Y.-J. Li et al. / Tetrahedron 67 (2011) 927e935
931
50.8, 48.2, 44.3, 40.2 (2C), 39.2, 36.1, 29.6, 26.4, 21.2, 21.1, 13.7, 12.1,
7.0; HRMS-EI calcd for C19H31NO4 337.2254, found 337.2261; MS-EI
337 (Mþ, 11), 221 (90), 149 (47), 99 (100).
1230 cmꢀ1; 1H NMR (200 MHz, CDCl3)
d
4.77 (dd, J¼7.3, 3.4 Hz, 1H,
CHOC]O), 3.40 (s, 2H, CH2C]O), 2.86 (hep, J¼6.7 Hz, 2H, N(CH)2),
2.66 (d, J¼14.0 Hz, 1H, ABq, NCHH), 2.56 (q, J¼7.2 Hz, 2H, CH2CH3),
2.27 (d, J¼14.0, 1H, ABq, NCHH), 2.20e1.5 (m, 7H), 1.07 (t, J¼7.2 Hz,
3H, CH2CH3), 0.98 (s, 3H, CCH3), 0.93 (d, J¼6.7 Hz Hz, 12H, N(CH
4.2.7. (1S,2R,4R)-7,7-Dimethylbicyclo [2.2.1] heptane-1-carboxylic
acid diisopropylamide-2-yl 3-oxopentanoate (3g). This was synthe-
sized according to the general procedure, on an 8 mmol scale in 70%
(CH3)2)2), 0.89 (s, 3H, CCH3); 13C NMR (50 MHz, CDCl3)
d 202.7,
166.2, 80.8, 64.8, 51.5, 48.7, 47.9, 47.2 (2C), 45.0, 39.5, 36.2, 30.2,
26.5, 22.0 (2C), 20.6, 19.7, 18.9(2C), 7.2; HRMS-EI calcd for
C21H37NO3 351.2773, found 351.2777; MS-EI 351(Mþ, 12), 336(100),
238(27), 114(78), 85(24), 57(43).
yield. Pale-yellow oil. Rf 0.47 (n-hexane/EtOAc, 2/1); [
1.2, CH2Cl2); IR (CHCl3) 2968, 2930,1739,1718,1627,1273,1259, 761,
a
]
26 ꢀ24.7 (c
D
713 cmꢀ1
;
1H NMR (200 MHz, CDCl3)
d
5.06 (dd, J¼3.5, 3.6 Hz, 1H,
CHOC]O), 4.17 (hep, J¼6.8 Hz,1H, NCH), 3.42 (d, J¼15.1 Hz,1H, ABq,
CHHC]O), 3.30 (d, J¼15.1 Hz, 1H, ABq, CHHC]O), 3.25 (hep,
J¼6.8 Hz, 1H, NCH), 2.52 (m, 2H, CH2CH3), 2.25e1.5 (br, 7H), 1.36 (d,
J¼6.8 Hz, 6H, NCH(CH3)2), 1.28 (s, 3H), 1.10 (s, 3H), 1.05 (d, J¼7.1 Hz,
6H, NCH(CH3)2), 1.03 (t, J¼7.3 Hz, 3H, CH2CH3); 13C NMR (50 MHz,
4.2.12. (1R,2R,4R)-1-Diphenylaminomethyl-7,7-dimethylbicyclo
[2.2.1] hept-2-yl 3-oxopentanoate (3l). This was synthesized
according to the general procedure, on an 8 mmol scale in 64%
yield. Pale-yellow oil. Rf 0.43 (n-hexane/EtOAc, 2/1); [
26
a
]
ꢀ85.1 (c
D
CDCl3)
d
202.8, 169.5, 166.4, 80.1, 59.2, 51.4, 48.5, 47.2, 46.3, 44.6,
1, CH2Cl2); IR (CHCl3) 2977, 2875, 1725, 1712, 1637, 1545, 1376,
40.0, 36.8, 29.7, 29.6, 26.8, 21.8, 21.5, 21.1, 20.5 (2C), 20.5; HRMS-EI
calcd for C21H35NO4 365.2566, found 365.2559; MS-EI 365 (Mþ, 27),
249 (81), 206 (42), 99 (100).
