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K. H. Kim et al. / Tetrahedron Letters 53 (2012) 5088–5093
(20 mL ꢀ 3), and the organic layer was dried over MgSO4. After the removal of
References and notes
solvent and column chromatographic purification process (hexanes/EtOAc,
5:1) compound 3a was isolated as a pale yellow solid, 117 mg (87%). Other
compounds were synthesized similarly, and the selected spectroscopic data of
compounds 3a–e, 4b, and 4g are as follows.
1. Nahm, S.; Weinreb, S. M. Tetrahedron Lett. 1981, 22, 3815–3818.
2. For the synthetic applications of
a,b-unsaturated Weinreb amides, see: (a)
Marrec, O.; Borrini, J.; Billard, T.; Langlois, B. R. Synlett 2009, 1241–1244; (b)
Bennani, Y. L.; Sharpless, K. B. Tetrahedron Lett. 1993, 34, 2079–2082; (c)
Rodriques, K. E. Tetrahedron Lett. 1991, 32, 1275–1278; (d) Nuzillard, J.-M.;
Boumendjel, A.; Massiot, G. Tetrahedron Lett. 1989, 30, 3779–3780; (e) Evans, D.
A.; Kaldor, S. W.; Jones, T. K.; Clardy, J.; Stout, T. J. J. Am. Chem. Soc. 1990, 112,
7001–7031; (f) Davies, S. G.; Iwamoto, K.; Smethurst, C. A. P.; Smith, A. D.;
Rodriguez-Solla, H. Synlett 2002, 1146–1148; (g) Burke, A. J.; Davies, S. G.;
Garner, A. C.; McCarthy, T. D.; Roberts, P. M.; Smith, A. D.; Rodriguez-Solla, H.;
Vickers, R. L. Org. Biomol. Chem. 2004, 2, 1387–1394; (h) Corminboeuf, O.;
Renaud, P. Org. Lett. 2002, 4, 1735–1738; (i) Shintani, R.; Kimura, T.; Hayashi, T.
Chem. Commun. 2005, 3213–3214.
Compound 3a: 87%; pale yellow solid, mp 76–77 °C; IR (KBr) 1654, 1616, 1380,
1178 cmꢁ1 1H NMR (CDCl3, 300 MHz) d 3.15 (s, 3H), 3.70 (s, 3H), 6.70 (br s,
;
1H), 7.21–7.27 (m, 2H), 7.28–7.38 (m, 8H); 13C NMR (CDCl3, 75 MHz) d 32.31,
61.60, 117.38, 127.85, 128.00, 128.18, 128.20, 128.75, 129.17, 139.10, 141.56,
153.10, 167.24; ESIMS m/z 268 [M+1]+. Anal. Calcd for C17H17NO2: C, 76.38; H,
6.41; N, 5.24. Found: C, 76.69; H, 6.56; N, 5.11.Compound 3b: 68%; pale yellow
oil; IR (film) 1654, 1617, 1378, 1178 cmꢁ1 1H NMR (CDCl3, 300 MHz) d 2.02 (s,
;
3H), 2.33 (s, 3H), 3.19 (s, 3H), 3.67 (s, 3H), 6.29 (br s, 1H), 7.01–7.09 (m, 3H), 7.20–
7.30 (m, 5H); 13C NMR (CDCl3, 75 MHz) d 19.78, 20.84, 32.40, 61.69, 120.32,
127.88, 128.08, 128.72, 128.76, 130.30, 130.39, 132.91, 135.08, 138.99, 142.04,
152.16, 167.99; ESIMS m/z 296 [M+1]+. Anal. Calcd for C19H21NO2: C, 77.26; H,
7.17; N, 4.74. Found: C, 77.17; H, 7.34; N, 4.61.
3. (a) For the biological activity of a,b-unsaturated Weinreb amides, see: Li, Z.; Liu,
C.; Liu, W. USP 6020,332, 2000 (Chem. Abstr. 2000, 132, 118764).; (b) Li, Z.; Liu, C.;
Liu, W. CN 1167568, 1997 (Chem. Abstr. 2000, 132, 60481).; (c) Li, Z.; Liu, C.; Liu,
W. EP 860438A1, 1998 (Chem. Abstr. 1998, 129, 189128).; (d) Jan, V.; Gunther, H.;
Peter, B.; Burkhard, S. EP 601477A1, 1994 (Chem. Abstr. 1994, 121, 108248).
