2372
E. Kleinpeter et al. / Tetrahedron 68 (2012) 2363e2373
Rf¼0.64 (hexane/ethyl acetate 1:3); 1H NMR (300 MHz, CDCl3)
CDCl3)
d
¼29.7, 36.6 (2t, C-2,6, C-3,5), 64.3 (d, C-1), 72.0 (d,
d
¼1.18e2.01 (m, 4H, 6-H, 2-H), 2.20e2.30 (m, 2H, 3-H), 2.50e2.57
CHCl2), 163.6 (s, COCHCl2), 208.6 (s, C-4). IR (film):
n
¼2960, 1756,
(m, 2H, 5-H), 2.59 (s, 1H, OH), 4.10e4.15 (m, 1H, 1-H); 13C NMR
(300 MHz, CDCl3)
1709, 1277, 1167, 965, 891, 812, 681 cmꢁ1; elemental analysis
calcd (%) for C8H10Cl2O3 (225.07): C 42.69, H 4.48; found: C
42.82, H 4.48.
d
¼33.5, 37.1 (2t, C-2,6, C-3,5), 65.9 (d, C-1), 211.6
(s, C-4) in accordance to literature.
4.3. Synthesis of esters 3e16
4.3.7. 4-Oxo-cyclohexyl trichloroacetate (13). Rf¼0.75 (hexane/
ethyl acetate 1:1); 1H NMR (300 MHz, CDCl3)
d¼2.12e2.17 (m, 2H,
4-Hydroxy-cyclohexanone 1 (2.0 mmol) was dissolved in 3 mL
of pyridine at 0 ꢂC. The corresponding acid chloride 2 (1.5 equiv)
was added drop-wise at this temperature over a period of 30 min.
After stirring for 12 h at room temperature, the mixture was di-
rectly poured on a column of silica gel and purified by flash chro-
matography (hexane/ethyl acetate 1:1). The esters 3e16 were
isolated as colorless oils in analytically pure form in the yields given
in Table 1.
3-H), 2.27e2.35 (m, 2H, 5-H), 2.35e2.44 (m, 2H, 2-H), 2.56e2.67
(m, 2H, 6-H), 5.30e5.34 (m, 1H, 1-H); 13C NMR (300 MHz, CDCl3)
d
¼29.7, 36.6 (2t, C-3,5, C-2,6), 68.6 (q, CCl3), 74.1 (d, C-1), 177.4 (s,
COCCl3), 208.4 (s, C-4). IR (film):
n
¼2960, 2571, 1759, 1682, 1236,
824, 674 cmꢁ1; elemental analysis calcd (%) for C8H9Cl3O3 (25.519):
C 37.03, H 3.50; found: C 37.18, H 3.43.
4.3.8. 4-Oxo-cyclohexyl propanoate (4). Rf¼0.75 (hexane/ethyl ac-
etate 1:1); 1H NMR (300 MHz, CDCl3)
d
¼0.98 (t, J¼7.5 Hz, 3H, CH3),
4.3.1. 4-Oxo-cylohexyl acetate (3). Rf¼0.56 (hexane/ethyl acetate
1.86e1.93 (m, 4H, 3-H, 5-H), 2.15e2.22 (m, 2H, 2-H), 2.21 (q,
J¼7.5 Hz, 2H, CH2CH3), 2.31e2.41 (m, 2H, 2-H, 6-H), 4.96e5.03 (m,
1:1); 1H NMR (300 MHz, CDCl3)
d
¼1.98e2.08 (m, 4H, 3-H, 5-H),
2.04 (s, 3H, COCH3), 2.26e2.35 (m, 2H, 2-H), 2.43e2.54 (m, 2H, 6-
1H,1-H); 13C NMR (300 MHz, CDCl3)
d
¼8.7 (s, CH3), 27.4 (t, CH2CH3),
H), 5.11 (Quintet, J¼5 Hz, 1H, 1-H); 13C NMR (300 MHz, CDCl3)
30.0, 36.8 (2t, C-3,5, C-2,6), 68.0 (d, C-1), 173.2 (s, COCH2CH3), 209.0
d
¼21.1 (s, COCH3), 30.3, 37.1 (2t, C-2,6, C-3,5), 68.5 (d, C-1), 170.2 (s,
(s, C-4). IR (film):
mental analysis calcd (%) for C9H14O3 (170.21): C 63.51, H 8.29;
found: C 63.41, H 8.25.
n
¼2945, 1716, 1180, 1085, 1000, 885 cmꢁ1; ele-
COCH3), 209.6 (s, C-4). IR (film):
n
¼2956, 1716, 1375, 1231, 1037, 955,
608 cmꢁ1; elemental analysis calcd (%) for C8H12O3 (156.18): C
61.52, H 7.74; found: C 61.79, H 7.97.
