anti-N-(3,4-Diacetoxy-6-{2,2,2-trichloroacetylamino}-
cyclohexyl)-2Ј,2Ј,2Ј-trichloroacetamide anti-42
7.13 (1H, br d, J 5.1), 5.23–5.05 (2H, m), 4.24–4.00 (1H, m),
2.20–1.60 (12H, m); δC (75 MHz; CDCl3) 169.4, 168.9, 156.0
(q, J 36.6), 115.6 (q, J 288), 69.4, 68.5. 45.4, 31.5, 26.2, 23.9,
20.7, 20.6; (CI, m/z) 330 (15%), 329 (100); Found (CI) 329.1327
N-[6-(2,2,2-Trichloroacetylamino)cyclohex-3-enyl]-2,2,2-
trichloroacetamide 39 (80 mg, 0.20 mmol) was oxidised using
standard UpJohn conditions and concentrated in vacuo. The
mixture was purified by flash chromatography (EtOAc–petrol,
1 : 1) to afford the title compounds as a pale yellow solid which
was characterised as a mixture of diastereoisomers [3.0 : 1.0
ϩ
(M ϩ NH4 C12H20F3N2O5 requires 329.1324).
N-(1-Methylcyclohex-3-enyl)-2,2,2-trifluoroacetamide 45
To a stirred solution of 1-methylcyclohex-3-enylamine (121 mg,
1.09 mmol) in DCM (50 ml) at room temperature under nitro-
gen was added triethylamine (330 mg, 3.27 mmol) and the solu-
tion was cooled to Ϫ78 ЊC. Trifluoroacetyl chloride (∼1 ml) was
distilled directly into the reaction flask from a lecture bottle.
The reaction mixture was allowed to warm to room temper-
ature over 16 hours. Nitrogen was purged through the solution
for 30 minutes to remove any excess trifluoroacetyl chloride and
the solution was concentrated in vacuo. The crude mixture was
purified by flash chromatography (Et2O–petrol, 1 : 3) to afford
the title compound as a white solid (189 mg, 84%), mp 49–51
ЊC; υmax (film)/cmϪ1 3420, 3055, 3033, 2986, 2929, 2845, 2306,
1724, 1535, 1447, 1423, 1378, 1336, 1266, 1205, 1162; δH (300
MHz; CDCl3) 6.14 (1H, br s), 5.80–5.71 (1H, m), 5.63–5.54
(1H, m), 2.38–1.96 (5H, m), 1.62 (1H, ddd, J 14.9, 8.1 and 6.3),
1.49 (3H, s); δC (75 MHz, CDCl3) 127.0, 122.8, 53.1, 37.4, 30.7,
1
(anti : syn) by H NMR, 109 mg, 100%]; mixture υmax (film)/
cmϪ1 3317, 1745, 1722, 1704, 1517, 1369, 1266, 1235, 1209,
1047; syn-42: δH (300 MHz; DMSO) 8.44 (2H, br s), 5.16–5.00
(2H, m), 4.30–4.10 (2H, m), 2.24–2.10 (2H, m), 2.04–1.87 (8H,
m); δC (75 MHz, CDCl3) 169.8, 161.4, 92.9, 68.9, 48.3, 28.2,
21.3; anti-42: δH (400 MHz; DMSO) 8.72 (2H, br d, J 7.2), 5.25–
5.16 (2H, m), 4.38–4.10 (2H, m) 2.27–2.14 (2H, m), 2.04–1.91
(8H, m); δC (100 MHz, DMSO) 169.8, 161.7, 92.6, 67.4, 47.6,
28.4, 20.8; mixture (CI, m/z) 538 (5%), 334 (50), 237 (20), 94
ϩ
(80), 60 (100); Found (CI) 535.9488 (M ϩ NH4 C14H20Cl6N3O6
requires 535.9483).
syn-N-(3,4-Diacetoxy-6-{2,2,2-trichloroacetylamino}-
cyclohexyl)-2Ј,2Ј,2Ј-trichloroacetamide syn-42
N-[6-(2,2,2-Trichloroacetylamino)cyclohex-3-enyl]-2,2,2-
trichloroacetamide 39 (77 mg, 0.19 mmol) was oxidised using
standard OsO4, TMEDA conditions. The reaction mixture was
concentrated in vacuo and purified by flash chromatography
(EtOAc–petrol, 1 : 1) to afford the title compound as a pale
yellow solid which was characterised as a mixture of diastereo-
isomers [3.0 : 1.0 (syn : anti) by 1H NMR, 102 mg, 100%].
24.4, 22.3 (no C᎐O, no CF ); (CI, m/z) 256 (10%), 225 (100), 94
᎐
3
(45); Found (CI) 208.0949 (M ϩ Hϩ C9H13F3NO requires
208.0949).
