Structural and rate studies of the formation of substituted benzynes

Journal of the American Chemical Society

Volumn 130, Issue 11, 2008, Pages 3406-3412

  Riggs, Jason C ^a   Ramirez, Antonio ^a   Cremeens, Matthew E ^a   Bashore, Crystal G ^b   Candler, John ^b   Wirtz, Michael C ^b   Coe, Jotham W ^b   Collum, David B ^a  

^a Department of Obstetrics Gynecology   (United States)

^b PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

NONDISSOCIATIVE PATHWAYS; SUBSTITUTED BENZYNES;

ELECTRONS; MONOMERS; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; REGIOSELECTIVITY; SOLVENTS;

BENZENE;

BENZENE DERIVATIVE; BENZYNE; LITHIUM CHLORIDE; LITHIUM FLUORIDE; MONOMER; SOLVENT; UNCLASSIFIED DRUG;

ARTICLE; CARBON NUCLEAR MAGNETIC RESONANCE; CONCENTRATION RESPONSE; DENSITY FUNCTIONAL THEORY; DISSOCIATION; ELIMINATION REACTION; STRUCTURE ANALYSIS;

BENZENE DERIVATIVES; COMPUTER SIMULATION; HYDROCARBONS, HALOGENATED; KINETICS; LITHIUM; MAGNETIC RESONANCE SPECTROSCOPY; MODELS, CHEMICAL; MOLECULAR STRUCTURE; ORGANOMETALLIC COMPOUNDS; SOLVENTS;

EID: 41449083248     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja0754655     Document Type: Article

References (105)

