3742
O. Merino et al. / Tetrahedron Letters 51 (2010) 3738–3742
15. For recent examples: (a) Buzas, A.; Gagosz, F. Synlett 2006, 2727–2730; (b)
Ritter, S.; Horino, Y.; Lex, J.; Schmalz, H.-G. Synlett 2006, 3309–3313; (c)
Robles-Machín, R.; Adrio, J.; Carretero, J. C. J. Org. Chem. 2006, 71, 5023–5026;
(d) Danielec, H.; Klügge, J.; Schlummer, B.; Bach, T. Synthesis 2006, 551–556; (e)
Ritter, S.; Hackelöer, K.; Schmalz, H.-G. Heterocycles 2007, 74, 731–742; (f)
Hashmi, A. S. K.; Salathé, R.; Frey, W. Synlett 2007, 1763–1766; (g) Lee, E.-S.;
Yeom, H.-S.; Hwang, J.-H.; Shin, S. Eur. J. Org. Chem. 2007, 3503–3507; (h)
Gaenzler, F. C.; Smith, M. B. Synlett 2007, 1299–1301; (i) Maggi, R.; Bertolotti,
C.; Orlandini, E.; Oro, C.; Sartori, G.; Selva, M. Tetrahedron Lett. 2007, 48, 2131–
2134; (j) Jiang, H.; Zhao, J.; Wang, A. Synthesis 2008, 763–769; (k) García-
Valverde, M.; Macho, S.; Marcaccini, S.; Rodriguez, T.; Rojo, J.; Torroba, T.
Synlett 2008, 33–36.
16. Martínez, R.; Jiménez-Vázquez, H. A.; Tamariz, J. Tetrahedron 2000, 56, 3857–
3866.
17. Santoyo, B. M.; González-Romero, C.; Merino, O.; Martínez-Palou, R.; Fuentes-
Benites, A.; Jiménez-Vázquez, H. A.; Delgado, F.; Tamariz, J. Eur. J. Org. Chem.
2009, 2505–2518.
Preparation of 7d: A mixture of 6d (0.10 g, 0.42 mmol) and KOH (0.094 g,
1.68 mmol) in a mixture of EtOH/H2O (3:7) (10 mL) was stirred at room
temperature for 3 h. The solvent was removed under vacuum, and the residue
was dissolved with CH2Cl2 (10 mL) and washed with a 5% aqueous solution of
HCl until neutral. The organic layer was dried (Na2SO4), and the solvent
removed under vacuum. The residue was purified by column chromatography
on silica gel (30 g per gram of crude, hexane/EtOAc, 9:1) to give 7d (0.098 g,
47%) as a yellow powder. Rf = 0.36 (hexane/EtOAc, 7:3). Mp 98–100 °C. IR (film):
À1
ꢀ
m
3388, 3298, 1737, 1666, 1592, 1533, 1496, 1398, 1378, 1141, 1089, 821 cm
;
1H NMR (300 MHz, CDCl3): d 1.54 (s, 6H, 2CH3C-5), 2.76 (br s, 1H, OH), 7.25–7.32
(m, 2H, H-Ar), 7.50–7.56 (m, 2H, H-Ar), 8.72 (br s, 1H, NH); 13C NMR (75 MHz,
CDCl3): d 27.9 (2CH3C-2), 74.3 (C-2), 120.8 (2H-Ar), 129.0 (2H-Ar), 129.3 (Ar),
136.1 (Ar), 174.2 (C-1); MS (70 eV): m/z 215 (M++2, 26), 213 (M+, 80), 155 (31),
129 (33), 127 (100), 99 (7), 59 (57). HRMS (EI): calcd for C10H12ClNO2 [M]+
213.0557; found 213.0567.
Preparation of 18c: To a solution of 16a (0.10 g, 0.523 mmol) in dry THF (3 mL),
under N2 atmosphere and at -78 °C, LHMDS (0.105 g, 0.628 mmol) was slowly
added and stirred for 1 h. Then, at the same temperature, 17c (0.094 g,
0.628 mmol) in dry THF (2 mL), was added dropwise and the mixture was
stirred for 1 h. The mixture was diluted with CH2Cl2 (10 mL), and the organic
layer was washed with a saturated aqueous solution of NH4Cl (3 Â 10 mL) until
neutral. The organic layer was dried (Na2SO4), and the solvent removed under
vacuum. The residue was purified by column chromatography on silica gel (30 g
per gram of crude, hexane/EtOAc, 98:2) to give 18c (0.094 g, 69%) as a white
ꢀ
18. Typical experimental procedures: Preparation of 5d: A mixture of 3b (0.10 g,
0.98 mmol) and 4d (0.18 g, 1.18 mmol) was placed in a threaded ACE glass
pressure tube with a sealed Teflon screw cap under N2. The mixture was
stirred and heated at 130 °C for 24 h. The mixture was diluted with CH2Cl2
(10 mL) and filtered, then the solvent was removed under vacuum. The
residue was purified by column chromatography on silica gel (30 g per gram
of crude, hexane/EtOAc, 9:1) to give 5d (0.20 g, 88%) as colorless crystals.