4.3.9. 4-Oxo-cyclohexyl pentanoate (7). Rf¼0.75 (hexane/ethyl ac-
4.3.2. 4-Oxo-cyclohexyl trifluoroacetate (10). Rf¼0.66 (hexane/ethyl
etate 1:1); 1H NMR (300 MHz, CDCl3)
d
¼0.86 (t, J¼7.4 Hz, 3H,
acetate 1:1); 1H NMR (300 MHz, CDCl3)
d
¼2.06e2.17 (m, 4H, 3-H, 5-
CH3), 1.24e1.36 (m, 2H, CH2), 1.52e1.62 (m, 2H, CH2), 1.97e2.04
(m, 4H, 3-H, 5-H), 2.25e2.34 (m, 4H, 2-H, CH2), 2.42e2.53 (m, 2H,
H), 2.25e2.34 (m, 2H, 2-H), 2.42e2.52 (m, 2H, 6-H), 5.25e5.32 (m,
1H, 1-H); 13C NMR (300 MHz, CDCl3)
d
¼29.4, 36.2 (2t, C-2,6, C-3,5),
6-H), 5.08e5.15 (m, 1H, 1-H); 13C NMR (300 MHz, CDCl3)
d
¼13.5
73.3 (d, C-1), 116.2 (q, J¼285 Hz, COCF3), 156.7 (q, J¼42.3 Hz, COCF3),
(s, CH3), 22.1, 27.0 (2t, CH2), 30.3 (t, C-2,6), 34.1 (t, CH2), 37.1 (t, C-
3,5), 68.1 (d, C-1), 173.0 (s, COCH2), 209.7 (s, C-4). IR (film):
208.8 (s, C-1). IR (film):
n
¼2948, 1780, 1705, 1148, 939, 841 cmꢁ1
;
MS (ESI): m/z calcd for C8H9F3O3: [MþH]þ: 211.0537; found:
n
¼2960, 2870, 1716, 1182, 1167, 1090, 1023, 941 cmꢁ1; elemental
211.0586.
analysis calcd (%) for C11H18O3 (198.26): C 66.64, H 9.15; found: C
66.48, H 8.99.
4.3.3. 4-Oxo-cyclohexyl bromoacetate (14). Rf¼0.53 (hexane/ethyl
acetate 1:1); 1H NMR (300 MHz, CDCl3)
d
¼2.02e2.17 (m, 4H, 3-H, 5-
4.3.10. 4-Oxo-cyclohexyl 3-methyl-butanoate (8). Rf¼0.75 (hexane/
H), 2.30e2.40 (m, 2H, 2-H), 2.50e2.61 (m, 2H, 6-H), 3.84 (s, 2H,
CH2Br), 5.17e5.24 (m, 1H, 1-H); 13C NMR (300 MHz, CDCl3)
¼25.8
(t, CH2Br), 30.0, 36.9 (2t, C-2,6, C-3,5), 70.5 (d, C-1), 166.5 (s,
ethyl acetate 1:1); 1H NMR (300 MHz, CDCl3)
d¼0.81 (d, J¼6.5 Hz,
d
6H, CH(CH3)2), 1.87e1.98 (m, 5H, 3-H, 5-H, CH(CH3)2), 2.03e2.08
(m, 2H, COCH2), 2.17e2.24 (m, 2H, 2-H), 2.32e2.40 (m, 2H, 6-H),
COCH2Br), 209.1 (s, C-4). IR (film):
n
¼2958, 1714, 1278, 1165,
5.02 (Quintet, J¼4.8 Hz,1H,1-H); 13C NMR (300 MHz, CDCl3)
¼22.0
d
964 cmꢁ1; elemental analysis calcd (%) for C8H11BrO3 (235.08): C
40.87, H 4.72; found: C 40.92, H 4.68.
