An expedient synthesis of poly-substituted 1-arylisoquinolines from δ-ketonitriles via indium-mediated Barbier reaction protocol

Tetrahedron Letters

Volumn 50, Issue 47, 2009, Pages 6476-6479

  Kim, Sung Hwan ^a   Lee, Hyun Seung ^a   Kim, Ko Hoon ^a   Kim, Jae Nyoung ^a  

^a Chonnam National University   (South Korea)

Author keywords

Barbier reaction; Indium; Isoquinolines; Ketonitriles

Indexed keywords

DELTA KETONITRILE; INDIUM; ISOQUINOLINE DERIVATIVE; NITRILE; UNCLASSIFIED DRUG;

ARTICLE; BARBIER REACTION; CHEMICAL REACTION; SYNTHESIS;

EID: 73049113992     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2009.09.013     Document Type: Article

References (38)

1. For the general review on indium-mediated reactions, see: (a) Auge, J.; Lubin-Germain, N.; Uziel, J. Synthesis 2007, 1739-1764;
2. (b) Li, C.-J.; Chan, T.-H. Tetrahedron 1999, 55, 11149-11176;
3. (c) Pae, A. N.; Cho, Y. S. Curr. Org. Chem. 2002, 6, 715-737.
4. For the indium-mediated Barbier type allylation of imine, acylimine, sulfonimine and related compounds, see: (a) Vilaivan, T.; Winotapan, C.; Banphavichit, V.; Shinada, T.; Ohfune, Y. J. Org. Chem. 2005, 70, 3464-3471;
5. (b) Schneider, U.; Chen, I.-H.; Kobayashi, S. Org. Lett. 2008, 10, 737-740;
6. (c) Kumar, H. M. S.; Anjaneyulu, S.; Reddy, E. J.; Yadav, J. S. Tetrahedron Lett. 2000, 41, 9311-9314;
7. (d) Piao, X.; Jung, J.-K.; Kang, H.-Y. Bull. Korean Chem. Soc. 2007, 28, 139-142;
8. (e) Ritson, D. J.; Cox, R.J.; Berge, J. Org. Biomol. Chem. 2004, 2, 1921-1933;
9. (f) Lu, W.; Chan, T. H. J. Org. Chem. 2000, 65, 8589-8594;
10. (g) Ranu, B. C.; Das, A. Tetrahedron Lett. 2004, 45, 6875-6877.
11. (a) Fujiwara, N.; Yamamoto, Y. Tetrahedron Lett. 1998, 39, 4729-4732;
12. (b) Fujiwara, N.; Yamamoto, Y. J. Org. Chem. 1999, 64, 4095-4101.
13. (a) Kim, S. H.; Lee, H. S.; Kim, K. H.; Kim, J. N. Tetrahedron Lett. 2009, 50, 1696-1698;
14. (b) Kim, S. H.; Kim, S. H.; Lee, K. Y.; Kim, J. N. Tetrahedron Lett. 2009, 50, 5744-5747.
15. For the synthesis and biological activities of isoquinoline-containing compounds, see: (a) Bentley, K. W. In The Isoquinoline Alkaloids; Hardwood Academic: Amsterdam, 1998; Vol. 1;
16. (b) Mach, U. R.; Hackling, A. E.; Perachon, S.; Ferry, S.; Wermuth, C. G.; Schwartz, J.-C.; Sokoloff, P.; Stark, H. ChemBioChem 2004, 5, 508-518;
17. (c) Muscarella, D. E.; O'Brien, K. A.; Lemley, A. T.; Bloom, S. E. Toxicol. Sci. 2003, 74, 66-73;
18. 5c
19. see: (e) Scarf, A. M.; Ittner, L. M.; Kassiou, M. J. Med. Chem. 2009, 52, 581-592;
20. (f) Yu, W.; Wang, E.; Voll, R. J.; Miller, A. H.; Goodman, M. M. Bioorg. Med. Chem. 2008, 16, 6145-6155.
21. For the synthesis and biological activities of isoquinoline derivatives, see: (a) Huo, Z.; Yamamoto, Y. Tetrahedron Lett. 2009, 50, 3651-3653;