Compound 3c: 69%; pale yellow oil; IR (film) 1655, 1614, 1597, 1376, 1176 cmꢁ1
;
1H NMR (CDCl3, 300 MHz) d 2.28 (s, 6H), 3.14 (s, 3H), 3.70 (s, 3H), 6.65 (br s, 1H),
6.80–7.02 (m, 3H), 7.18–7.28 (m, 2H), 7.29–7.38 (m, 3H); 13C NMR (CDCl3,
125 MHz) d 21.22, 32.36, 61.61, 117.26, 126.12, 127.85, 127.96, 129.20, 130.54,
137.76, 139.37, 141.58, 153.70, 167.41; ESIMS m/z 296 [M+1]+. Anal. Calcd for
4. For the synthesis of Weinreb amides from carboxylic acids including
a,b-
unsaturated derivatives, see: (a) Niu, T.; Zhang, W.; Huang, D.; Xu, C.; Wang, H.;
Hu, Y. Org. Lett. 2009, 11, 4474–4477; (b) Kumar, A.; Akula, H. K.; Lakshman, M.
K. Eur. J. Org. Chem. 2010, 2709–2715; (c) Kim, J.-G.; Jang, D. O. Bull. Korean
Chem. Soc. 2010, 31, 171–173; (d) Hioki, K.; Kobayashi, H.; Ohkihara, R.; Tani, S.;
Kunishima, M. Chem. Pharm. Bull. 2004, 52, 470–472; (e) Williams, J. M.; Jobson,
R. B.; Yasuda, N.; Marchesini, G.; Dolling, U.-H.; Grabowski, E. J. J. Tetrahedron
Lett. 1995, 36, 5461–5464.
C
19H21NO2: C, 77.26; H, 7.17; N, 4.74. Found: C, 77.57; H, 7.40; N, 4.83.
Compound 3d: 82%; pale yellow oil; IR (film) 1654, 1610, 1376, 1175 cmꢁ1
;
1H
NMR (CDCl3, 300 MHz) d 2.15 (s, 3H), 2.19 (s, 3H), 3.06 (s, 3H), 3.62 (s, 3H), 6.60
(br s, 1H), 6.86–7.06 (m, 3H), 7.10–7.19 (m, 2H), 7.20–7.31 (m, 3H); 13C NMR
(CDCl3, 125 MHz) d 19.52, 19.78, 32.35, 61.65, 116.51, 125.85, 127.85, 127.94,
129.22, 129.36, 129.56, 136.48, 137.70, 139.16, 139.41, 153.50, 167.35; ESIMS m/
z 296 [M+1]+. Anal. Calcd for C19H21NO2: C, 77.26; H, 7.17; N, 4.74. Found: C,
77.32; H, 7.02; N, 4.63.
5. For the synthesis of a,b-unsaturated Weinreb amides via Horner–Wadsworth–
Emmons and Wittig type reactions, see: (a) Ando, K. Synlett 2001, 1272–1274;
(b) Ando, K.; Nagaya, S.; Tarumi, Y. Tetrahedron Lett. 2009, 50, 5689–5691; (c)
Kojima, S.; Hidaka, T.; Yamakawa, A. Chem. Lett. 2005, 34, 470–471; (d) Kojima,
S.; Hidaka, T.; Ohba, Y. Heteroatom Chem. 2004, 15, 515–523; (e) Fortin, S.;
Dupont, F.; Deslongchamps, P. J. Org. Chem. 2002, 67, 5437–5439; (f) Piva, O.;
Comesse, S. Eur. J. Org. Chem. 2000, 2417–2424; (g) Blackburn, L.; Kanno, H.;
Taylor, R. J. K. Tetrahedron Lett. 2003, 44, 115–118; (h) Fang, F.; Li, Y.; Tian, S.-K.
Eur. J. Org. Chem. 2011, 1084–1091.
