3-Fluoropiperidines and N-methyl-3-fluoropiperidinium salts: The persistence of axial fluorine

Chemistry - A European Journal

Volumn 11, Issue 5, 2005, Pages 1579-1591

  Sun, Aiming ^a   Lankin, David C ^b,c   Hardcastle, Kenneth ^a   Snyder, James P ^a  

^a EMORY UNIVERSITY   (United States)

^b PFIZER INC   (United States)

^c UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

Author keywords

3 Fluoropiperidines; Charge dipole interactions; Conformational analysis; Density functional calculations; Fluorine; Molecular modeling

Indexed keywords

CRYSTAL STRUCTURE; HYDROGEN BONDS; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; SALTS; SYNTHESIS (CHEMICAL); WATER; X RAY ANALYSIS;

AXIAL ORIENTATIONS; FLUOROPIPERIDINE; PROTONATION; SIX-MEMBERED RING CHAIRS;

FLUORINE COMPOUNDS;

3 FLUOROPIPERIDINE DERIVATIVE; 4 DIPHENYLPIPERIDINIUM DERIVATIVE; FLUORINE; PIPERIDINE DERIVATIVE; UNCLASSIFIED DRUG; WATER;

AB INITIO CALCULATION; ARTICLE; CONFORMATIONAL TRANSITION; CRYSTAL STRUCTURE; DENSITY FUNCTIONAL THEORY; DIPOLE; FLUORINATION; HYDROGEN BOND; MOLECULAR MODEL; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PROTON TRANSPORT; SOLVATION; STEREOCHEMISTRY; SYNTHESIS; X RAY CRYSTALLOGRAPHY;

EID: 84962377223     PISSN: 09476539     EISSN: None     Source Type: Journal    
DOI: 10.1002/chem.200400835     Document Type: Article

References (73)

