11610
W. M. De Borggraeve et al. / Tetrahedron 60 (2004) 11597–11612
(d, 3H, JZ6.8 Hz, CH(CH3)2), 1.06 (d, 3H, JZ6.8 Hz,
CH(CH3)2); 13C NMR (100 MHz, CDCl3, ppm): 174.2
(COOCH3), 171.8 (CONHCH3), 170.2 (CO), 66.5 (C5),
58.5 (C2), 52.8 (OCH3), 34.8 (NCH3), 33.8 (CH(CH3)2),
28.6 (CH2), 27.5 (CH3), 26.4 (CH2), 24.3 (COCH3),
19.3 (CH(CH3)2), 18.6 (CH(CH3)2); EIMS m/z (%): 241
(M8CKCOCH%3, 81), 225 (M8CKCOOCH%3, 29), 212
(M8CKCH3NCOCH%3, 67), 199 (100).
(COCH3), 24.8 (CH3), 24.1 (CH3); EIMS m/z (%): 242
(M8C, 2), 183 (M8CKCOOCH$3, 100), 141 (C7H13N2OC,
41), 124 (C7H10NOC, 36); HRMS: calcd for C11H18N2O4:
242.1267; Found: 242.1278.
7.7.7. Methyl 5-(acetylamino)-1-benzyl-5-methyl-6-oxo-
2-piperidinecarboxylate (8g). Yield: 91%; melting point:
137 8C (hexane/CH2Cl2); IR (KBr) cmK1: 1738 (s, CO),
1
1666 (br s, CO); H NMR (CDCl3, 400 MHz): 7.36–7.26
7.7.3. Methyl 5-(acetylamino)-5-isopropyl-2-methyl-6-
oxo-2-piperidinecarboxylate (8c). Yield: 62%; melting
(m, 3H, PhH), 7.19–7.15 (m, 2H, PhH), 6.58 (s, 1H, NH),
5.49 (d, 1H, JZ15 Hz, CH2Ph), 3.97 (dd, 1H, JZ4 Hz,
3 Hz, H2), 3.76 (s, 3H, OCH3), 3.70 (d, 1H, JZ15 Hz,
CH2Ph), 2.72–2.60 (m, 1H, CH2), 2.17–2.03 (m, 3H,
CH2CH2), 1.97 (s, 3H, CH3), 1.63 (s, 3H, CH3); 13C NMR
(CDCl3, 100 MHz): 173.4 (CO), 171.6 (CO), 169.7 (CO),
136.2 (ArC), 128.8; 128.1; 127.8 (ArCH), 58.4 (C2), 56.8
(C5), 52.6 (OCH3), 50.1 (CH2Ph), 29.9 (CH2), 24.8 (CH3),
24.1 (CH3), 23.0 (CH2); EIMS m/z (%): 318 (M8C, 32), 259
(M8CKNH2COCH3, 49), 231 (M8CKNH2COCH3–CO,
100), 91 (PhCHC2 , 98); HRMS: calcd for C17H22N2O4:
318.1580; Found: 318.1578.
1
point: oil; H NMR (400 MHz, CDCl3, ppm): 6.00 (s, 1H,
NH), 5.94 (s, 1H, NH), 3.79 (s, 3H, OCH3), 2.46–2.43 (m,
1H, CH2K4), 2.41–2.38 (m, 1H, CH2-3), 2.27–2.22 (m, 1H,
CH2K4), 2.19 (heptuplet, 1H, CH(CH3)2), 1.95 (s, 3H,
CH3CO), 1.83 (dt, 1H, JZ12.6, 10.5 Hz, CH2-3), 1.43 (s,
3H, CH3), 1.03 (d, 3H, CH(CH3)2), 1.00 (d, 3H, CH(CH3)2);
13C NMR (100 MHz, CDCl3, ppm): 174.0 (COOCH3),
173.3 (CONH), 169.7 (COCH3), 61.1 (C5), 59.7 (C2), 53.0
(OCH3), 35.0 (CH(CH3)2), 29.2 (CH2K5), 27.4 (CH3), 24.9
(CH2-4), 24.1 (CH3CO), 18.2 (CH(CH3)2), 17.0 (CH(CH3)2).
