J.-B. Behr / Tetrahedron Letters 50 (2009) 4498–4501
2988, 2979, 2934, 1617, 1601, 1513, 1375 cmꢁ1
4501
Tetrahedron Lett. 1998, 39, 825–828; (b) Schuster, M.; Blechert, S. Tetrahedron:
Asymmetry 1999, 10, 3139–3145; (c) Davis, B. G.; Maughan, M. A.; Chapman, T.
M.; Villard, R.; Courtney, S. Org. Lett. 2002, 4, 103–106; (d) Izquierdo, I.; Plaza,
M. T.; Rodríguez, M.; Franco, F.; Martos, A. Tetrahedron 2005, 61, 11697–11704;
(e) Hotchkiss, D. J.; Kato, A.; Odell, B.; Claridge, T. D. W.; Fleet, G. W. J.
Tetrahedron: Asymmetry 2007, 18, 500–512.
;
1H NMR (250 MHz, CDCl3) d
8.05–7.98 (m, 2H, Ar-H), 7.10 (t, 2H, J = 8.6 Hz, Ar-H), 5.51 (d, 1H, J = 5.7 Hz, H-
3), 4.70 (t, 1H, J = 5.7 Hz, H-4), 4.12 (dq, 1H, J = 5.7 7.1 Hz, H-5), 1.53 (d, 3H,
J = 7.1 Hz, 5-CH3), 1.43 (s, 3H, CH3), 1.30 (s, 3H, CH3); 13C NMR (62.5 MHz,
CDCl3) d 168.1 (C@N), 163.3 (d, C–F), 129.4 (d, Ar-C), 127.8 (d, Ar-C), 114.5 (Ar-
C), 111.3 (C(CH3)2), 85.5 (C-3), 79.0 (C-4), 66.7 (C-5), 25.9 (C(CH3)2), 25.1
(C(CH3)2), 13.9 (5-CH3); 19F NMR (235 MHz, CDCl3) ꢁ109.76; ESI-HRMS: calcd
for C14H17NO2F [M+H]+ 250.1243; found 250.1241. Compound 6d, yellow oil;
Rf = 0.45 [CH2Cl2/Et2O (70:30)]; IR (film) 2986, 2933, 1641, 1381, 1372,
12. Behr, J.-B.; Kalla, A.; Harakat, D.; Plantier-Royon, R. J. Org. Chem. 2008, 73,
3612–3615.
13. Defoin, A.; Joubert, M.; Henchel, J.-M.; Strehler, C.; Streith, J. Synthesis 2000,
1719–1726.
1078 cmꢁ1 1H NMR (250 MHz, CDCl3) d 7.38–7.20 (m, 5H, Ar-H), 4.90 (d, 1H,
;
14. March, J. Advanced Organic Chemistry, 4th ed.; Wiley and Sons: New York, 1992.
pp 441–442.
J = 5.6 Hz, H-3), 4.56 (t, 1H, J = 5.6 Hz, H-4), 3.90 (m, 1H, H-5), 2.40 (br s, 2H,
CH2), 1.42 (d, 3H, 5-CH3), 1.40 (s, 3H, CH3), 1.32 (s, 3H, CH3); 13C NMR
(62.5 MHz, CDCl3) d 175.1 (C@N), 136.8 (Ar-C), 130.1 (Ar-C), 129.5 (Ar-C), 127.6
(Ar-C), 112.9 (C(CH3)2), 86.6 (C-3), 80.5 (C-4), 68.3 (C-5), 38.2 (C(CH3)2), 27.7
(C(CH3)2), 27.0 (Ar-CH3), 15.5 (5-CH3); ESI-HRMS: calcd for C15H20NO2 [M+H]+
246.1494; found 246.1498. Compound 6e, yellow oil; Rf = 0.50 [CH2Cl2/Et2O
15. (a) Weidmann, H.; Wolf, N.; Timpe, W. Carbohyd. Res. 1972, 24, 184–187; (b)
Hutchins, R. O.; Kandasamy, D.; Maryanoff, C.; Masilamani, D.; Maryanoff, B. E.
J. Org. Chem. 1977, 42, 82–91; (c) Lonn, H.; Lonngren, J. Carbohydr. Res. 1984,
132, 39–44; (d) Rifé, J.; Ortuno, R. M. Tetrahedron: Asymmetry 1999, 10, 4245–
4260; (e) Furukawa, J.-I.; Kobayashi, S.; Nomizu, M.; Nishi, N.; Sakairi, N.
Tetrahedron Lett. 2000, 41, 3453–3457; (f) Thomas, S.; Huynh, T.; Enriquez-
Rios, V.; Singaram, B. Org. Lett. 2001, 3, 3915–3918.