1. E. L. Eliel, S. H. Wilen, Stereochemistry of Organic Compounds, Wiley, New York, 1994.
2. F.-A. Kang, C.-L. Yin, J. Am. Chem. Soc. 1997, 119, 8562-8563.
3. a) F. A. L. Anet, J. Krane, W. Kitching, D. Doddrell, D. Praeger, Tetrahedron Lett. 1974, 15, 3255-3258;
4. b) P. F. Barron, D. Doddrell, W. J. Kitching, J. Organomet. Chem. 1977, 6, 361-383;
5. c) K. Kwetkat, W. J. Kitching, J. Chem. Soc. Chem. Commun. 1994, 345-347.
6. a) B. Cornett, M. Davis, S. Wu, N. Nevins, J. P. Snyder, J. Am. Chem. Soc. 1998, 120, 12145-12146;
7. b) M. C. Davis, B. Cornett, S. Wu, J. P. Snyder, J. Am. Chem. Soc. 1999, 121, 11864-11870.
8. E. L. Eliel, S. H. Wilen, Stereochemistry of Organic Compounds, Wiley, New York, 1994, pp. 686-726, 740-754.
9. Conformational Behavior of Six-Membered Rings, (Ed.: E. Juaristi), VCH Publishers, 1995.
10. D. C. Lankin, N. S. Chandrakumar, S. N. Rao, D. P. Spangler, J. P. Snyder, J. Am. Chem. Soc. 1993, 115, 3356-3357.
11. J. P. Snyder, N. S. Chandrakumar, H. Sato, D. C. Lankin, J. Am. Chem. Soc. 2000, 122, 544-545.
12. D. C. Lankin, G. L. Grunewald, F. A. Romero, I. Y. Oren, J. P. Snyder, Org. Lett. 2002, 4, 3557-3560.
13. a) C. H. Bushweller in Conformational Behavior of Six-Membered Rings, (Ed.: E. Juaristi), VCH Publishers, 1995, Ch 2, p. 25;
14. b) E. L. Eliel, S. H. Wilen, Stereochemistry of Organic Compounds, Wiley, New York, 1994, p. 696.
15. + leads to the following Mulliken charge distribution: N -0.32, C -0.20, H +0.18. Within the NBO framework,[12,25] the charges for the same structure are: Becke3LYP, N -0.31, C -0.35, H +0.23; MP2, N -0.29, C -0.32, H +0.21.
16. E. D. Glendening, A. E. Reed, J. E. Carpenter, F. Weinhold, NBO Version 3.1 as implemented in Gaussian 98; [45] A. E. Reed, L. A. Curtiss, F. Weinhold, Chem. Rev. 1988, 88, 899-926; cf. http:// www.chem.wisc.edu/-nbo5/
17. E. D. Glendening, A. E. Reed, J. E. Carpenter, F. Weinhold, NBO Version 3.1 as implemented in Gaussian 98; [45] A. E. Reed, L. A. Curtiss, F. Weinhold, Chem. Rev. 1988, 88, 899-926; cf. http:// www.chem.wisc.edu/-nbo5/
18. D. S. Balley, J. A. Walder, J. B. Lambert, J. Am. Chem. Soc. 1972, 94, 177-180.
19. A. Bondi, J. Phys. Chem. 1964, 68, 441-451.
20. The C-C bond lengths in cyclohexane by electron diffraction are 1.536 Å,[16] while a combined ED and microwave study for piperidine found the C-N bond separations to be 1.472 Å.[17]
21. O. Bastiansen, L. Fernholt, H. M. Seip, H. Kambara, K. Kuchitsu, J. Mol. Struct. 1973, 18, 163-168, and references therein.
22. G. Gunderson, D. W. H. Rankin, Acta Chem. Scand. Ser. A 1983, 37, 865-874.
23. a) S. Miertus, E. Scrocco, J. Tomasi, Chem. Phys. 1981, 55, 117-129;
24. b) M. Cossi, V. Barone, R. Cammi, J. Tomasi, Chem. Phys. Lett. 1996, 255, 327-335;
25. c) M. T. Cances, V. Mennucci, J. Tomasi, J. Chem. Phys. 1997, 107, 3032-3041;
26. d) V. Barone, M. Cossi, J. Tomasi, J. Chem. Phys. 1997, 107, 3210-3221;
27. e) V. Barone, M. Cossi, J. Tomasi, J. Comput. Chem. 1998, 19, 404-417; as implemented in Gaussian 98.[46]
28. a) T. A. Halgren, J. Comput. Chem. 1996, 17, 490-519;
29. b) T. A. Halgren, J. Comput. Chem. 1996, 17, 616-641;
30. c) T. A. Halgren, R. B. Nachbar, J. Comput. Chem. 1996, 17, 587-615;
31. d) T. A. Halgren, J. Comput. Chem. 1999, 20, 730-748.
32. M. B. van Niel, I. Collins, M. S. Beer, H. B. Broughton, S. K. F. Cheng, S. C. Goodacre, A. Heald, K. L. Locker, A. M. MacLeod, D. Morrison, C. R. Moyes, D. O'Connor, A. Pike, M. Rowley, M. G. N. Russell, B. Sohal, J. A. Stanton, S. Thomas, H. Verrier, A. P. Watt, J. L. Castro, J. Med. Chem. 1999, 42, 2087-2104.
33. D. A. Klumpp, M. Garza, A. Jones, S. Mendoza, J. Org. Chem. 1999, 64, 6702-6705.
34. J. B. Lambert, H. F. Shurvell, D. A. Lightner, R. G. Cooks, Organic Structural Spectroscopy, Prentice Hall, New Jersey, 1998, pp. 47-48.
35. a) H. L. Holland, Tetrahedron Lett. 1978, 19, 881-882;
36. b) J. T. Nelson, L. J. Kurz, Magn. Reson. Chem. 1993, 31, 203-213.
37. J.-P. Berthelot, J.-C. Jacquesy, J. Levisalles, Bull. Soc. Chim. Fr. 1971, 1896-1902.
38. C. Thibaudeau, J. Plavec, J. Chattopadhyaya, J. Org. Chem. 1998, 63, 4967-4984.
39. S. M. Bachrach in Reviews in Computational Chemistry, Vol. 5 (Eds.: K. B. Lipkowitz, D. B. Boyd), Wiley-VCH, New York, 1994, pp. 171-268.