7.7.4. Methyl 5-(acetylamino)-1-(4-methoxybenzyl)-2,5-
dimethyl-6-oxo-2-piperidinecarboxylate (8d). Yield:
75%; melting point: oil; 1H NMR (400 MHz, CDCl3,
ppm): 7.09 (d, 2H, JZ8.6 Hz, Hortho), 6.82 (d, 2H, JZ
8.6 Hz, Hmeta), 6.74 (s, 1H, NH), 5.22 (d, 1H, JZ15.8 Hz,
CH2Ph), 3.81 (d, 1H, JZ15.8 Hz, CH2Ph), 3.77 (s, 3H,
OCH3), 3.74 (s, 3H, COOCH3), 2.74–2.72 (m, 1H, CH2),
2.22–2.18 (m, 1H, CH2), 2.05–2.01 (m, 2H, CH2), 1.96 (s,
3H, COCH3), 1.65 (s, 3H, CH3K5), 1.48 (s, 3H, CH3-2);
13C NMR (100 MHz, CDCl3, ppm): 174.6 (CO), 173.9
(COOCH3), 169.7 (COCH3), 158.5 (Cpara), 130.7 (Cipso),
128.1 (Cortho), 114.1 (Cmeta), 65.7 (C5), 56.4 (C2), 55.2
(OCH3), 52.9 (COOCH3), 48.1 (CH2Ph), 32.5 (CH2), 29.4
(CH2), 25.7 (CH3K2), 24.7 (CH3-5), 24.2 (COCH3); EIMS
m/z (%): 362 (M8C, 15), 275 (C16H21NOC3 , 22), 136
(C8H10NOC, 100), 121 (C8H9OC, 92); HRMS: calcd for
C19H26N2O5: 362.1842; Found: 362.1854.
7.7.8. Ethyl 5-(acetylamino)-1-benzyl-2-methyl-6-oxo-5-
phenyl-2-piperidinecarboxylate (8h). Yield: 82%; melting
point: 61 8C (CH2Cl2/hexane); IR (KBr) cmK1: 1722 (s,
CO), 1636 (s, CO); 1H NMR (CDCl3, 400 MHz): 7.48–7.25
(m, 10H, PhH), 7.23 (s, 1H, NH), 5.26 (d, 1H, JZ16 Hz,
CH2Ph), 4.22 (q, 2H, JZ7 Hz, OCH2), 3.97 (d, 1H, JZ
16 Hz, CH2Ph), 3.35 (ddd, 1H, JZ14 Hz, 1.5 Hz, 1.5 Hz,
H3eq or H4eq), 2.48 (ddd, 1H, JZ14 Hz, 14 Hz, 1.5 Hz,
H3ax or H4ax), 2.14 (ddd, 1H, JZ14 Hz, 1.5 Hz, 1.5 Hz,
H3eq or H4eq), 1.90 (ddd, 1H, JZ14 Hz, 14 Hz, 1.5 Hz,
H3ax or H4ax), 1.91 (s, 3H, COCH3), 1.44 (s, 3H, CH3), 1.29
(t, JZ7 Hz, 3H, CH3); 13C NMR (CDCl3, 100 MHz): 173.3
(CO), 172.0 (CO), 169.2 (CO), 140.6 and 138.1 (PhCipso),
126.9–128.5 (ArC), 66.1 (C5), 62.3 (OCH2), 62.1 (C2), 49.7
(CH2Ph), 31.2 (C3 or C4), 27.8 (C3 or C4), 25.7 (CH3), 24.4
(COCH3), 14.2 (CH3); EIMS m/z (%): 408 (M8C, 14), 335
(86), 91 (PhCHC2 , 100) HRMS: calcd for C24H28N2O4:
408.2049; Found: 408.2055.
7.7.5. Methyl 5-(acetylamino)-1,2,5-trimethyl-6-oxo-2-
piperidinecarboxylate (8e). Yield: 68%; melting point:
For the spectral data of compound 8i we refer to Ref. 21.
