P. Renaud et al.
ꢀ788C to RT. Filtration of the crude reaction mixture over a pad of silica
gel then short flash chromatography on silica gel (100:0, 98:2, 90:10 pen-
tane/Et2O) gave crude 2a contaminated by side-product 9a (4%) (GC
evaluation). Purification by a second flash chromatography (pentane/0–
1% Et2O) afforded 2a (511 mg, 58%) as a pale-yellow liquid.
lution immediately turned a dark-yellow colour. The reaction mixture
was stirred at 08C for 1 h and then at RT for 3.5 h. The mixture was ex-
tracted with Et2O. The combined organic layers were washed with water
and brine then dried over anhydrous Na2SO4, filtered and the solvents
were removed under reduced pressure. Purification by flash chromatog-
raphy (98:2 pentane/Et2O) afforded 16 (59 mg, 82%) as a dark-yellow
liquid.
Method b: One-pot procedure from cyclohexene (1–8 mmol scale): Cate-
cholborane (1.7 mL, 16 mmol) was added to a solution of cyclohexene
(0.81 mL, 8 mmol) and N,N-dimethylacetamide (0.11 mL, 1.2 mmol) in
CH2Cl2 (16 mL). The mixture was stirred at 408C for 5 h. After cooling
to 08C, tert-butanol (0.75 mL, 8 mmol) was added to solvolyse the excess
of catecholborane. Hydrogen evolution was observed. The solution was
stirred at RT for 30 min and then further diluted with CH2Cl2 (9 mL).
The reaction mixture was cooled to ꢀ788C and a solution of tetranitro-
methane (1.57 g, 8 mmol) in CH2Cl2 (10 mL) was cautiously added
through a dropping funnel over a period of 25 min. A yellow colouration
of the reaction mixture was observed after addition of the first few drops.
With further addition the reaction mixture turned a dark-brown colour
and some brown vapour was observed. After complete addition, more
CH2Cl2 (3 mL) was added and the reaction was stirred at ꢀ788C for
5 min. The cooling bath was removed and the mixture allowed to warm
to RT. The reaction mixture turned black immediately and was stirred
overnight at RT. The mixture was purified by flash chromatography on
silica gel (99:1, 95:5, 90:10 cyclohexane/tert-butyl methyl ether) afforded
2a (839 mg, 48%) as a pale yellow liquid (contaminated by traces of
side-product 9a). 1H NMR (400 MHz, CDCl3): d=4.56–4.48 (m, 1H),
2.04–1.97 (m, 2H), 1.81–1.71 (m, 2H), 1.68–1.51 (m, 3H), 1.45–1.26 ppm
(m, 3H); 13C NMR (100 MHz, CDCl3): d=146.6 (br), 89.8, 30.9, 25.0,
23.3 ppm; 14N NMR (36 MHz, CDCl3): d=ꢀ18.8 (br, 1N; oxime N, exact
value taken from the 15N-trace of the 1H/15N-HMBC spectra), ꢀ32.9 (s,
1N; NO2), ꢀ40.9 ppm (s, 1N; NO2); IR (film): n˜ =2942, 2863, 1557, 1451,
1322, 1050, 1004 cmꢀ1; MS (EI, 70 eV): m/z (%): 171 [M+ꢀNO2] (2), 98
(10), 83 (99), 67 (30), 55 (100); elemental analysis calcd (%) for
C7H11N3O5: C 38.71, H 5.10, N 19.35; found: C 38.85, H 5.04, N 19.47.
Method b: One-pot synthesis from 3a: A solution of tetranitromethane
(1 mmol) in CH2Cl2 (1.5 mL) was added cautiously to a solution of 3a
(213 mg, 1.05 mmol) in CH2Cl2 (3.2 mL) at ꢀ788C over a period of
10 min. After complete addition, more CH2Cl2 (0.5 mL) was added. The
reaction mixture was stirred overnight and allowed to warm up slowly
from ꢀ788C to RT. At 08C, piperidine (4 mmol) was slowly added. Some
brown vapour was observed. The mixture was stirred at 08C for 1 h and
then at RT for 4 h. The dark mixture was purified by flash chromatogra-
phy on silica gel (98:2, 96:4 pentane/Et2O) to afford 16 (162 mg, 61%) as
1
a dark-yellow liquid. H NMR (400 MHz, CDCl3): d=4.08–4.02 (m, 1H),
3.17–3.15 (m, 4H), 1.96–1.92 (m, 2H), 1.73–1.61 (m, 8H), 1.55–1.44 (m,
3H), 1.40–1.25 ppm (m, 3H); 13C NMR (100 MHz, CDCl3): d=82.8, 48.6,
31.3, 25.7, 25.6, 23.9, 23.6 ppm; IR (film): n˜ =2933, 2856, 1656, 1543,
1450, 1200, 993 cmꢀ1; MS (EI, 70 eV): m/z (%): 255 [M]+ (3), 209 (20),
127 (35), 111 (77), 99 (9), 81 (41), 69 (34), 55 (100), 41 (58); elemental
analysis calcd (%) for C12H21N3O3: C 56.45, H 8.29, N 16.46; found: C
56.48, H 8.37, N 16.44.