1. (a) Ozkan, I.; Kinal, A. J. Org. Chem. 2004, 69, 5390.
2. (b) De Proft, F.; Schleyer, P. v. R.; van Lenthe, J. H.; Stahl, F.; Geerlings, P. Chem. - Eur. J. 2002, 8, 3402.
3. (c) Johnson, W. T. G.; Cramer, C. J. J. Phys. Org. Chem. 2001, 14, 597.
4. (d) Jiao, H.; Schleyer, P. v. R.; Beno, B. R.; Houk, K. N.; Warmuth, R. Angew. Chem., Int. Ed. Engl. 1997, 36, 2761.
5. (e) Radziszewski, J. G.; Hess, B. A. Jr.; Zahradnik, R. J. Am. Chem. Soc. 1992, 114, 52, and references cited therein,
6. (f) Wenthold, P. G.; Paulino, J. A.; Squires, R. R. J. Am. Chem. Soc. 1991, 113, 7414.
7. (g) Gronert, S.; DePuy, C. H. J. Am. Chem. Soc. 1989, 111, 9253.
8. (h) Hoffmann, R. W. Dehydrobenzene and Cycloalkynes; Academic Press: New York, 1967.
9. Recent reviews on benzyne: (a) Dyke, A. M.; Hester, A. J.; Lloyd-Jones, G. C. Synthesis 2006, 4093.
10. (b) Pellissier, H.; Santelli, M. Tetrahedron 2003, 59, 701.
11. (c) Wenk, H. H.; Winkler, M.; Sander, W. Angew. Chem., Int. Ed. 2003, 42, 502.
12. (d) Nájera, C.; Sansano, J. M.; Yus, M. Tetrahedron 2003, 59, 9255.
13. (e) Leroux, F.; Schlosser, M. Angew. Chem., Int. Ed. 2002, 41, 4272.
14. Recent examples of generation of benzyne from haloaryllithiums: (i) via LiF elimination: (a) Sanz, R.; Fernandez, Y.; Castroviejo, M. P.; Perez, A.; Fañanas, F. J. J. Org. Chem. 2006, 71, 6291.
15. (b) Heiss, C.; Leroux, F.; Schlosser, M. Eur. J. Org. Chem. 2005, 24, 5242.
16. (c) Kudzma, L. V. Synthesis 2003, 1661.
17. (d) Dyer, P. W.; Fawcett, J.; Hanton, M. J.; Kemmitt, R. D. W.; Padda, R.; Singh, N. J. Chem. Soc., Dalton Trans. 2003. 104.
18. (e) Pawlas, J.; Begtrup, M. Org. Lett. 2002, 4, 2687.
19. (f) Caster, K. C.; Keck, C. G.; Walls, R. D. J. Org. Chem. 2001, 66, 2932.
20. (ii) Via LiCl elimination: (g) Heiss, C.; Cottet, F.; Schlosser, M. Eur. J. Org. Chem. 2005, 24, 5236.
21. (h) Shoji, Y.; Hari, Y.; Aoyama, T. Tetrahedron Lett. 2004, 45, 1769.
22. (i) Bennet, M. A.; Kopp, M. R.; Wenger, E.; Willis, A. C. J. Organomet. Chem. 2003, 667, 8.
23. (j) Gohier, F.; Castanet, A.-S.; Mortier, J. Org. Lett. 2003, 5, 1919.
24. (k) Faigl, F.; Marzi, E.; Schlosser, M. Chem. - Eur. J. 2000, 6, 771.
25. (l) Wang, A.; Zhang, H.; Biehl, E. R. Heterocycles 2000, 52, 1133.
26. (iii) From 3-haloanisoles: (m) Biland-Thommen, A. S.; Raju, G. S.; Blagg, J.; White, A. J. P.; Barrett, A. G. M. Tetrahedron Lett. 2004, 45, 3181.
27. (n) Bauta, W. E.; Lovett, D. P.; Cantrell, Jr. W. R.; Burke, B. D. J. Org. Chem. 2003, 68, 5967.
28. (o) Becht, J.-M.; Gissot, A.; Wagner, A.; Mioskowski, C. Chem. - Eur. J. 2003, 9, 3209.
29. (p) Kita, Y.; Higuchi, K.; Yoshida, Y.; Iio, K.; Kitagaki, S.; Ueda, K.; Akai, S.; Fujioka, H. J. Am. Chem. Soc. 2001, 123, 3214.
30. Rollema, H.; Coe, J. W.; Chambers, L. K.; Hurst, R. S.; Stahl, S. M.; Williams, K. E. Trends Pharmacol. Sci. 2007, 28, 316.
31. (a) Coe, J. W.; Brooks, P. R. P. U.S. Cont.-in-part of Appl. No. PCT/IB98/01813, US 6605610, 2003.
32. (b) Coe, J. W.; et al. J. Med. Chem. 2005, 48, 3474.
33. (i) Synthesis via formation of 3-halobenzyne: (a) Coe, J. W.; Wirtz, M. C.; Bashore, C. G.; Candler, J. Org. Lett. 2004, 6, 1589.
34. (ii) For alternative routes, see: (b) Brooks, P. R.; Caron, S.; Coe, J. W.; Ng, K. K.; Singer, R. A.; Vazquez, E.; Vetelino, M. G.; Watson, Jr. H. H.; Whritenour, D. C.; Wirtz, M. C. Synthesis 2004, 1755.