(70:30)]; IR (film) 2986, 2933, 1642, 1380, 1371, 1078 cmꢁ1
;
1H NMR
(250 MHz, CDCl3) d 7.32–7.26 (m, 5H, Ar-H), 4.90 (d, 1H, J = 5.6 Hz, H-3), 4.61
(t, 1H, J = 5.6 Hz, H-4), 3.91 (m, 1H, H-5), 3.00 (t, 2H, J = 7.8 Hz, CH2), 2.73 (m,
16. Theodore, L. J.; Nelson, W. L. J. Org. Chem. 1987, 52, 1309–1315.
2H, CH2), 1.42 (d, 3H, J = 7.3 Hz, 5-CH3), 1.38 (s, 3H, CH3), 1.30 (s, 3H, CH3); 13
C
17. Compound 6a, yellow oil; Rf = 0.45 [petroleum ether/Et2O (50:50)]; ½a D20
ꢂ
ꢁ156
NMR (62.5 MHz, CDCl3) d 175.3 (C@N), 141.7 (Ar-C), 128.8 (Ar-C), 128.7 (Ar-C),
126.5 (Ar-C), 112.5 (C(CH3)2), 87.9 (C-3), 80.2 (C-4), 67.9 (C-5), 32.5 (2 ꢃ CH2),
27.3 (C(CH3)2), 26.6 (C(CH3)2), 15.2 (5-CH3); ESI-HRMS: calcd for C16H22NO2
[M+H]+ 260.1651; found 260.1644. Compound 9, yellow oil; Rf = 0.60
[petroleum ether/Et2O (40:60)]; IR (film) 2987, 2935, 1664, 1597, 1373,
(c 0.22, CHCl3); IR (film) 2995, 2926, 1612, 1446, 1381, 1371 cmꢁ1
;
1H NMR
(250 MHz, CDCl3) d 8.04–7.99 (m, 2H, Ar-H), 7.49–7.42 (m, 3H, Ar-H), 5.50 (d,
1H, J = 5.5 Hz, H-3), 4.79 (t, 1H, J = 5.5 Hz, H-4), 4.14 (dq, 1H, J = 5.5 7.1 Hz, H-
5), 1.48 (d, 3H, J = 7.1 Hz, 5-CH3), 1.44 (s, 3H, CH3), 1.29 (s, 3H, CH3); 13C NMR
(62.5 MHz, CDCl3) d 170.2 (C@N), 130.7 (Ar-C), 128.5 (Ar-C), 128.3 (Ar-C), 112.3
(C(CH3)2), 86.6 (C-3), 79.9 (C-4), 67.8 (C-5), 26.9 (C(CH3)2), 26.2 (C(CH3)2), 14.2
(5-CH3); ESI-HRMS: calcd for C14H18NO2 [M+H]+ 232.1338; found 232.1333.
1233, 1073 cmꢁ1 1H NMR (250 MHz, CDCl3) d 8.22 (d, 2H, J = 5.6 Hz 7.25 (m,
;
5H, Ar-H), 4.90 (d, 1H, J = 5.6 Hz, H-3), 4.61 (t, 1H, J = 5.6 Hz, H-4), 3.91 (m, 1H,
H-5), 3.00 (t, 2H, J = 7.8 Hz, CH2), 2.73 (m, 2H, CH2), 1.42 (d, 3H, J = 7.3 Hz, 5-
CH3), 1.38 (s, 3H, CH3), 1.30 (s, 3H, CH3); 13C NMR (62.5 MHz, CDCl3) d 190.7
(C@O), 170.5 (C@N), 135.8 (Ar-C), 134.3 (Ar-C), 130.8 (Ar-C), 128.9 (Ar-C),
112.7 (C(CH3)2), 86.8 (C-3), 79.2 (C-4), 70.5 (C-5), 27.4 (C(CH3)2), 25.9 (C(CH3)2),
15.0 (5-CH3); ESI-HRMS: calcd for C15H18NO3 [M+H]+ 260.1287; found
260.1278.
Compound 6b, yellow oil; Rf = 0.47 [petroleum ether/Et2O (50:50)]; ½a D20
ꢁ182
ꢂ
(c 0.4, CHCl3); IR (film) 2986, 2934, 1612, 1372 cmꢁ1 1H NMR (250 MHz,
;
CDCl3) d 7.91 (d, 2H, J = 8.0 Hz, Ar-H), 7.23 (d, 2H, J = 8.0 Hz, Ar-H), 5.49 (d, 1H,
J = 5.5 Hz, H-3), 4.78 (t, 1H, J = 5.5 Hz, H-4), 4.12 (dq, 1H, J = 5.5 7.1 Hz, H-5),
2.40 (s, 3H), 1.53 (d, 3H, J = 7.1 Hz, 5-CH3), 1.40 (s, 3H, CH3), 1.29 (s, 3H, CH3);
13C NMR (62.5 MHz, CDCl3) d 170.1 (C@N), 140.9 (Ar-C), 129.7 (Ar-C), 129.1
(Ar-C), 128.2 (Ar-C), 112.1 (C(CH3)2), 86.4 (C-3), 79.8 (C-4), 67.6 (C-5), 26.9
(C(CH3)2), 26.2 (C(CH3)2), 21.4 (Ar-CH3), 14.2 (5-CH3); ESI-HRMS: calcd for
C15H20NO2 [M+H]+ 246.1494; found 246.1491. Compound 6c, white foam;
18. See Supplementary data.
19. The NaBH4 reduction of such ketimines is usually not selective (see Ref. 9);
thus, we assume that the two possible stereoisomers are formed during the
reaction. Indeed, preliminary NMR analysis of a sample of 4b revealed the
presence of the two possible isomers (two doublets at 1.3 ppm, 2 ꢃ 5-Me).
Rf = 0.32 [petroleum ether/Et2O (50:50)]; ½a D20
ꢁ140 (c 0.32, CHCl3); IR (film)
ꢂ