Concise synthesis of the bicyclic scaffold of n-methylwelwitindolinone c isothiocyanate via an indolyne cyclization

Organic Letters

Volumn 11, Issue 11, 2009, Pages 2349-2351

  Tian, Xia ^a   Huters, Alexander D ^a   Douglas, Colin J ^a   Garg, Neil K ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALKALOID; INDOLE DERIVATIVE; N METHYLWELWITINDOLINONE C ISOTHIOCYANATE; N-METHYLWELWITINDOLINONE C ISOTHIOCYANATE; OXINDOLE;

ARTICLE; CHEMICAL STRUCTURE; CHEMISTRY; CONFORMATION; CYCLIZATION; OXIDATION REDUCTION REACTION; STEREOISOMERISM; SYNTHESIS; X RAY CRYSTALLOGRAPHY;

ALKALOIDS; CRYSTALLOGRAPHY, X-RAY; CYCLIZATION; INDOLES; MOLECULAR CONFORMATION; MOLECULAR STRUCTURE; OXIDATION-REDUCTION; STEREOISOMERISM;

EID: 66149173395     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol9007684     Document Type: Article

References (42)

1. Stratmann, K.; Moore, R. E.; Bonjouklian, R.; Deeter, J. B.; Patterson, G. M. L.; Shaffer, S.; Smith, C. D.; Smitka, T. A. J. Am. Chem. Soc. 1994, 116, 9935-9942.
2. 1 has sometimes been referred to as "welwistatin"; however, as originally defined in ref 3b, "welwistatin" refers to the des-N-methyl analogue of 1.
3. Smith, C. D.; Zilfou, J. T.; Stratmann, K.; Patterson, G. M.; Moore, R. E. Mol. Pharmacol. 1995, 47, 241-247.
4. Zhang, X.; Smith, C. D. Mol. Pharmacol. 1996, 49, 288-294.
5. Avendaño, C.; Mene'ndez, J. C. Curr. Med. Chem. 2002, 9, 159-193.
6. At concentrations as low as 0.1 μM, 1 was found to greatly decrease the IC50 of vinblastine, taxol, actinomycin D, cochicines, and daunomycin in MCF-7/ADR drug-resistant breast carcinoma cells.
7. For a review, see: Avendaño, C.; Mene'ndez, J. C. Curr. Org. Synth.2004, 1, 65-82.
8. Wood, J. L.; Holubec, A. A.; Stoltz, B. M.; Weiss, M. M.; Dixon, J. A.; Doan, B. D.; Shamji, M. F.; Chen, J. M.; Heffron, T. P. J. Am. Chem. Soc. 1999, 121, 6326-6327.
9. Ready, J. M.; Reisman, S. E.; Hirata, M.; Weiss, M. M.; Tamaki, K.; Ovaska, T. V.; Wood, J. L. Angew. Chem., Int. Ed. 2004, 43, 1270-1272.
10. Jung, M. E.; Slowinski, F. Tetrahedron Lett. 2001, 42, 6835-6838.
11. Deng, H.; Konopelski, J. P. Org. Lett. 2001, 3, 3001-3004.
12. Xia, J.; Brown, L. E.; Konopelski, J. P. J. Org. Chem. 2007, 72, 6885-6890.
13. MacKay, J. A.; Bishop, R. L.; Rawal, V. H. Org. Lett. 2005, 7, 3421-3424.
14. Baudoux, J.; Blake, A. J.; Simpkins, N. S. Org. Lett. 2005, 7, 4087-4089.
15. Boissel, V.; Simpkins, N. S.; Bhalay, G.; Blake, A. J.; Lewis, W. Chem. Commun. 2009, 1398-1400.
16. Greshock, T. J.; Funk, R. L. Org. Lett. 2006, 8, 2643-2645.
17. Lauchli, R.; Shea, K. J. Org. Lett. 2006, 8, 5287-5289.
18. Richter, J. M.; Ishihara, Y.; Masuda, T.; Whitefield, B. W.; Llamas, T.; Pohjakallio, A.; Baran, P. S. J. Am. Chem. Soc. 2008, 130, 17938-17954.
19. For seminal studies involving indolynes, see: Julia, M.; Huang, Y.; Igolen, J. C. R. Acad. Sci., Ser. C 1967, 265, 110-112.