35. (c) Singer, R. A.; McKinley, J. D.; Barbe, G.; Farlow, R. A. Org. Lett. 2004, 6, 2357.
36. Ramirez, A.; Candler, J.; Bashore, C. G.; Wirtz, M. C.; Coe, J. W.; Collum, D. B. J. Am. Chem. Soc. 2004, 126, 14700.
37. (a) Hoffmann, D.; Collum, D. B. J. Am. Chem. Soc. 1998, 120, 5810.
38. (b) Kottke, T.; Stalke, D. Angew. Chem., Int. Ed. Engl. 1993, 32, 580.
39. 19F has I = 1/2.
40. F-C values have been observed for related 2-fluorophenyl-lithiums: (a) Singh, K. J.; Collum, D. B. J. Am. Chem. Soc. 2006, 128, 13753.
41. (b) Menzel, K.; Fisher, E. L.; DiMichele, L.; Frantz, D. E.; Nelson, T. D.; Kress, M. H. J. Org. Chem. 2006, 71, 2188.
42. 13C atom: (c) Doddrell, D.; Jordan, D.; Riggs, N. V. J. Chem. Soc., Chem. Commun. 1972, 1158.
43. (d) Doddrell, D.; Barfield, M.; Adcock, W.; Aurangzeb, M.; Jordan, D. J. Chem. Soc., Perkin Trans. 2 1976, 402.
44. (a) X-ray of monomelic 2,3,4,5-tetrafluorophenyllithium: Kottke, T.; Sung, K.; Lagow, R. J. Angew. Chem., Int. Ed. Engl. 1995, 34, 1517.
45. (b) For a related monomer, see: Bosold, F.; Zulauf, P.; Marsch, M.; Harms, K.; Lohrenz, J.; Boche, G. Angew. Chem., Int. Ed. Engl. 1991, 30, 1455.
46. (c) 2,3,5,6-Tetrafluorophenyllithium exists as a monomer in THF: Stratakis, M.; Wang, P. G.; Streitwieser, A. J. Org. Chem. 1996, 61, 3145.
47. (a) Schlosser, M. In Organometallics in Synthesis: A Manual, 2nd ed.; Schlosser, M., Ed.; John Wiley & Sons: Chichester, 2002; Chapter 1.
48. (b) Reich, H. J.; Green, D. P.; Medina, M. A.; Goldenberg, W. S.; Gudmundsson, B. Ö.; Dykstra, R. R.; Phillips, N. H. J. Am. Chem. Soc. 1998, 120, 7201.
49. (c) Seebach, D. Angew. Chem., Int. Ed. Engl. 1988, 22, 1624.
50. (a) Reich, H. J.; Goldenberg, W. S.; Sanders, A. W.; Jantzi, K. L.; Tzschucke, C. C. J. Am. Chem. Soc. 2003, 125, 3509.
51. (b) Reich, H. J.; Goldenberg, W. S.; Gudmundsson, B. Ö.; Sanders, A. W.; Kulicke, K. J.; Simon, K.; Guzei, I. A. J. Am. Chem. Soc. 2001, 123, 8067.
52. (c) Reich, H. J.; Sikorski, W. H.; Gudmundsson, B. Ö.; Dykstra, R. R. J. Am. Chem. Soc. 1998, 120, 4035.
53. Rates of benzyne formation from aryllithiums 9 and 10 showed inverse dependencies at low arene concentrations due to incomplete metalation at low temperatures.
54. The initial rates (Δ[arene]/Δt) were converted to their corresponding observed first-order rate constants Otobsd, see Supporting Information).
55. (a) Remenar, J. F.; Collum, D. B. J. Am. Chem. Soc. 1998, 120, 4081.
56. (b) Remenar, J. F.; Collum, D. B. J. Am. Chem. Soc. 1997, 119, 5573.
57. Hart, H.; Lai, C.; Chukuemeka, G.; Shamouilian, S. Tetrahedron 1987, 43, 5203.
58. Espenson, J. H. Chemical Kinetics and Reaction Mechanisms, 2nd ed.; McGraw-Hill: New York, 1995.
59. A single report indicates that the elimination of LiCl from 2-chloro-3-dimethylamino-6-phenylsulfonylphenyllithium is a first-order process: Zieger, H. E.; Wittig, G. J. Org. Chem. 1962, 27, 3270.
60. We define the idealized rate law as that obtained by rounding the observed reaction orders to the nearest rational order.
61. Frisch, M. J.; et al. Gaussian 03, revision B.04; Gaussian, Inc.: Pittsburgh, PA, 2003.
62. For related B3LYP computations of aryllithiums, see: (a) Wiberg, K. B.; Sklenak, S.; Bailey, W. F. J. Org. Chem. 2000, 65, 2014.