Compound 3e: 80%; pale yellow oil; IR (film) 1653, 1616, 1468, 1370, 1130 cmꢁ1
;
1H NMR (CDCl3, 300 MHz) d 3.15 (s, 3H), 3.71 (s, 3H), 6.67 (br s, 1H), 7.13 (dd,
J = 8.4 and 2.1 Hz, 1H), 7.17–7.24 (m, 2H), 7.33–7.42 (m, 5H); 13C NMR (CDCl3,
75 MHz) d 32.26, 61.82, 118.91, 127.46, 128.19, 128.52, 129.12, 129.91, 130.23,
132.58, 132.90, 138.06, 141.60, 150.46, 166.76; ESIMS m/z 336 [M+1]+, 338
[M+3]+. Anal. Calcd for C17H15Cl2NO2: C, 60.73; H, 4.50; N, 4.17. Found: C, 60.86;
H, 4.85; N, 4.14.
Compound 4b: 16%; pale yellow solid, mp 116–117 °C; IR (KBr) 1658, 1614, 1376,
1176 cmꢁ1;1HNMR (CDCl3, 300 MHz) d2.05(s, 3H), 2.30 (s, 3H), 3.15(s, 3H), 3.73
(s, 3H), 6.88 (br s, 1H), 6.92 (br s, 1H), 7.02–7.12 (m, 2H), 7.26–7.36 (m, 5H);
ESIMS m/z 296 [M+1]+.
Compound 4g: 20%; white solid, mp 110–111 °C; IR (KBr) 1663, 1598, 1380,
1174 cmꢁ1;1HNMR(CDCl3, 300 MHz)d3.09 (s, 3H), 3.54 (s, 3H), 3.76(s, 2H), 6.98
(s, 1H), 7.15–7.23 (m, 2H), 7.24–7.33 (m, 6H), 7.40–7.46 (m, 2H); 13C NMR (CDCl3,
75 MHz) d 32.43, 34.40, 61.20, 126.28, 127.01, 127.40, 128.30, 128.42, 128.72,
131.30, 135.46, 137.74, 142.25, 172.36; ESIMS m/z 282 [M+1]+. Anal. Calcd for
6. For the synthesis of
a,b-unsaturated Weinreb amides via the Julia and Julia-
Kocienski olefination protocols, see: (a) Manjunath, B. N.; Sane, N. P.; Aidhen, I.
S. Eur. J. Org. Chem. 2006, 2851–2855; (b) Alonso, D. A.; Fuensanta, M.; Gomez-
Bengoa, E.; Najera, C. Adv. Synth. Catal. 2008, 350, 1823–1829; (c) Alonso, D. A.;
Fuensanta, M.; Gomez-Bengoa, E.; Najera, C. Eur. J. Org. Chem. 2008, 2915–
2922; (d) Ghosh, A. K.; Banerjee, S.; Sinha, S.; Kang, S. B.; Zajc, B. J. Org. Chem.
2009, 74, 3689–3697; (e) Beney, C.; Boumendjel, A.; Mariotte, A.-M.
Tetrahedron Lett. 1988, 39, 5779–5780.
7. For the other synthesis of a,b-unsaturated Weinreb amides, see: (a) Vedrenne,
C
18H19NO2: C, 76.84; H, 6.81; N, 4.98. Found: C, 76.69; H, 6.92; N, 4.83.
E.; Dupont, H.; Oualef, S.; Elkaim, L.; Grimaud, L. Synlett 2005, 670–672; (b) Lu,
B.-L.; Shi, M. Chem. Eur. J. 2011, 17, 9070–9075.
8. Krishnamoorthy, R.; Lam, S. Q.; Manley, C. M.; Herr, R. J. J. Org. Chem. 2010, 75,
1251–1258.
Typical procedure for the synthesis of 3a with iodobenzene: A stirred solution of 2a
(96 mg, 0.5 mmol), iodobenzene (205 mg, 1.0 mmol), and Pd(OAc)2 (5.6 mg,
5 mol %) in triethylamine (0.7 mL, 5.0 mmol) was heated to 100 °C for 16 h under
nitrogen atmosphere. After the aqueous extractive workup and column
chromatographic purification process (hexanes/EtOAc, 5:1) compound 3a was
9. For selected oxidative Heck arylation with arenes, see: (a) Bras, J. L.; Muzart, J.
Chem. Rev. 2011, 111, 1170–1214; (b) Yeung, C. S.; Dong, V. M. Chem. Rev. 2011,
111, 1215–1292; (c) Rossi, R.; Bellina, F.; Lessi, M. Synthesis 2010, 4131–4153;
(d) Karimi, B.; Behzadnia, H.; Elhamifar, D.; Akhavan, P. F.; Esfahani, F. K.;
Zamani, A. Synthesis 2010, 1399–1427; (e) Zhang, Y.-H.; Shi, B.-F.; Yu, J.-Q. J. Am.
