (2 mL). The crude
product was purified by flash chromatography (95:5 pentane/EtOAc) to
afford 5 (166 mg, 92%) as a colorless liquid. 1H NMR (300 MHz, CDCl3):
δ 4.14 (q, J ) 7.2 Hz, 2H), 2.42-2.38 (m, 2H), 1.90-1.87 (m, 2H),
1.71-1.65 (m, 2H), 1.62-1.51 (m, 5H), 1.40-1.24 (m, 3H), 1.27 (t, J )
7.2 Hz, 3H). 13C NMR (75 MHz, CDCl3): δ 173.3, 63.3, 60.5, 34.7, 34.4,
Acknowledgment. We thank the Swiss National Science Foundation
(Grants 21-67106.01 and 7SUPJ062348) for financial support.
Supporting Information Available: Experimental procedures,
1
characterization data, and copies of H and 13C NMR spectra
of all new compounds. This material is available free of charge
JA1068036
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J. AM. CHEM. SOC. VOL. 132, NO. 49, 2010 17515