1352 cmꢀ1; 1H NMR (200 MHz, CDCl3)
d
7.25 (d, J¼6.8 Hz, 4H, ArH),
7.22 (dd, J¼7.8, 6.8 Hz, 6H, ArH), 4.51 (dd, J¼7.5, 3.4 Hz, 1H, CHOC]
O), 4.05 (d, J¼15.0 Hz, 1H, ABq, NCHH), 3.85 (d, J¼15.0 Hz, 1H, ABq,
NCHH), 3.10 (s, 2H, CH2C]O), 2.42 (q, J¼5.6 Hz, 2H, CH2CH3),
1.72e0.8 (m, 10H), 1.25 (s, 3H, CCH3), 1.02 (s, 3H, CCH3); 13C NMR
(50 MHz, CDCl3) d 203.7,166.3,149.3 (2C),129.5 (4C),121.7(6C), 80.1,
53.4, 49.2, 48.9, 48.5, 45.5, 39.8, 36.6, 30.6, 27.1, 21.1, 20.3, 7.7;
HRMS-EI calcd for C27H33NO3 419.2460, found 419.2469.
4.2.8. (1S,2R,4R)-7,7-Dimethylbicyclo[2.2.1]
heptane-1-carboxylic
acid diphenylamide-1-yl 3-oxopentanoate (3h). This was synthe-
sized according to the general procedure, on an 8 mmol scale in 62%
yield. Pale-yellow oil. Rf 0.50 (n-hexane/EtOAc, 2/1); [
a
]
26 ꢀ70.0 (c
D
1.0, CH2Cl2); IR (CHCl3) 3010, 2977, 2931, 1738, 1718, 1622, 1255,
4.2.13. (1S,2R,4R)-7,7-Dimethylbicyclo [2.2.1] heptane-1-carboxylic
acid phenylamide-2-yl 3-oxopentanoate (3m). This was synthesized
according to the general procedure, on an 8 mmol scale in 70% yield.
Pale-yellow oil. Rf 0.32 (n-hexane/EtOAc, 2/1); [
754 cmꢀ1 1H NMR (200 MHz, CDCl3)
; d 7.34e7.05 (m, 10H, ArH),
4.37 (dd, J¼7.4, 4.2 Hz,1H, CHOC]O), 3.54 (s, 2H, CH2C]O), 2.58 (q,
J¼7.1 Hz, 2H, CH2CH3), 1.92e0.8 (m, 7H), 1.25 (s, 3H, CCH3), 1.07 (s,
3H, CCH3), 1.04 (t, J¼7.1 Hz, 3H, CH2CH3); 13C NMR (50 MHz, CDCl3)
31
a]
ꢀ34.8 (c 0.4,
D
CH2Cl2); IR (CHCl3) 3411, 2931, 1718, 1675, 1595, 1526, 1440,
1317 cmꢀ1; 1H NMR (200 MHz, CDCl3)
d
7.51 (d, J¼8.1 Hz, 2H, ArH),
d
203.3, 171.5, 166.2, 143.0 (2C), 128.9 (8C), 128.3 (2C), 81.0, 59.3,
51.5, 48.8, 44.7, 39.7, 31.1, 26.5, 21.3, 21.2, 7.2; HRMS-EI calcd for
C27H31NO4 433.2253, found 433.2261.
