Stereoselective formation of carbon-carbon bonds via SN2- displacement: Synthesis of substituted cycloalkyl[b]indoles

Journal of Organic Chemistry

Volumn 70, Issue 21, 2005, Pages 8385-8394

  Hillier, Michael C ^a   Marcoux, Jean François ^a   Zhao, Dalian ^a   Grabowski, Edward J J ^a   McKeown, Arlene E ^a   Tillyer, Richard D ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALCOHOLS; ALKYLATION; CONDENSATION; KETONES; SYNTHESIS (CHEMICAL);

CARBON STEREOCENTERS; CARBON-CARBON BONDS; CYCLIZATION; STEREOSELECTIVE FORMATION;

CARBON;

ALCOHOL DERIVATIVE; ALKYL GROUP; BIS(2,2,2 TRICHLOROETHYL)AZODICARBOXYLATE; BORANE DERIVATIVE; CARBON; DICARBOXYLIC ACID; HETEROCYCLIC KETONE; INDOLE DERIVATIVE; PHOSPHINE DERIVATIVE; TRIMETHYLPHOSPHINE; UNCLASSIFIED DRUG;

ALKYLATION; ARTICLE; CHEMICAL BOND; CYCLIZATION; DESICCATION; ENANTIOMER; FISCHER CYCLIZATION; JAPP KLINGEMANN CONDENSATION; MITSUNOBU REACTION; POLYMERIZATION; REDUCTION; STEREOCHEMISTRY; SUBSTITUTION REACTION; SYNTHESIS;

CARBON; CYCLIZATION; INDOLES; MOLECULAR STRUCTURE; STEREOISOMERISM;

EID: 26844479020     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo051146p     Document Type: Article

References (51)

