Enantiospecific and regioselective opening of 2-alkyl nosylaziridines by indoles mediated by boron trifluoride. Application to a practical synthesis of a GnRH antagonist

Tetrahedron Asymmetry

Volumn 14, Issue 22, 2003, Pages 3503-3515

  Farr, Roger N ^a   Alabaster, Ramon J ^a   Chung, John Y L ^a   Craig, Bridgette ^a   Edwards, John S ^a   Gibson, Andrew W ^a   Ho, Guo Jie ^a,b   Humphrey, Guy R ^a   Johnson, Simon A ^a   Grabowski, E J J ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

^b MILLENNIUM PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 [(2,4 DINITROPHENYL)SULFONYL] 2 METHYLAZIRIDINE; 2 ISOPROPYL 1 [(4 NITROPHENYL)SULFONYL]AZIRIDINE; 2 [5 [2 (2 AZABICYCLO[2.2.2]OCT 2 YL) 1,1 DIMETHYL 2 OXOETHYL] 2 (3,5 DIMETHYLPHENYL) 1H INDOL 3 YL] N (2 PYRIDIN 4 YLETHYL)PROPAN 1 AMINE; 4 NITRO N [2 (2 PHENYL 1H INDOL 3 YL)ETHYL]BENZENESULFONAMIDE; 4 NITRO N [2 (2 PHENYL 1H INDOL 3 YL)PROPYL]BENZENESULFONAMIDE; 4 NITRO N [3 PHENYL 2 (2 PHENYL 1H INDOL 3 YL)PROPYL]BENZENE SULFONAMIDE; 4 NITRO N [PHENYL 2 (2 PHENYL 1H INDOL 3 YL)ETHYL]BENZENESULFONAMIDE; AZIRIDINE DERIVATIVE; BORON TRIFLUORIDE; GONADORELIN ANTAGONIST; INDOLE DERIVATIVE; TRYPTAMINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL REACTION KINETICS; DRUG SYNTHESIS; ENANTIOSELECTIVITY; PRIORITY JOURNAL; SUBSTITUTION REACTION;

EID: 0242710838     PISSN: 09574166     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetasy.2003.08.038     Document Type: Article

References (44)