7.49 (s, 1H, NH), 7.31(dd, J¼8.1, 7.5 Hz, 2H, ArH), 7.09 (t, J¼7.5 Hz, 1H,
ArH), 5.15 (dd, J¼5.9, 5.5 Hz, 1H, CHOC]O), 3.42 (s, 2H, CH2C]O),
2.45 (q, J¼7.3 Hz, 2H, CH2CH3), 2.35e1.03(m, 7H), 1.31 (s, 3H, CCH3),
1.12 (s, 3H, CCH3), 0.96 (t, J¼7.3 Hz, 3H, CH2CH3); 13C NMR (50 MHz,
4.2.9. (1R,2R,4R)-1-Dimethyl aminomethyl-7,7-dimethylbicyclo[2.2.1]
hept-2-yl 3-oxopentanoate (3i). This was synthesized according to
the general procedure, on an 8 mmol scale in 70% yield. Pale-yel-
CDCl3) d 202.99,169.74,166.50,137.73,128.82(2C),124.12,120.11(2C),
80.17, 59.01, 49.05, 48.95, 45.85, 39.24, 36.42, 31.21, 26.62, 21.14,
20.75, 7.26; HRMS-EI calcd for C21H27NO4 357.1940, found 357.1945.
low oil. Rf 0.41 (n-hexane/EtOAc, 2/1); [
a
]
26 ꢀ34.6 (c 1.0, CH2Cl2); IR
D
(CHCl3) 2977, 2892, 1728, 1716, 1637, 1562, 1376, 1231, 1043 cmꢀ1
;
1H NMR (200 MHz, CDCl3)
d 4.9 (m, 1H, CHOC]O), 3.46 (s, 2H,
4.2.14. (1S,2R,4R)-1-(Hydroxydiphenylmethyl)-7,7-dimethylbicyclo
[2.2.1] heptan-2-yl 3-oxopentanoate (3n). This was synthesized
according to the general procedure, on an 8 mmol scale in 75%
CH2C]O), 2.62 (q, J¼7.3 Hz, 2H, CH2CH3), 2.62e2.18 (br, 8H, N
(CH3)2, NCH2), 2.14e1.75 (m, 7H), 1.26 (s, 3H, CCH3), 1.08 (t,
J¼7.3 Hz, 3H, CH2CH3), 0.90 (s, 3H, CCH3); 13C NMR (50 MHz, CDCl3)
yield. Pale-yellow oil. Rf 0.32 (n-hexane/EtOAc, 7/1); [
a
]
26 þ56.9 (c
D
d
203.3, 166.3, 79.9, 56.7, 51.6, 49, 48.2, 47.4 (2C), 44.8, 39.4, 36.4,
0.6, CH2Cl2); IR (CHCl3) 3583, 3054, 2984, 2941, 1744, 1718, 1271,
1256, 761, 710 cmꢀ1; 1H NMR (200 MHz, CDCl3)
d 7.78e7.58 (m, 4H,
30.8, 26.9, 20.5, 19.9, 7.3.; HRMS-EI calcd for C17H29NO3 295.2147,
found 295.2149; MS-EI 295 (Mþ, 10), 180(60), 58(100), 45(17).
ArH), 7.30e7.12 (m, 6H, ArH), 5.24 (dd, J¼7.7, 3.8 Hz, 1H, CHOC]O),
3.07 (d, J¼16.0 Hz, 1H, ABq, CHHC]O), 3.02 (d, J¼16.0 Hz, 1H, ABq,
CHHC]O), 2.35e2.21 (q, J¼7.5 Hz, 2H, CH2CH3), 2.00e1.08 (m, 7H),
1.47 (s, 3H, CCH3), 1.00 (t, J¼7.2 Hz, 3H, CH2CH3), 0.64 (s, 3H, CCH3);
4.2.10. (1R,2R,4R)-1-Diethylamino-methyl-7,7-dimethylbicyclo[2.2.1]
hept-2-yl 3-oxopentanoate (3j). This was synthesized according to
the general procedure, on an 8 mmol scale in 75% yield. Pale-yellow
13C NMR (50 MHz, CDCl3)
d 202.4, 164.3, 149.1, 143.1, 128.2(2C),
26
oil. Rf 0.40 (n-hexane/EtOAc, 2/1); [
a
]
D
ꢀ32.1 (c 1.0, CH2Cl2); IR
127.6, 126.4(2C), 126.1, 125.8, 125.7 (2C), 82.1, 80.8, 58.6, 51.1, 47.7,
47.4, 38.1, 36.1, 30.9, 26.6, 24.2, 22.3, 7.1; HRMS-EI calcd for
C27H32O4 420.2301, found 420.2296; MS-EI 420 (Mþ, 4), 183 (94),
105 (100), 77 (48).