Acknowledgements
This work was supported by the Swiss National Science Foundation
(grant numbers 21-67106.01 and 7SUPJ062348). We thank BASF Corpo-
ration for a donation of chemicals and Dr. Kandhasamy Sarkunam for
running preliminary experiments that triggered our study.
CyclohexylACHTUNGTRENNUNG(nitro)methanone O-cyclohexyl oxime (9a): Compound 3a
(96 mg, 0.475 mmol) was added to a solution of 2a (87 mg, 0.4 mmol) in
CH2Cl2 (1 mL) at 08C. The solution turned yellow, then brown and final-
ly black. The reaction mixture was stirred at 08C for 3 h and then at RT
for 4 h. The black mixture was purified by flash chromatography on silica
gel (100:0, 98:2 pentane/Et2O). Residual starting material was removed
by a second flash chromatography (pentane/0–1% Et2O) to afford 9a
(30 mg, 30%, E/Zꢁ1:1) as a yellow liquid. 1H NMR (300 MHz, CDCl3):
d=4.24–4.15 (m, 1H), 4.12–4.03 (m, 1H), 3.21–3.11 (m, 1H), 2.64–2.54
(m, 1H), 1.99–1.64 (m, 20H), 1.57–1.20 ppm (m, 20H); 13C NMR
(75 MHz, CDCl3): d=164.7, 156.1, 84.2, 82.8, 38.7, 37.0, 31.3, 31.1, 29.3,
27.7, 26.1, 25.63, 25.61, 25.60, 25.55, 25.4, 23.6, 23.5 ppm; IR (film): n˜ =
2933, 2856, 1539, 1450, 1046, 983 cmꢀ1; MS (EI, GC-MS, 70 eV): m/z
(%): first isomer: 208 [M+ꢀNO2] (3), 126 (100), 98 (8), 93 (18), 83 (43),
67 (27), 55 (52), 41 (38); second isomer: 208 [M+ꢀNO2] (2), 126 (32), 98
(4), 93 (8), 83 (100), 67 (14), 55 (54), 41 (29).
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GC determination of yield from 2a: At 08C, a solution of 3a (206 mg,
1.02 mmol) in CH2Cl2 (1 mL) was added to a solution of 2a (111 mg,
0.51 mmol) in CH2Cl2 (1 mL). The mixture was stirred at RT for 19 h.
Undecane (100 mL, 0.473 mmol) was added to the black reaction mixture
as a standard for yield determination by GC (GC: HP-5890; column: HP
Ultra 2, length: 10 m; pressure: 0.80 bar; starting temperature: 408C,
hold: 1 min, rate: 68Cminꢀ1). Yield of 9a=57%, E/Z or Z/E = 1:1.03;
retention time (tR)=23.2 and 23.7 min.
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GC determination of yield from tetranitromethane: At ꢀ788C, a solution
of tetranitromethane (100 mg, 0.5 mmol) in CH2Cl2 (0.75 mL) was added
cautiously to a solution of 3a (410 mg, 2 mmol) in CH2Cl2 (1.7 mL) over
a period of 10 min. More CH2Cl2 (0.3 mL) was added after complete ad-
dition. The dry-ice bath was removed and the black mixture was stirred
at RT for 15 h. Undecane (100 mL, 0.473 mmol) was added to the reac-
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56%, E/Z or Z/E = 1:1.07.
Nitro(piperidin-1-yl)methanone O-cyclohexyl oxime (16)
Method a: Synthesis from 2a: Piperidine (70 mL, 0.71 mmol) was added
to a solution of 2a (62 mg, 0.28 mmol) in CH2Cl2 (1 mL) at 08C. The so-
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10176
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Chem. Eur. J. 2010, 16, 10171 – 10177