Chem. Soc. 2009, 131, 5072–5074; (f) Yokota, T.; Tani, M.; Sakaguchi, S.; Ishii, Y.
J. Am. Chem. Soc. 2003, 125, 1476–1477; (g) Jia, C.; Lu, W.; Kitamura, T.;
Fujiwara, Y. Org. Lett. 1999, 1, 2097–2100; (h) Kubota, A.; Emmert, M. H.;
Sanford, M. S. Org. Lett. 2012, 14, 1760–1763; (i) Nishikata, T.; Lipshutz, B. H.
Org. Lett. 2010, 12, 1972–1975; (j) Pan, D.; Yu, M.; Chen, W.; Jiao, N. Chem. Asian
J. 2010, 5, 1090–1093; (k) Li, Z.; Zhang, Y.; Liu, Z.-Q. Org. Lett. 2012, 14, 74–77;
(l) Shang, X.; Xiong, Y.; Zhang, Y.; Zhang, L.; Liu, Z. Synlett 2012, 259–262; (m)
Zhang, Y.; Li, Z.; Liu, Z.-Q. Org. Lett. 2012, 14, 226–229.
10. For our recent papers, see: (a) Kim, K. H.; Lee, H. S.; Kim, J. N. Tetrahedron Lett.
2011, 52, 6228–6233; (b) Kim, K. H.; Lee, H. S.; Kim, S. H.; Kim, J. N. Tetrahedron
Lett. 2012, 53, 1323–1327; (c) Kim, K. H.; Lee, H. S.; Kim, S. H.; Kim, J. N.
Tetrahedron Lett. 2012, 53, 2761–2764. and further references cited therein; The
condition employing PivOH as a proton shuttle during the aryl C–H bond
activation was originally developed by Fagnou and applied extensively for the C–
H bond activation of arenes, see: (d) Lafrance, M.; Fagnou, K. J. Am. Chem. Soc.
2006, 128, 16496–16497; (e) Stuart, D. R.; Villemure, E.; Fagnou, K. J. Am. Chem.
Soc. 2007, 129, 12072–12073; (f) Stuart, D. R.; Fagnou, K. Science 2007, 316, 1172–
1175; (g) Liegault, B.; Lee, D.; Huestis, M. P.; Stuart, D. R.; Fagnou, K. J. Org. Chem.
2008, 73, 5022–5028; (h) Gorelsky, S. I.; Lapointe, D.; Fagnou, K. J. Org. Chem.
2012, 77, 658–668; (i) Potavathri, S.; Pereira, K. C.; Gorelsky, S. I.; Pike, A.; LeBris,
A. P.; DeBoef, B. J. Am. Chem. Soc. 2010, 132, 14676–14681; (j) Potavathri, S.;
Kantak, A.; DeBoef, B. Chem. Commun. 2011, 47, 4679–4681; (k) Miyasaka, M.;
Hirano, K.; Satoh, T.; Miura, M. J. Org. Chem. 2010, 75, 5421–5424; (l)
Baghbanzadeh, M.; Pilger, C.; Kappe, C. O. J. Org. Chem. 2011, 76, 8138–8142.
11. Typical procedure for the synthesis of 3a with benzene: A stirred solution of 2a
(96 mg, 0.5 mmol), Pd(TFA)2 (8.3 mg, 5 mol %), AgOAc (252 mg, 1.5 mmol), and
PivOH (308 mg, 3.0 mmol) in benzene (2.7 mL, 30 mmol) was heated to reflux
under nitrogen atmosphere for 20 h. After cooling to room temperature, the
reaction mixture was filtered over a pad of Celite and washed with CH2Cl2
(100 mL). The filtrates were washed with a saturated solution of NaHCO3
obtained as
a pale yellow solid, 126 mg (94%). Other compounds were
synthesized similarly, and the spectroscopic data of compounds 3f, 3h–j, and
4i are as follows.
