Enantioselective synthesis of nicotinic receptor probe 7,8-difluoro-1,2,3, 4,5,6-hexahydro-1,5-methano-3-benzazocine

Organic Letters

Volumn 8, Issue 26, 2006, Pages 5947-5950

  Bashore, Crystal G ^a   Vetelino, Michael G ^a   Wirtz, Michael C ^a   Brooks, Paige R ^a   Frost, Heather N ^a   McDermott, Ruth E ^a   Whritenour, David C ^a   Ragan, John A ^a   Rutherford, Jennifer L ^a   Makowski, Teresa W ^a   Brenek, Steven J ^a   Coe, Jotham W ^a  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

7,8 DIFLUORO 1,2,3,4,5,6 HEXAHYDRO 1,5 METHANO 3 BENZAZOCINE; 7,8-DIFLUORO-1,2,3,4,5,6- HEXAHYDRO-1,5-METHANO-3-BENZAZOCINE; DRUG DERIVATIVE; NICOTINE; NICOTINIC RECEPTOR; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL STRUCTURE; CHEMISTRY; MOLECULAR PROBE; STEREOISOMERISM; SYNTHESIS; X RAY CRYSTALLOGRAPHY;

CRYSTALLOGRAPHY, X-RAY; MODELS, MOLECULAR; MOLECULAR PROBES; NICOTINE; RECEPTORS, NICOTINIC; STEREOISOMERISM;

EID: 33846179321     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol0623062     Document Type: Article

References (20)

1. For leading reviews in this area, see: (a) Bunnelle, W. H.; Dart, M. J.; Schrimpf, M. R. Curr. Med. Chem. 2004, 4, 299-334.
2. (b) Holladay, M. W.; Dart, M. J.; Lynch, J. K. J. Med. Chem. 1997, 40, 4169-4194.
3. (c) Glennon, R. A.; Dukat, M. Med. Chem. Res. 1996, 465-486.
4. Coe, J. W.; Vetelino, M. G.; Bashore, C. G.; Wirtz, M. C.; Brooks, P. R.; Arnold, E. P.; Lebel, L. A.; Fox, C. B.; Sands, S. B.; Davis, T. I.; Rollema, H.; Schaeffer, E.; Schulz, D. W.; Tingley, F. D., III; O'Neill, B. T. Bioorg. Med. Chem. Lett. 2005, 15, 2974-2979.
5. Coe, J. W. Arylfused Azapolycyclic Compounds. PCT Int. Appl. WO99 55,680, 1999. U.S. Patent 6,462,035, October 8, 2002, and U.S. Patent 6,706,702, March 16, 2004.
6. The ortho-lithio anisole intermediate failed to react with Weinreb amides at low temperature and, upon warming, presumably suffered from benzyne-mediated decomposition before any addition to the amide.
7. Brooks, P. R.; Wirtz, M. C.; Vetelino, M. G.; Rescek, D. M.; Woodworth, G. F.; Morgan, B. P.; Coe, J. W. J. Org. Chem. 1999, 64, 9719-9721.
8. Lithiated 3,4-difluorobromobenzene failed to react with the corresponding Weinreb amide.
9. In theory, with optically enriched alcohol, chiral induction in the Heck cyclization step should be possible.
10. Hayan, S. E.; Domagala, J. M.; Heifetz, C. L.; Johnson, J. J. Med. Chem. 1991, 34, 1155-1161.
11. Bashore, C. G.; Samardjiev, I. J.; Bordner, J.; Coe, J. W. J. Am. Chem. Soc. 2003, 125, 3268-3272.
12. Vedejs, E.; Engler, D. A.; Mullins, M. J. J. Org. Chem. 1977, 42, 3102-3113.
13. (a) Deprés, J.-P.; Greene, A. E. J. Org. Chem. 1984, 49, 928-931.
14. (b) Deprés, J.-P.; Greene, A. E. Org. Synth. 1997, 75, 195-200.
15. (c) Johnson, C. R.; Keiser, J. E.; Sharp, J. C. J. Org. Chem. 1969, 34, 860-864.
16. (a) Su, T. M.; Sliwinski, W. F.; Schleyer, P. v. R. J. Am. Chem. Soc. 1969, 91, 5386-5388.
17. (b) Stang, P. J.; Hanack, M.; Subramanian, L. R. Synthesis 1982, 85-126.
18. (c) Bashore, C. G.; Samardjiev, I. J.; Bordner, J.; Coe, J. W. J. Am. Chem. Soc. 2003, 125, 3268-3272.
19. Gas-phase calculations of carbopallidation adducts before β-hydride elimination were performed, but the results did not align with the observed sense of enantiofacial induction.
20. Ogino, T.; Mochzuki, K. Chem. Lett. 1979, 443-446.