(2s, CH3), 25.5 (d, CH(CH3)2), 30.1, 36.9 (2t, C-3,5, C-2,6), 42.2 (t,
COCH2), 68.0 (d, C-1), 172.0 (s, COCH2), 209.2 (s, C-4). IR (film):
n
¼2958, 2872, 1718, 1184, 1167, 1088, 1025, 939 cmꢁ1; elemental
4.3.4. 4-Oxo-cyclohexyl tribromoacetate (16). Rf¼0.50 (hexane/
analysis C11H18O3 (198) calcd (%) C 66.64, H 9.15 and found C 64.91,
H 9.24; MS (ESI): m/z: calcd for C11H18O3: [MþH]þ: 199.1334;
found: 199.1329.
ethyl acetate 1:1); 1H NMR (300 MHz, CDCl3)
3-H), 2.31e2.38 (m, 2H, 5-H), 2.43e2.50 (m, 2H, 2-H), 2.63e2.74
(m, 2H, 6-H), 5.34 (s, 1H, 1-H); 13C NMR (300 MHz, CDCl3)
¼29.6,
36.5 (2t, C-3,5, C-2,6), 73.7 (d, C-1), 89.8 (q, CBr3), 161.1 (s, COCBr3),
d
¼2.11e2.19 (m, 2H,
d
4.3.11. 4-Oxo-cyclohexyl butanoate (5). Rf¼0.75 (hexane/ethyl ace-
212.1 (s, C-4). IR (film):
n
¼2958, 2568, 1743, 1705, 1227, 889, 772,
tate 1:1); 1H NMR (300 MHz, CDCl3)
d
¼0.91 (t, J¼7.3 Hz, 3H, CH3),
608 cmꢁ1; elemental analysis calcd (%) for C8H9Br3O3 (392.87): C
24.46, H 2.31; found: C 24.45, H 2.24.
1.56e1.68 (m, 2H, CH2), 1.98e2.05 (m, 4H, 3-H, 5-H), 2.24e2.35 (m,
4H, 2-H, CH2), 2.43e2.53 (m, 2H, 6-H), 5.09e5.16 (m, 1H, 1-H); 13
NMR (300 MHz, CDCl3)
¼13.5 (s, CH3), 18.4 (t, CH2), 30.2 (t, C-2,6),
C
d
4.3.5. 4-Oxo-cyclohexyl chloroacetate (11). Rf¼0.52 (hexane/ethyl
36.3 (t, CH2), 37.1 (t, C-3,5), 68.1 (d, C-1), 172.8 (s, COCH2), 209.5 (s,
acetate 1:1); 1H NMR (300 MHz, CDCl3)
H), 2.29e2.38 (m, 2H, 2-H), 2.47e2.58 (m, 2H, 6-H), 4.06 (s, 2H,
CH2Cl), 5.18e5.25 (m, 1H, 1-H); 13C NMR (300 MHz, CDCl3)
¼30.0,
36.8 (2t, C-3,5, C-2,6), 40.8 (t, CH2Cl), 70.5 (d, C-1), 166.6 (s,
d
¼2.02e2.15 (m, 4H, 3-H, 5-
C-4). IR (film):
n
¼2962, 2874, 1717, 1246, 1174, 1087, 952, 752 cmꢁ1
;
elemental analysis C10H16O3 (184) calcd (%) C 65.19, H 8.75 and
found C 64.82, H 8.57.
d
COCH2Cl), 209.5 (s, C-4). IR (film):
n
¼2958, 1714, 1308, 1172, 1017,
4.3.12. 4-Oxo-cyclohexyl 2-methylethanoate (6). Rf¼0.75 (hexane/
958, 790 cmꢁ1; elemental analysis calcd (%) for C8H11ClO3 (190.62):
C 50.41, H 5.82; found: C 50.27, H 5.63.
ethyl acetate 1:1); 1H NMR (300 MHz, CDCl3)
d
¼1.11 (d,
J¼7.0 Hz, 6H, CH3), 1.95e2.03 (m, 4H, 3-H, 5-H), 2.23e2.32 (m,
2H, 2-H), 2.41e2.48 (m, 2H, 6-H), 2.51 (q, J¼7.0 Hz, 1H,
CH(CH3)2) 5.05e5.12 (m, 1H, 1-H); 13C NMR (300 MHz, CDCl3)
4.3.6. 4-Oxo-cyclohexyl dichloroacetate (12). Rf¼0.65 (hexane/
ethyl acetate 1:1); 1H NMR (300 MHz, CDCl3)
d
¼2.02e2.21 (m,
d
¼18.8 (s, CH3), 30.2 (t, C-2,6), 34.0 (d, CH(CH3)2), 37.0 (t, C-3,5),
4H, 3-H, 5-H), 2.29e2.38 (m, 2H, 2-H), 2.49e2.60 (m, 2H, 6-H),
5.21e5.27 (m, 1H, 1-H), 5.97 (s, 1H, CHCl2); 13C NMR (300 MHz,
67.9 (d, C-1), 176.1 (s, COCH(CH3)2), 209.6 (s, C-4). IR (film):
n
¼2970, 2875, 1719, 1188, 1154, 1125, 1070, 946, 895 cmꢁ1
;