1. Kutscher B., Bernd M., Beckers T., Polymeropoulos E.E., Engel J. Angew. Chem., Int. Ed. Engl. 36:1997;2149. and references cited therein.
2. Behre, H. M.; Nordhoff, V.; Nieschlag, E. In Ovul. Induct. Update '98; Proc. World Conf., 2nd Meeting Date 1997, Filicori, M.; Flamigni, C.; Eds. Parthenon Publishing, Carnforth, UK, 1998, p. 107.
3. Chu L., Hutchins J.E., Weber A.E., Lo J.-L., Yang Y.T., Cheng K., Smith R.G., Fisher M.H., Wyvratt M.J., Goulet M.T. Bioorg. Med. Chem. Lett. 11:2001;509-513.
4. Ashton W.T., Sisco R.M., Kieczykowski G.R., Yang Y.T., Yudkovitz J.B., Cui J., Mount G.R., Ren R.N., Wu T.-J., Shen X., Lyons K.A., Mao A.-H., Carlin J.R., Karanam B.V., Vincent S.H., Cheng K., Goulet M.T. Bioorg. Med. Chem. Lett. 11:2001;2597-2602.
5. Chu L., Lo J.-L., Yang Y.T., Cheng K., Smith R.G., Fisher M.H., Wyvratt M.J., Goulet M.T. Bioorg. Med. Chem. Lett. 11:2001;515-517.
6. Lin P., Marino D., Goulet M.T., Fisher M.H., Wyvratt M.J., Cheng K., Yang Y.-T., Lo J.-L., Smith R.G. Bioorg. Med. Chem. Lett. 11:2001;1070-1076. and references cited therein.
7. Walsh T.F., Toupence R.B., Ujjainwalla F., Young J.R., Goulet M.T. Tetrahedron. 57:2001;5233-5241.
8. Simeone J.P., Bugianesi R.L., Ponpipom M.M., Goulet M.T., Levorse M.S., Desai R.C. Tetrahedron Lett. 42:2001;6459-6461.
9. Ujjainwalla F., Walsh T.F. Tetrahedron Lett. 42:2001;6441-6445. and references cited therein.
10. Chu L., Fisher M.H., Goulet M.T., Wyvratt M.J. Tetrahedron Lett. 38:1997;3871-3874.
11. Sweeney J.B. Chem. Soc. Rev. 31:2002;247-258.
12. McCoull W., Davis F.A. Synthesis. 10:2000;1347-1365.
13. For examples of Lewis acid activation of aziridine-2-carboxylates see: (a) Sato, K.; Kozikowski, a. P. Tetrahedron Lett. 1989, 30, 4073-4076; (b) Shima, I.; Shimazaki, N.; Imai, K.; Hemmi, K.; Hashimoto, M. Chem. Pharm. Bull. 1990, 38, 564-566.
14. For examples of Lewis acid activation of aziridine-2-carboxylates see: (a) Sato, K.; Kozikowski, a. P. Tetrahedron Lett. 1989, 30, 4073-4076; (b) Shima, I.; Shimazaki, N.; Imai, K.; Hemmi, K.; Hashimoto, M. Chem. Pharm. Bull. 1990, 38, 564-566.
15. 3 catalyzed aryl addition to tosyl aziridines has appeared. See: Yadav J.S., Reddy V.S., Rao R.S., Veerendhar G., Nagaiah K. Tetrahedron Lett. 42:2001;8067-8070.
16. Farras J., Ginesta X., Sutton P.W., Taltavull J., Egeler F., Romea P., Urpi F., Vilarrasa J. Tetrahedron. 57:2001;7665-7674.
17. Assay yield was determined by reversed phase HPLC. In each case, the samples were purified by column chromatography on silica gel to obtain the desired material which was then recrystallized to obtain a working standard. Assay yield refers to the comparison of the peak area of a diluted, weighed sample of the crude reaction mixture versus a known concentration of the corresponding standard.
18. 1H NMR, reversed phase HPLC, chiral SFC.
19. Lehmann A., Grivsky B. Bull. Soc. Chim. Belg. 52:1946;75.
20. Racemic 2c: (a) Naegeli, I.; Baud, C.; Bernardinelli, G.; Jacquier, Y.; Moran, M.; Mueller, P. Helv. Chim. Acta; En. 1997, 1087-1105; Chiral (S) 2c: (b) Sutton, P. W.; Bradley, A.; Farra, J.; Romea, P.; Urpi, F.; Vilarrasa, J. Tetrahedron 2000, 56, 7947-7958.
21. Racemic 2c: (a) Naegeli, I.; Baud, C.; Bernardinelli, G.; Jacquier, Y.; Moran, M.; Mueller, P. Helv. Chim. Acta; En. 1997, 1087-1105; Chiral (S) 2c: (b) Sutton, P. W.; Bradley, A.; Farra, J.; Romea, P.; Urpi, F.; Vilarrasa, J. Tetrahedron 2000, 56, 7947-7958.
22. Cernerud M., Adolfsson H., Moberg C. Tetrahedron: Asymmetry. 8:1997;2655-2662.
23. 1H NMR and the desired product was detected however numerous other products were present as well. HPLC analysis concurred with this finding and the isolation of the product was abandoned.
24. Maligres P.E., See M.M., Askin D., Reider P.J. Tetrahedron Lett. 38:1997;5253-5256. and references cited therein.
25. Kelly J.W., Eskew N.L., Evans S.A. Jr. J. Org. Chem. 51:1986;95-97.
26. 2-Nitro, 4-nitro, and 2,4-dinitro nosyl derivatives were all prepared. The 4-nitro and 2,4-dinitro derivatives were pursued because they were crystalline solids.
27. Two reports detailing similar synthesis of nosyl aziridines were reported. See: Kim, B. M.; So, S. M.; Choi, H. J. Org. Lett. 2002, 4, 949-952; and Ref. 12.
28. Two reports detailing similar synthesis of nosyl aziridines were reported. See: Kim, B. M.; So, S. M.; Choi, H. J. Org. Lett. 2002, 4, 949-952; and Ref. 12.
29. Chen C.-Y., Lieberman D.R., Larsen R.D., Reamer R.A., Verhoeven T.R., Reider P.J. Tetrahedron Lett. 35:1994;6981-6984.
30. Tinnemans A.H.A., Laarhoven W.H. J. Chem. Soc., Perkin Trans. 2. 1976;1104-1111.
31. Melissaris A.P., Litt M.H. J. Org. Chem. 57:1992;6998-6999.
32. MEBYNOL is available in bulk and even the cost from Aldrich is @ $40 per liter.
33. This procedure is a modification of the Litt procedure, Ref. 27.
34. Castro C.E., Gaughan E.J., Owsley D.C. J. Org. Chem. 31:1966;4071-4078. and references cited therein.
35. Fukuyama T., Jow C.-K., Cheung M. Tetrahedron Lett. 36:1995;6373-6374.
36. Fukuyama T., Cheung M., Jow C.-K., Hidai Y., Kan T. Tetrahedron Lett. 38:1997;5831-5834.
37. Pyridyl ethanol 18 is converted to 4-vinyl pyridine as a side product under the reaction conditions. Therefore, an excess of reagents is required to get complete conversion to the desired product.
38. Fukuyama reported that the 2,4-dinitro analogs were more labile to basic conditions than their corresponding 4-nitro analogs. See Refs. 31 and 32.
39. Chung J.Y.L., Ho G.-J. Synth. Commun. 32:2002;1985-1995.
40. The reagent is available from Aldrich (@ $11 per liter) and does not have a significant odor.
41. Katritzky A.R., Khan G.R., Marson C.M. J. Heterocyclic Chem. 24:1987;641-644.
42. Philips A.P. J. Am. Chem. Soc. 78:1956;4441-4443.
43. RajanBabu T.V., Reddy G.S., Fukunaga T. J. Am. Chem. Soc. 107:1985;5473-5483.
44. RajanBabu T.V., Chenard T.V., Bertrand L., Petti M.A.T. J. Org. Chem. 51:1986;1704-1712.