anti-N-(1-Methyl-3,4-diacetoxycyclohexyl)-2Ј,2Ј,2Ј-trifluoro-
acetamide anti-46
N-(1-Methylcyclohex-3-enyl)-2,2,2-trifluoroacetamide 45 (100
mg, 0.48 mmol) was oxidised using standard UpJohn condi-
tions and concentrated in vacuo. The mixture was purified by
flash chromatography (Et2O–petrol, 4 : 1) to afford the title
compounds as a colourless oil which was characterised as a
mixture of diastereoisomers (3.5 : 1.0 (anti : syn) by 1H NMR,
152 mg, 97%); mixture: υmax (film)/cmϪ1 3321, 2974, 2945, 1746,
1730, 1714, 1555, 1453, 1370, 1253, 1218, 1210, 1184, 1156,
1050, 1027; anti-46; δH (300 MHz; CDCl3) 6.39 (1H, br s), 5.20–
5.08 (1H, m), 4.97–4.86 (1H, m), 2.40–2.30 (1H, m), 2.24–2.14
(1H, m), 2.12 (3H, s), 2.02 (3H, s), 1.95–1.80 (2H, m), 1.74–1.64
(2H, m), 1.27 (3H, s); δC (75 MHz; CDCl3) 170.2, 170.1, 156.7
(q, J 36.6), 115.3 (q, J 289.3), 68.4, 67.7, 55.8, 35.4, 29.5, 26.6,
24.4, 21.0, 20.8; mixture (CI, m/z) 345 (3%), 344 (20), 343 (100);
N-(Cyclohex-3-enyl)-2,2,2-trifluoroacetamide27 43
To a stirred solution of cyclohex-3-enylamine (1.16 g, 11.9
mmol) in DCM (50 ml) was added triethylamine (3.61 g, 35.7
mmol) at room temperature. The solution was cooled to 0 ЊC
and trifluoroacetic anhydride (3.01 g, 14.3 mmol) was added
dropwise. The reaction mixture was allowed to warm to room
temperature over 16 hours and then concentrated in vacuo onto
silica. The crude product was purified by flash chromatography
(Et2O–petrol, 1 : 5) to yield a yellow solid which was recrystal-
lised to afford the title compound as a beige solid (849 mg,
37%); all data were consistent with that in the literature.
anti-N-(3,4-Diacetoxycyclohexyl)-2Ј,2Ј,2Ј-trifluoroacetamide
anti-44
ϩ
Found (CI) 343.1485 (M ϩ NH4 C13H22F3N2O5 requires
343.1481).
N-(Cyclohex-3-enyl)-2,2,2-trifluoroacetamide 43 (80 mg, 0.42
mmol) was oxidised using standard UpJohn conditions and
concentrated in vacuo. The mixture was purified by flash chro-
matography (Et2O–petrol, 1 : 1) to afford the title compounds
as a colourless oil which were characterised as a mixture of
syn-N-(1-Methyl-3,4-diacetoxycyclohexyl)-2Ј,2Ј,2Ј-trifluoro-
acetamide syn-46
N-(1-Methylcyclohex-3-enyl)-2,2,2-trifluoroacetamide 45 (80
mg, 0.39 mmol) was oxidised using standard OsO4, TMEDA
conditions. The reaction mixture was concentrated in vacuo and
purified by flash chromatography (Et2O–petrol, 4 : 1) to afford
the title compound as a colourless oil which was characterised
1
diastereoisomers [1.0 : 1.0 (syn : anti) by H NMR, 130 mg,
99%]; mixture: υmax (film)/cmϪ1 3319, 2952, 1746, 1730, 1714,
1555, 1443, 1371, 1257, 1234, 1210, 1184, 1160, 1045; anti-44:
δH (400 MHz; CDCl3) 6.37 (1H, br d, J 6.8), 5.39–5.32 (1H, m),
4.85 (1H, ddd, J 7.5, 4.6 and 2.9), 4.26–4.15 (1H, m), 2.23–1.80
(12H, m); δC (75 MHz; CDCl3) 170.5, 170.2, 156.6 (q, J 37.2),
115.6 (q, J 288), 70.7, 68.2, 44.4, 34.2, 29.3, 24.3, 21.0, 20.9;
mixture (CI, m/z) 330 (15%), 329 (100); Found (CI) 329.1331
1
as a mixture of diastereoisomers [3.0 : 1.0 (syn : anti) by H
NMR, 84 mg, 67%]; mixture: υmax (film)/cmϪ1 3331, 2953, 2926,
2853, 1729, 1553, 1451, 1434, 1370, 1249, 1210, 1181, 1155,
1050, 1026; syn-46 δH (300 MHz; CDCl3) 7.10 (1H, br s), 5.50–
5.37 (1H, m), 4.92 (1H, ddd, J 10.8, 4.0 and 3.5), 2.65–2.50 (1H,
m), 2.18 (1H, ddd, J 15.3, 4.6 and 2.9), 2.12 (3H, s), 2.02 (3H, s),
1.94–1.65 (4H, m), 1.54 (3H, s); δC (75 MHz; CDCl3) 170.1,
169.2, 155.7 (q, J 36.0), 115.6 (q, J 290), 70.3, 68.5, 53.6, 39.1,
31.8, 25.4, 22.2, 20.8, 20.6; mixture (CI, m/z) 344 (20%),
343 (100); Found (EI) 325.1137 (Mϩ C13H18F3NO5 requires
325.1137).
ϩ
(M ϩ NH4 C12H20F3N2O5 requires 329.1324).
syn-N-(3,4-Diacetoxycyclohexyl)-2Ј,2Ј,2Ј-trifluoroacetamide
syn-44
N-(Cyclohex-3-enyl)-2,2,2-trifluoroacetamide 43 (80 mg, 0.42
mmol) was oxidised using standard OsO4, TMEDA conditions.
The reaction mixture was concentrated in vacuo and purified by
flash chromatography (Et2O–petrol, 1 : 1) to afford the title
compound as a colourless oil [>25 : 1.0 (syn : anti) by 1H NMR,
127 mg, 98%]; υmax (film)/cmϪ1 3329, 2957, 1745, 1729, 1714,
1426, 1381, 1259, 1231, 1208, 1163, 1048; δH (300 MHz; CDCl3)
N-[6-(2,2,2-Trifluoroacetylamino)cyclohex-3-enyl]-2,2,2-trifluoro-
acetamide 47
To a stirred solution of diamine (500 mg, 4.46 mmol) in DCM
(50 ml) was added triethylamine (2.71 g, 26.8 mmol) at room
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 1 7 3 – 2 1 8 6
2185