1
oil; H NMR (400 MHz, CDCl3, ppm): 6.62 (s, 1H, NH),
3.76 (s, 3H, OCH3), 2.88 (s, 3H, NCH3), 2.70–2.68 (m, 1H,
CH2), 2.22–2.19 (m, 1H, CH2), 1.99–1.96 (m, 2H, CH2C
CH2), 1.95 (s, 3H, COCH3), 1.57 (s, 6H, CH3); 13C NMR
(100 MHz, CDCl3, ppm): 173.8 (CONCH3), 173.6
(COOCH3), 169.6 (CONH), 64.5 (C2), 56.4 (C5), 52.9
(OCH3), 32.1 (CH2), 30.9 (NCH3), 29.2 (CH2), 25.1 (CH3),
24.3 (CH3), 24.3 (CH3CO); EIMS m/z (%): 197 (M8CK
CH3CONH2, 100), 138 ((M8CKCH3CONH2)–COOCH$3,
22).
7.7.9. Methyl 5-(acetylamino)-5-benzyl-1-(4-methoxy-
benzyl)-6-oxo-2-piperidinecarboxylate (8j). Yield: 75%;
melting point: oil; IR (NaCl, cmK1): 3397 (NH), 1747 (CO),
1652 (CO); 1H NMR (CDCl3, 400 MHz): 7.22–7.18 (m 3H,
ArH), 7.14 (d, 2H, JZ8.5 Hz, ortho PMB), 7.05–6.98 (m,
2H, Ar H), 6.87 (d, 2H, JZ8.5 Hz, meta PMB), 6.45 (s, 1H,
NH), 5.29 (s, 1H, JZ14.5 Hz, N–CH of PMB), 3.95 (br d,
1H, JZ5 Hz, H2), 3.81 (s, 3H, Ar-OCH3), 3.76–3.68 (m,
4H, CH3–O–COCN–CH of PMB), 3.41 (d, 1H, JZ13 Hz,
Ph-CH–C5), 3.14 (d, 1H, JZ13 Hz, Ph-CH–C5), 2.83 (br d,
1H, JZ14 Hz, H4eq), 2.15 (ddd, 1H, JZ14, 14, 4 Hz,
H4ax), 2.01–1.89 (m, 4H, NHCOCH3CH3eq), 1.8 (dddd,
1H, JZ14, 14, 6, 4 Hz, H3ax); 13C NMR (CDCl3,
100 MHz): 171.7, 171.6 (C6 and COOCH3), 169.7
(CONH), 159.3 (Cpara-PMB), 135.9 (ipso-Bn), 130.3,
130.1, 128, (Ar CH), 127.9 (ipso-PMB), 126.9 (ArCH),
114.0 (meta PMB), 60.3 (C5), 58.5 (C2), 55.2 (Ar OCH3),
52.5 (COOCH3), 50.0 (N–CH2 of PMB), 43.1 (C5–CH2-
Ph), 29.2 (C4), 24.1 (CH3CONH), 22.8 (C3); EIMS m/z (%):
424 (6, M8C), 333 (19, M8CKC6H5–CH%2), 121 (100,
7.7.6. Methyl 5-(acetylamino)-2,5-dimethyl-6-oxo-2-
piperidinecarboxylate (8f). Yield: 37%; melting point:
1
155 8C; H NMR (300 MHz, CDCl3, ppm): 6.27 (s, 1H,
NH), 5.97 (s, 1H, NH), 3.80 (s, 3H, OCH3), 2.48–2.43 (dm,
1H, JZ14 Hz, CH2eq), 2.30 (dt, 1H, JZ14.0, 3.7 Hz,
CH2eq), 2.18 (td, 1H, JZ13.8, 3.7 Hz, CH2ax), 1.95 (s, 3H,
COCH3), 1.78 (td, 1H, JZ13.8, 4.4 Hz, CH2ax), 1.54 (s, 3H,
CH3), 1.45 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3, ppm):
174.7 (CO), 174.3 (CO), 170.1 (CO), 60.4 (C2/C5), 55.7
(C2/C5), 53.4 (OCH3), 30.8 (CH2), 30.3 (CH2), 27.9