40. The charges that correspond to the electrostatic potential surfaces (ESP) of Figure 5 and S5 are somewhat different from Natural/NBO and Mulliken charges. Specifically, negative charge on nitrogen is redistributed to hydrogen atoms on C-H bonds, leading to a positive charge at nitrogen for 2a and 26. Thus, the figures illustrate a positive charge distribution ("blue") in the vicinity nitrogen. Nonetheless, the ESP charges at F and the spatially closest methyl groups are very similar to the NBO and Mulliken charges: 2a (C)H-F, + 0.22 (H) and -0.32 (F); 26 (C)H-F, +0.09, +0.16 (H) and -0.31, -0.32 (F). Consequently, in the two figures, the green-red interface corresponds to the (N)H-F(C) interactions.
41. a) R. D. Stolow, T. W. Giants, J. D. Roberts, Tetrahedron Lett. 1968, 9, 5777-5780;
42. b) R. D. Stolow, T. Groom, P. D. McMaster, Tetrahedron Lett. 1968, 9, 5781-5784.
43. Y. Terui, K. Tori, J. Chem. Soc. Perkin Trans. 2 1973, 127-133.
44. R. J. Abraham, C. J. Medforth, P. E. Smith, J. Comput.-Aided Molec. Des. 1991, 5, 205-212.
45. a) E. L. Eliel, H. D. Banks, J. Am. Chem. Soc. 1972, 94, 171-176;
46. b) E. L. Eliel, H. D. Banks, J. Am. Chem. Soc. 1972, 94, 8587-8589;
47. c) E. L. Eliel, F. Alcudia, J. Am. Chem. Soc. 1974, 96, 1939-1941.
48. a) Biomedical Aspects of Fluorine Chemistry, (Eds.: R. Filler, Y. Kobayasi), Elsevier, New York, 1982;
49. b) Biomedical Frontiers of Fluorine Chemistry, (Eds.: I. Ojima, J. R. McCarthy, J. T. Welch), ACS Symposium Series No. 639, Washington D. C., 1996;
50. c) D. O'Hagan, H. S. Rzepa, Chem. Commun. 1997, 645-652;
51. d) B. K. Park, N. R. Kitteringham, P. M. O'Neill, Annu. Rev. Pharmacol. Toxicol. 2001, 41, 443-470.
52. 2-Adrenoreceptor ligands: a) G. L. Grunewald, V. H. Dahanukar, R. K. Jalluri, K. R. Criscione, J. Med. Chem. 1999, 42, 1982-1990;
53. b) G. L. Grunewald, T. M. Caldwell, Q. Li, K. R. Criscione, J. Med. Chem. 1999, 42, 3588-3601;
54. c) G. L. Grunewald, T. M. Caldwell, Q. Li, K. R. Criscione, J. Med. Chem. 2001, 44, 2849-2856;
55. d) G. L. Grunewald, F. A. Romero, K. R. Criscione, J. Med. Chem. 2004, ASAP, DOI: 10.1021/jm049594x.
56. Serotonin-subtype receptor ligands: a) See reference [20];
57. b) D. J. Hallett, U. Gerhard, S. C. Goodacre, L. Hitzel, T. J. Sparey, S. Thomas, M. Rowley, J. Org. Chem. 2000, 65, 4984-4993;
58. c) M. Rowley, D. J. Hallett, S. Goodacre, C. Moyes, J. Crawforth, T. J. Sparey, S. Patel, R. Marwood, S. Patel, S. Thomas, L. Hitzel, D. O'Connor, N. Szeto, J. L. Castro, P. H. Hutson, A. M. MacLeod, J. Med. Chem. 2001, 44, 1603-1614.
59. a) H. S. Duewel, E. Daub, V. Robinson, J. F. Honek, Biochemistry 2001, 40, 13167-13176;
60. b) J. Feeney, J. E. McCormick, C. J. Dauer, B. Birdsall, C. M. Moody, B. A. Starkmann, D. W. Young, P. Francis, R. H. Havlin, W. D. Arnold, E. Oldfield, J. Am. Chem. Soc. 1996, 118, 870-876.
61. W. Still, M. Kahn, A. Mitra, J. Org. Chem. 1978, 43, 2923-2925.
62. N. Sperber, M. Sherlock, D. Papa, J. Am. Chem. Soc. 1953, 75, 1122-1124.
63. a) T. Parella, Magn. Reson. Chem. 1998, 36, 467-495;
64. b) W. F. Reynolds, R. G. Enriquez, J. Nat. Prod. 2002, 65, 221-244.
65. SMART Version 5.55, 2000, Bruker AXS, Inc., Analytical X-ray Systems, 5465 East Cheryl Parkway, Madison WI 53711-5373.
66. SAINT Version 6.02, 1999, Bruker AXS, Inc., Analytical X-ray Systems, 5465 East Cheryl Parkway, Madison WI 53711-5373.
67. SADABS, 1996, George Sheldrick, University of Göttingen.
68. SHELXTL V5.10, 1997, Bruker AXS, Inc., Analytical X-ray Systems, 5465 East Cheryl Parkway, Madison WI 53711-5373.
69. International Tables for X-ray Crystallography, Volume C. (Ed.: A. J. C. Wilson), Kynoch, Academic Publishers, Dordrecht, 1992, Tables 6.1.1.4 (pp. 500-502) and 4.2.6.8 (pp. 219-222).
70. F. Mohamadi, N. G. J. Richards, W. C. Guida, R. Liscamp, M. Lipton, C. Caufield, G. Chang, T. J. Hendrickson, W. C. Still, J. Comput. Chem. 1991, 12, 1110-1117; cf. http://www.schrodinger.com/Products/macromodel.html
71. M. J. Frisch, et al.; Gaussian 98 (Revision A.1), Gaussian, Inc, Pittsburgh PA, 1998; cf. http://www.gaussian.com/
72. Spartan '02, Wavefunction, Inc.; Irvine, CA; cf. http://www.wavefun.com
73. Mercury software; CSD version 5.24 (November 2002); cf. http:// www.ccdc.cam.ac.uk