(CHCl3) 2975, 2878, 1728, 1710, 1637, 1545, 1376, 1233 cmꢀ1
NMR (200 MHz, CDCl3)
;
1H
d
4.79 (dd, J¼6.9, 3.1 Hz, 1H, CHOC]O), 3.39
(s, 2H, CH2C]O), 3.11 (q, J¼7.1 Hz, 2H, CH2CH3), 2.62e2.18 (m, 8H, N
(CH2CH3)2, NCH2, CH2CH3), 2.14e1.75 (m, 7H), 1.08 (t, J¼7.1 Hz, 3H,
CH2CH3), 0.95 (t, J¼7.0 Hz, 6H, N(CH2CH3)2), 0.93 (s, 3H, CCH3), 0.87
4.2.15. (1S,2R,4R)-1-(Methoxyphenylmethyl)-7,7-dimethylbicyclo
[2.2.1] hept-2-yl 3-oxopentanoate (3o). This was synthesized
(s, 3H, CCH3); 13C NMR (50 MHz, CDCl3)
d 203.1, 166.4, 80.7, 52.1,
50.6, 49.1, 47.8 (2C), 47.7, 45.2, 39.5, 36.4, 30.7, 26.9, 20.6, 20.0, 11.5
(2C), 7.4; HRMS-EI calcd for C19H33NO3 323.2460, found 323.2467;
MS-EI 323 (Mþ, 15), 308(71), 208(38),86(100), 57(76).
according to the general procedure, on an 8 mmol scale in 76% yield.
29
Pale-yellow oil. Rf 0.44 (n-hexane/EtOAc, 10/1); [
a
]
ꢀ4.2 (c 1.0,
D
CH2Cl2); IR (CHCl3) 3050, 2941, 1737, 1713, 1449 cmꢀ1
;
1H NMR
(200 MHz, CDCl3) 7.77e7.55 (m, 4H, ArH), 7.39e7.24 (m, 6H, ArH),
d
4.2.11. (1R,2R,4R)-1-Diisopropylaminomethyl-7,7-dimethylbicyclo
[2.2.1] hept-2-yl 3-oxopentanate (3k). This was synthesized
4.80 (dd, J¼8.0, 3.4 Hz, 1H, CHOC]O), 3.04 (d, J¼14.0 Hz, 1H, ABq,
CHHC]O), 3.02 (d, J¼14.0 Hz,1H, ABq, CHHC]O), 2.79 (s, 3H, OCH3),
2.41e2.22 (m, 2H, CH2CH3),1.90e0.87 (m, 7H),1.13 (s, 3H, CCH3) 1.01
(t, J¼7.3 Hz, 3H, CH2CH3), 0.63 (s, 3H, CCH3); 13C NMR (50 MHz, CDCl3)
according to the general procedure, on an 8 mmol scale in 80%
26
yield. Pale-yellow oil. Rf 0.40 (n-hexane/EtOAc, 2/1); [
a
]
ꢀ21.8 (c
D
1.0, CH2Cl2); IR (CHCl3) 2972, 2876, 1730, 1712, 1640, 1545, 1376,
d
202.8, 165.8, 140.1, 138.7, 131.4(2C), 129.4(2C), 127.3(2C), 126.8,