ꢀ
Rf = 0.65 (hexane/EtOAc, 7:3). Mp 127–129 °C. IR (film):
m
1764, 1681, 1639,
powder. Rf = 0.70 (hexane/EtOAc, 7:3). Mp 74–75 °C. IR (film):
m
1814, 1746,
1499, 1407, 1303, 1189, 1089, 1078, 824 cmÀ1
;
1H NMR (300 MHz, CDCl3): d
1502, 1402, 1172, 767 cmÀ1 1H NMR (500 MHz, CDCl3): d 1.68 (s, 3H, CH3C-5),
;
1.63 (s, 6H, 2CH3C-5), 4.07 (d, J = 2.9 Hz, 1H, CH2@), 4.14 (d, J = 2.9 Hz, 1H,
CH2@), 7.27–7.33 (m, 2H, H-Ar), 7.43–7.48 (m, 2H, H-Ar); 13C NMR (75 MHz,
CDCl3): d 28.0 (2CH3C-5), 81.4 (CH2@), 82.6 (C-5), 128.3 (2H-Ar), 129.8 (2H-
Ar), 132.5 (Ar), 134.0 (Ar), 151.4 (C-4), 154.2 (C-2); MS (70 eV): m/z 239
(M++2, 17), 237 (M+, 56), 192 (36), 178 (82), 158 (67), 138 (100), 111 (45),
75 (41), 56 (71). HRMS (EI): calcd for C12H12ClNO2 [M]+ 237.0557; found
237.0562.
1.68 (d, J = 1.0 Hz, 3H, CH3C@), 1.74 (d, J = 1.0 Hz, 3H, CH3C@), 2.63 (br dd,
J = 14.5, 7.5 Hz, 1H, CH2CH@), 2.69 (br dd, J = 14.5, 8.0 Hz, 1H, CH2CH@), 5.12–
5.17 (m, 1H, CH@), 7.33–7.36 (m, 2H, H-Ar), 7.39–7.43 (m, 1H, H-Ar), 7.46–7.51
(m, 2H, H-Ar); 13C NMR (75.4 MHz, CDCl3): d 18.1 (CH3CH@), 22.0 (CH3C-5), 25.9
(CH3CH@), 35.9 (CH2CH@), 86.3 (C-5), 114.5 (CH@), 125.6 (2H-Ar), 128.8 (H-Ar),
129.3 (2H-Ar), 131.0 (Ar), 139.4 (Me2C@), 153.6 (C-2), 174.4 (C-4). HRMS (FAB):
calcd for C15H17NO3 [M+1]+ 260.1287; found 260.1290.
Preparation of 6d: A mixture of 5d (0.10 g, 0.42 mmol) and MCPBA (0.146 g,
0.84 mmol) in CH2Cl2 (6 mL) was stirred at room temperature for 12 h. Then,
at the same temperature, MCPBA (0.146 g, 0.84 mmol) was added and the
mixture stirred for 12 h. The mixture was diluted with CH2Cl2 (10 mL) and
washed with an aqueous saturated solution of NaHCO3 until neutral. The
organic layer was dried (Na2SO4), and the solvent removed under vacuum.
The residue was purified by column chromatography on silica gel (30 g per
gram of crude, hexane/EtOAc, 9:1) to give 6d (0.098 g, 97%) as colorless
ꢀ
19. Benavides, A.; Martínez, R.; Jiménez-Vázquez, H. A.; Delgado, F.; Tamariz, J.
Heterocycles 2001, 55, 469–485.
20. (a) Hudlicky, M. Oxidations in Organic Chemistry; American Chemical Society:
Washington, DC, 1990; (b) Pitacco, G.; Valentin, E. Oxidation and Reduction of
Enamines. In The Chemistry of Enamines; Rappoport, Z., Ed.; Wiley: Chichester,
1994; Vol. 2, pp 935–942.
21. CCDC-743102 (for 6a), -743103 (for 6d), -743104 (for 7a), -743105 (for 16a),
and -743106 (for 18b) contain the supplementary crystallographic data for this
paper. These data can be obtained free of charge from The Cambridge
22. Orduña, A.; Zepeda, L. G.; Tamariz, J. Synthesis 1993, 375–377.
23. González-Romero, C.; Bernal, P.; Jiménez, F.; Cruz, M. C.; Fuentes-Benites, A.;
Benavides, A.; Bautista, R.; Tamariz, J. Pure Appl. Chem. 2007, 79, 181–191.
24. Grover, P. T.; Bhongle, N. N.; Wald, S. A.; Sananayake, C. H. J. Org. Chem. 2000,
65, 6283–6287.
crystals. Rf = 0.68 (hexane/EtOAc, 7:3). Mp 118–119.5 °C. IR (film):
m
1820,
1743, 1500, 1421, 1283, 1239, 1177, 1091, 827 cmÀ1
;
1H NMR (300 MHz,
CDCl3): d 1.68 (s, 6H, 2CH3C-5), 7.38–7.48 (m, 4H, H-Ar); 13C NMR (75 MHz,
CDCl3): d 23.7 (2CH3C-5), 83.5 (C-5), 126.6 (2H-Ar), 129.3 (2H-Ar), 129.4
(Ar), 134.5 (Ar), 152.8 (C-2), 174.5 (C-4); MS (70 eV): m/z 239 (M+, 9), 169
(24), 167 (61), 152 (100), 125 (17), 90 (34), 69 (21), 63 (21). HRMS (EI):
calcd for C11H10ClNO3 [M]+ 239.0349; found 239.0352.