20. Igolen, J.; Kolb, A. C. R. Acad. Sci., Ser. C 1969, 269, 54-56. For related studies, see:
21. Julia, M.; Le Goffic, F.; Igolen, J.; Baillarge, M. C. C. R. Acad. Sci., Ser. C 1967, 264, 118-120.
22. Julia, M.; Igolen, J.; Kolb, A. C. R. Acad. Sci., Ser. C 1971, 273, 1776-1777.
23. In a previous study, we demonstrated that indolynes function as practical electrophilic indole surrogates and can also be accessed from indolylsilyltriflate species under mild fluoride-mediated conditions, see: Bronner, S. M.; Bahnck, K. B.; Garg, N. K. Org. Lett. 2009, 11, 1007-1010.
24. For the preparation of indolynes from dihaloindoles and butyllithium reagents, and subsequent Diels-Alder studies, see: Buszek, K. R.; Luo, D.; Kondrashov, M.; Brown, N.; VanderVelde, D. Org. Lett. 2007, 9, 4135-4137.
25. Brown, N.; Luo, D.; VanderVelde, D.; Yang, S.; Brassfield, A.; Buszek, K. R. Tetrahedron Lett. 2009, 50, 63-65.
26. Buszek, K. R.; Brown, N.; Luo, D. Org. Lett. 2009, 11, 201-204.
27. For reviews regarding the chemistry of arynes, see: Pellissier, H.; Santelli, M. Tetrahedron 2003, 59, 701-730.
28. Wenk, H. H.; Winkler, M.; Sander, W. Angew. Chem., Int. Ed. 2003, 42, 502-528.
29. Sanz, R. Org. Prep. Proced. Int. 2008, 40, 217-291.
30. 7 is commercially available or can be easily prepared in one step from inexpensive 5-bromoindole on a multigram scale, see: Jiang, X.; Tiwari, A.; Thompson, M.; Chen, Z.; Cleary, T. P.; Lee, T. B. K. Org. Proc. Res. Dev. 2001, 5, 604-608.
31. Thulasiram, H. V.; Gadad, A. K.; Madyastha, M. K. Drug Metab. Dispos. 2000, 28, 833-844.
32. Wang, S.-Y.; Ji, S.-J.; Loh, T.-P. Synlett 2003, 15, 2377-2379.
33. The reaction of 4-bromo-N-methylindole with enone 8 was unsuccessful under a variety of reaction conditions, likely because of steric hinderance imposed by the C4 substituent.
34. Aggarwal, V. K.; Daly, A. M. Chem. Commun. 2002, 2490-2491.
35. Caubere, P. Acc. Chem. Res. 1974, 7, 301-308.
36. Alternative basic conditions commonly used to promote aryne formation were unsuccessful (e.g., LDA, LHMDS, Me2Zn(TMP)Li).
37. Prolonged reaction times led to olefin isomerization of enol ether 13 to afford the corresponding tetrasubstituted olefin.
38. Utilization of the TBS or TIPS enol ether derivatives of 5 did not lead to improvements in yield or selectivity for C-arylation.
39. Variations in temperature, stoichiometry, and counterion did not lead to improvements in the conversion of 5 to 3.
40. Shen, K.; Fu, Y.; Li, J.-N.; Liu, L.; Guo, Q.-X. Tetrahedron 2007, 63, 1568-1576.
41. omoindole is commercially available from Combi-Blocks, Inc. at a cost of $24 per 25 grams; the cost of 4-bromoindole is $195 per 25 grams.
42. Greshock, T. J. Ph.D. Dissertation. Pennsylvania State University, University Park, PA, 2006.