1. (a) Asselin, A. A.; Humber, L. G.; Komlossy, J. J. Med. Chem. 1976, 19, 792-797.
2. (b) Asselin, A. A.; Humber, L. G.; Dobson, T. A. U.S. Patent 4,057,599, 1977.
3. (c) Failli, A. A.; Steffan, R. J.; Kreft, A. F.; Caggiano, T. J.; Caufield, C. E. U.S. Patent 5 830 911, 1998.
4. (d) Kong, Y. C.; Ng, K. H.; Wat, K. H.; Wong, A.; Saxena, I. F.; Cheng, K. F.; But, P. P. H.; Chang, H. T. Planta Med. 1985, 50, 304-307.
5. (e) Cheng, K. F.; Cheung, M, K.; Kong, Y. C. Aust. J. Chem. 1997, 50, 349-353.
6. (f) Dionne, G.; Asselin, A. A.; Humber, L. G. U.S. Patent 4,235,903, 1098.
7. Breyer, R. M.; Bagdassarian, C. K.; Myers, S. A.; Breyer, D. Annu. Rev. Pharmacol Toxicol. 2001, 41, 661-690.
8. Anonymous, Expert Opin. Ther. Patents 2002, 12, 597-599.
9. (a) McMenamin, P. Ann. Allergy 1994, 73, 35-39.
10. (b) Tang, R. B.; Tsai, L. C.; Hwang, H. M.; Hwang, B.; Wu, K. G.; Hung, M. W. Clin. Exp. Allergy 1990, 20, 33-38.
11. (a) Guindon, Y.; Yoakim, C.; Gillard, J. W.; Girard, Y. Eur. Patent 0 300 676, 1984.
12. (b) Labelle, M.; Sturino, C.; Roy, B. WO Patent 01/79169 A2, 2001.
13. (c) Labelle, M.; Sturino, C.; Roy, B.; Berthelette, C.; Boyd, M.; Lachance, N.; Scheigetz, J. WO Patent 02/008186 A2, 2002.
14. (d) Berthelette, C.; Lachance, N.; Li, L.; Sturino, C.; Zhaoyin, W. WO Patent 03/062200 A2, 2003.
15. (e) Li, L.; Beaulieu, C.; Guay, D.; Sturino, C.; Wang, Z. WO Patent 04/103970 A1, 2004.
16. (f) Lachance, N.; Sturino, C. WO Patent 04/111047 A2, 2004.
17. (g) Berthelette, C.; Boyd, M. J.; Lachance, N.; Roy, B.; Sturino, C. F.; Scheigetz, J.; Zamboni, R. J. J. Labelled Compd. Radiopharm. 2004, 47, 107-113.
18. Shafiee, A.; Upadhyay, V.; Corley, E. G.; Biba, M.; Zhao, D.; Marcoux, J.-F.; Campos, K. R.; Journet, M.; King, A. O.; Larsen, R. D.; Grabowski, E. J. J.; Volante, R. P.; Tillyer, R. D. Tetrahedron: Asymmetry, in press.
19. (a) Campos, K. R.; Journet, M.; Lee, S.; Grabowski, E. J. J.; Tillyer, R. D. J. Org. Chem. 2005, 70, 268-274.
20. (b) Evans, D. A.; Fandrick, K. R.; Song, H.-J. J. Am. Chem. Soc. 2005, 127, 8942-8943.
21. (a) Ashwell, M. A. WO Patent 94/08983, 1994.
22. (a) Uenishi, J.; Hamada, M. Chem. Pharm. Bull. 2002, 50, 687-700.
23. (b) Uenishi, J.; Hamada, M. Synthesis 2002, 625-630.
24. (c) Bolshan, Y.; Chen, C.-y.; Chilenski, J. R.; Gosselin, F.; Mathre, D. J.; O'Shea, P. D.; Roy, A.; Tillyer, R. D. Org. Lett. 2004, 6, 111-114.
25. (d) O'Shea, P. D.; Chen, C.-y.; Chen, W.; Dagneau, P.; Frey, L. F.; Grabowski, E. J. J.; Marcantonio, K. M.; Reamer, R. A.; Tan, L.; Tillyer, R. D.; Roy, A.; Wang, X.; Zhao, D. J. Org. Chem. 2005, 70, 3021-3030.
26. Hillier, M. C.; Desrosiers, J.-N.; Marcoux, J.-F.; Grabowski, E. J. J. Org. Lett. 2004, 6, 573-576.
27. (a) Lions, F. J. Proc. R. Soc. N. S. Wales 1932, 66, 516-525.
28. (b) Phillips, R. R. Organic Reactions; John Wiley and Sons: New York, 1959; Vol. 10, pp 143-178.
29. See: Linstead, R. P.; Wang, A. B.-L. J. Chem. Soc. 1937, 807-814 and references therein.
30. (a) Hartman, W. W.; Dickey, J. B. Organic Synthesis; Wiley: New York 1948; Collect Vol. II, pp 163-265.
31. (b) Štefane, B.; Kocevar, M.; Polanc, S. J. Org. Chem. 1997, 62, 7165-7169.
32. The hydrazone was isolated as an inseparable mixture of isomers.
33. The yield of the methoxy-substituted derivative 7d was lower due to some decomposition that was observed during the reaction.
34. For similar conditions, see: (a) Fink, D. M.; Palermo, M. G.; Bores, G. M.; Huger, F. P.; Kurys, B. E.; Merriman, M. C.; Olsen, G. E.; Petko, W.; O'Malley, G. J. Bioorg. Med. Chem. Lett. 1996, 6, 625-630.
35. (b) Xing, C.; Wu, P.; Skibo, E. B. J. Med. Chem. 2000, 43, 457-466.
36. (c) Skibo, E. B.; Xing, C.; Dorr, R. T. J. Med. Chem. 2001, 44, 3545-3562.
37. The mono-fluoro derivative 10d could be removed by column chromatography. (17) (a) Brook, G. M. J. Chem. Soc., Perkin Trans. 1 1983, 4, 821-825.
38. (b) Benke, F. D.; Brook, G. M. J. Fluorine Chem. 1984, 26, 77-86.
39. Protection of the indole nitrogen under non-phase-transfer conditions led to poor product yield due to decomposition.
40. (a) Mathre, D. J.; Thompson, A. S.; Douglas, A. W.; Hoogsteen, K.; Carroll, J. D.; Corley, E. G.; Grabowski, E. J. J. J. Org. Chem. 1993, 58, 2880-2888.
41. (b) Corey, E. J.; Helal, C. J. Angew. Chem., Int. Ed. Engl. 1998, 37, 1986-2012.
42. In general, we found these substrates to be very unreactive under catalytic OAB reducing conditions.
43. For example, 14a could be completely converted to racemic 15 upon standing as a solution in MeOH after 24 h.
44. For a general review, see: Blaser, H.-U.; Malan, C.; Pugin, B.; Spindler, F.; Steiner, H.; Studer, M. Adv. Synth. Catal. 2003, 345, 103-151.
45. Noyori, R.; Tomino, I.; Tanimoto, Y.; Nishizawa, M. J. Am. Chem. Soc. 1984, 106, 6709-6716.
46. Two equivalents of each reagent with respect to starting material was required for complete conversion to product for the Mitsunobu displacement reaction.
47. Diisopropylazodicarboxylate (DIAD) could be used instead of DEAD with little affect on the reaction outcome.
48. The addition of DEAD is exothermic and can result in a 20 °C temperature change during uncontrolled reagent addition.
49. This substrate (17f) is extremely sensitive and rapidly decomposes in the presence of acid.
50. Joseph, D.; Martarello, L.; Kirsch, G. J. Chem. Res. (M) 1995, 2001-2114.
51. Sangeetha, V.; Prasad, K. J. R. Heterocycl. Commun. 2002, 8, 65-70.