Compound 3f: 80%; colorless oil; IR (film) 1653, 1609, 1378, 1178, 1114 cmꢁ1 1H
;
NMR (CDCl3, 300 MHz) d 2.28 (s, 3H), 3.06 (s, 3H), 3.62 (s, 3H), 6.61 (br s, 1H),
7.02–7.08 (m, 2H), 7.09–7.19 (m, 4H), 7.23–7.30 (m, 3H); 13C NMR (CDCl3,
75 MHz) d 21.15, 32.31, 61.65, 116.45, 127.85, 127.96, 128.16, 128.96, 129.18,
138.66, 138.96, 139.31, 153.42, 167.40; ESIMS m/z 282 [M+1]+. Anal. Calcd for
C
18H19NO2: C, 76.84; H, 6.81; N, 4.98. Found: C, 77.04; H, 7.06; N, 4.77.
Compound 3h: 72%; pale yellow oil; IR (film) 1654, 1619, 1379, 1178, 1115 cmꢁ1
;
1H NMR (CDCl3, 300 MHz) d 2.07 (s, 3H), 3.19 (s, 3H), 3.66 (s, 3H), 6.30 (br s, 1H),
7.12–7.31 (m, 9H); 13C NMR (CDCl3, 75 MHz) d 20.25, 32.28, 61.65, 120.48,
125.63, 127.85, 127.95, 128.07, 128.71, 129.62, 130.46, 136.06, 138.89, 142.15,
151.86, 167.91; ESIMS m/z 282 [M+1]+. Anal. Calcd for C18H19NO2: C, 76.84; H,
6.81; N, 4.98. Found: C, 76.91; H, 6.96; N, 4.69.
Compound 3i: 88%; pale yellow oil; IR (film) 1653, 1603, 1510, 1379, 1248, 1179,
1031 cmꢁ1 1H NMR (DMSO-d6, 300 MHz) d 3.05 (s, 3H), 3.67 (s, 3H), 3.76 (s, 3H),
;
6.63 (br s, 1H), 6.93 (d, J = 9.0 Hz, 2H), 7.08–7.15 (m, 2H), 7.20 (d, J = 9.0 Hz, 2H),
7.29–7.40 (m, 3H); 13C NMR (DMSO-d6, 75 MHz) d 32.18, 55.21, 61.15, 113.90,
116.96, 127.72, 127.85, 129.05, 129.24, 133.20, 139.25, 150.29, 159.87, 166.55;
ESIMS m/z 298 [M+1]+. Anal. Calcd for C18H19NO3: C, 72.71; H, 6.44; N, 4.71.
Found: C, 72.98; H, 6.71; N, 4.74.
Compound 3j: 89%; pale yellow oil; IR (film) 1715, 1654, 1608, 1274, 1102 cmꢁ1
;
1H NMR (CDCl3, 500 MHz) d 1.32 (t, J = 7.0 Hz, 3H), 3.11 (s, 3H), 3.66 (s, 3H), 4.31
(q, J = 7.0 Hz, 2H), 6.69 (br s, 1H), 7.12–7.18 (m, 2H), 7.26–7.29 (m, 3H), 7.30 (d,
J = 8.0 Hz, 2H), 7.93 (d, J = 8.0 Hz, 2H); 13C NMR (CDCl3, 125 MHz) d 14.25, 32.20,
61.02, 61.81, 119.14, 128.05, 128.17, 128.27, 129.15, 129.47, 130.51, 138.55,
145.92, 151.88, 166.09, 167.01; ESIMS m/z 340 [M+1]+. Anal. Calcd for
C20H21NO4: C, 70.78; H, 6.24; N, 4.13. Found: C, 70.86; H, 6.44; N, 4.04.
Compound 4i: 82%; pale yellow oil; IR (film) 1651, 1573, 1510, 1378, ‘1247,
1175 cmꢁ1;1HNMR(CDCl3, 500 MHz)d3.10 (s, 3H), 3.64 (s, 3H), 3.74(s, 3H), 6.54
(br s, 1H), 6.80 (d, J = 8.5 Hz, 2H), 7.07–7.13 (m, 2H), 7.21–7.31 (m, 5H); 13C NMR
(CDCl3, 125 MHz) d 32.47, 55.10, 61.78, 113.29, 116.74, 128.19, 128.46, 128.76,