22. (b) Fischer, D.; Tomeba, H.; Pahadi, N. K.; Patil, N. T.; Yamamoto, Y. Angew. Chem., Int. Ed. 2007, 46, 4764-4766;
23. (c) Hui, B. W.-Q.; Chiba, S. Org. Lett. 2009, 11, 729-732;
24. (d) Niu, Y.-N.; Yan, Z.-Y.; Gao, G.-L.; Wang, H.-L.; Shu, X.-Z.; Ji, K.-G.; Liang, Y.-M. J. Org. Chem. 2009, 74, 2893-2896;
25. (e) Gerfaud, T.; Neuville, L.; Zhu, J. Angew. Chem., Int. Ed. 2009, 48, 572-577;
26. (f) Hwang, S.; Lee, Y.; Lee, P. H.; Shin, S. Tetrahedron Lett. 2009, 50, 2305-2308;
27. (g) Movassaghi, M.; Hill, M. D. Org. Lett. 2008, 10, 3485-3488;
28. (h) Blackburn, T.; Ramtohul, Y. K. Synlett 2008, 1159-1164;
29. (i) Alonso, R.; Campos, P. J.; Garcia, B.; Rodriguez, M. A. Org. Lett. 2006, 8, 3521-3523;
30. (j) Xiang, Z.; Luo, T.; Lu, K.; Cui, J.; Shi, X.; Fathi, R.; Chen, J.; Yang, Z. Org. Lett. 2004, 6, 3155-3158;
31. (k) Ichikawa, J.; Wada, Y.; Miyazaki, H.; Mori, T.; Kuroki, H. Org. Lett. 2003, 5, 1455-1458;
32. (l) Ishii, H.; Imai, Y.; Hirano, T.; Maki, S.; Niwa, H.; Ohashi, M. Tetrahedron Lett. 2000, 41, 6467-6471;
33. (m) Roesch, K. R.; Larock, R. C. Org. Lett. 1999, 1, 553-556;
34. (n) Roesch, K. R.; Larock, R. C. J. Org. Chem. 2002, 67, 86-94.
35. Typical procedure for the synthesis ofcompounds 3a and 4a: A stirred mixture of 2-fluorobenzophenone (1a, 200 mg, 1.0mmol), methyl cyanoacetate (2a, 198 mg, 2.0 mmol), Cs2CO3 (751 mg, 2.0 mmol) in DMSO (2 mL) was h eated to 130-140 °C for 5 h. After the usual aqueous workup and column chromatographic purification process (hexanes/EtOAc/CH2Cl2, 16:2:1) compound 3a was isolated as a pale yellow solid, 176 mg (63%). A stirred mixture of compound 3a (140 mg, 0.50 mmol), allyl bromide (121 mg, 1.0mmol) and indium powder (57 mg, 0.5 mmol) in THF (1 mL) was heated to reflux for 30 min. After the usual aqueous workup and column chromatographic purification process (hexanes/CH2Cl 2/EtOAc, 16:1:1) compound 4a was isolated as pale yellow oil, 113 mg (74%). Other compounds were synthesized similarly and the selected spectroscopic data of 3a, 4a, 4e, 4g, 5a, 5b, 9a and 11 are as follows.Compound 3a: 63%; pale yellow solid, mp 91 92 °C; IR (KBr) 2252, 1752, 1658, 1448,1272 cm-1; 1H NMR (CDCl3, 300 MHz) δ 3.72 (s, 3H), 5.71 (s, 1H), 7.44-7.52 (m, 4H), 7.59-7.66 (m, 2H), 7.77-7.81 (m, 3H); 13C NMR (CD13, 75 MHz) δ 39.92, 53.78, 115.64, 128.42 (2C), 129.96, 129.99,130.35, 131.27, 131.96, 133.33, 136.66, 137.18, 165.26, 197.31; ESIMS m/z 280 (M++1).Compound 4a: 74%; pale yellow oil; IR (film) 2950,1726,1553, 1254, 1214 cm-1; 1H NM (CDCl3, 300 MHz) δ 3.85 (dt, J = 6.6 and 1.5 Hz, 2H), 4.05 (s, 3H), 5.08-5.21 (m, 2H), 6.08-6.22 (m, 1H), 7.46-7.55 (m, 4H), 7.65-7.72 (m, 3H), 7.89-7.92 (m, 1H), 8.05-8.08 (m, 1H); 13C NMR (CDC13, 75 MHz) δ 41.19, 52.39, 116.29, 122.33, 124.08, 124.71, 126.81, 127.77, 128.32, 128.84, 129.95, 130.84, 134.32, 135.70, 139.07, 150.02, 161.93, 168.94; ESIMS m/z 304 (M++1). Anal. Calcd for C20H17NO2: C, 79.19; H, 5.65; N, 4.62. Found: C, 79.44; H, 5.89; N, 4.37.Compound 4e: 76%; white solid, mp 87-88 °C; IR (KBr) 2951, 1726, 1556, 1250, 1214 cm-1; 1H NMR (CDCL3, 300 MHz) δ 3.84 (dt, J = 6.6 and 1.5 Hz, 2H), 4.06 (s, 3H), 5.08-5.20 (m, 2H), 6.07-6.20 (m, 1H), 7.45-7.57 (m,4H), 7.63-7.72 (m, 3H), 7.95 (dd, J =9.3 and 5.1Hz, 1H); 13C NMR (CDCl3, 75 MHz) δ 41.07, 52.50, 111.16 (JC-F = 22.1 Hz), 116.40, 121.29 (JC-F = 25.2 Hz), 122.12, 125.65 (Jc-f = 8.0 Hz), 127.01 (Jc-f = 8.3 Hz), 128.52, 129.10, 129.75, 131.43, 135.59, 138.64, 149.80 (Jc-f = 2.6 Hz), 160.54 (Jc-f = 247.3 Hz), 161.31 (Jc-f = 5.5Hz), 168.65; ESIMS m/z 322 (M++1). Anal. Calcd for C20H16FNO2:C, 74.75; H, 5.02; N, 4.36. Found: C, 74.91; H, 4.96; N, 4.22.Compound 4g: 66%; pale yellow oil; IR (film) 2949, 1727, 1552, 1252, 1214 cm-1; 1H NMR (CD C13, 300 MHz) δ 1.79 (s, 3H), 3.84 (s, 2H), 4.03 (s, 3H), 4.70-4.71 (m, 1H), 4.85-4.86 (m, 1H), 7.45-7.55 (m, 4H), 7.65-7.72 (m, 3H), 7.89-7.92 (m, 1H), 8.06-8.10 (m, 1H); 13C NMR (CDCl3, 75 MHz) δ 22.62, 44.69, 52.37, 112.37, 122.86, 124.14, 124.70, 126.81, 127.72, 128.32, 128.81, 129.97, 130.77, 134.30, 139.10, 143.36, 149.86, 161.59, 169.00; ESIMS m/z 318 (M++1).
36. Starting material 3d (R1 = R3 = H, Ar = Ph) was prepared from 2-methylbenzophenone by successive bromination (NBS, AIBN, CCl4, reflux, 2 h, 80%) and displacement reaction with cyanide (KCN, DMF, rt, 1 h, 61%).
37. Compound 3g was prepared from o-toluic acid via three steps: (i) H2SO4 (cat)/ EtOH (reflux, 7 h, 96%), (ii) NBS/AIBN (cat)/CCL4, (reflux, 4 h, 81%), and (iii) KCN/ H2O/EtOH (reflux, 4 h, 74%). Compound 3h was prepared from homophthalic acid via three steps: (i) H2SO4 (cat)/MeOH (reflux, 7 h, 94%), (ii) NBS/AIBN (cat)/ CCl4 (reflux, 4 h, 79%), and (iii) KCN/DMF (rt, 1 h, 69%). Compounds 3i and 3k were prepared from 2-fluorobenzoni trile via a SNAr reaction with methyl cyanoacetate and dimethyl malonate under the influence of Cs2CO3/DMSO (100-110 °C, 5 h) in 61% and 63%, respectively. Compound 3j was purchased from commercial source
38. The compound 11 must be formed via a double Barbier type allylation as in our previous Letter,4a however, the reactivity of 3k was sluggish than other examples in this Letter. Interestingly, we observed the formation of allyl ester 12 in low yield (19%) together. For the similar In-catalyzed transesterification, see: Ranu, B. C.; Dutta, P.; Sarkar, A. J. Org. Chem. 1998, 63, 6027-6028.