63. (b) Kremer, T.; Junge, M.; Schleyer, P. v. R. Organometallics 1996, 15, 3345. See also ref 10a.
64. (a) Li-F contacts have been found with ab initio calculations and associated to the formation of benzyne: Streitwieser, A. Abu-Hasanyan, F.; Neuhaus, A.; Brown, F. J. Org. Chem. 1996, 61, 3151.
65. (b) DFT computations indicate that Li-F interactions are stronger than Li-Cl contacts and control structure and solvation of carbenoid precursors: Pratt, L. M.; Ramachandran, B.; Xidos, J. D.; Cramer, C. J.; Truhlar, D. G. J. Org. Chem. 2002, 67, 7607.
66. (c) For a discussion on anti-MeO-Li interactions, see: Bauer, W.; Schleyer, P. v. R. J. Am. Chem. Soc. 1989, 111, 7191.
67. 3, see: (a) Krasovsky, A.; Straub, B. F.; Knochel, P. Angew. Chem., Int. Ed. 2006, 45, 159.
68. (ii) For computational discussions of lithiated benzenes, see: (b) Bachrach, S. M.; Chamberlin, A. C. J. Org. Chem. 2004, 69, 2111.
69. (c) Kwon, O.; Sevin, F.; McKee, M. L. J. Phys. Chem. A 2001, 105, 913.
70. For a discussion of the ortho-substituent effect on reducing solvent access to halophenylcesiums, see: Streitwieser, A. Abu-Hasanyan, F.; Neuhaus, A.; Brown, F. J. Org. Chem. 1996, 61, 3151.
71. Recent example of a small positive ΔG for the third solvation of an organolithium monomer calculated using DFT: Pratt, L. M.; Mu, R.; Jones, D. R. J. Org. Chem. 2005, 70, 101.
72. (i) Examples of a large positive AC for the third solvation of an organolithium monomer calculated using DFT: (a) Zuend, S. J.; Ramirez, A.; Lobkovsky, E.; Collum, D. B. J. Am. Chem. Soc. 2006, 128, 13753.
73. (b) Mogali, S.; Darville, K.; Pratt, L. M. J. Org. Chem. 2001, 66, 2368.
74. (ii) For a discussion on the limitations of DFT microsolvation models in organolithium chemistry, see: (c) Pratt, L. M.; Mogali, S.; Glinton, K. J. Org. Chem. 2003, 68, 6484.
75. 3(PhLi) = -9.3.
76. Carlqvist, P.; Östmark, H.; Brinck, T. J. Org. Chem. 2004, 69, 3222.
77. (a) Fressigné, C.; Lautrette, A.; Maddaluno, J. J. Org. Chem. 2005, 70, 7816.
78. (b) Pomelli, C. S.; Bianucci, A. M.; Crotti, P.; Favero, L. J. Org. Chem. 2004, 69, 150.
79. (c) Gillies, M. B.; Tønder, J. E.; Tanner, D.; Norrby, P. J. Org. Chem. 2002, 67, 7378.
80. (d) Fressigné, C.; Maddaluno, J.; Marquez, A.; Giessner-Prettre, C. J. Org. Chem. 2000, 65, 8899.
81. (a) Saunders, W. H., Jr.; Cockerill, A. F. Mechanisms of Elimination Reactions; John Wiley & Sons: New York, 1973; Vol. II, pp 60-68.
82. (b) Baciocchi, E. In The Chemistry of Halides, Pseudo Halides and Azides, Supplement D; Patai, S., Rappoport, Z., Eds.; Wiley: Chichester, U. K., 1983.
83. Theoretical studies of benzyne-halide ion complexes: (a) Morgon, N. H. J. Phys. Chem. 1995, 99, 17832.
84. (b) Wong, M. W. J. Chem. Soc., Chem. Commun. 1995, 2227.
85. (c) Linnert, H. V.; Riveros, J. M. J. Chem. Soc., Chem. Commun. 1993, 48.
86. As the C(2)-halide bond was lengthened, achieving wave function convergence became more difficult, a common limitation of DFT calculations.
87. LiCl) = +17.3, ΔG(7) = +15.1, ΔG(8) = +35.6, ΔG(9) = +8.9, ΔG(10) = +26.5.
88. De la Lande, A.; Fressigné, C.; Gérard, H.; Maddaluno, J.; Parisei, O. Chem. - Eur. J. 2007, 13, 3459.
89. (i) Reports of facile formation of benzyne from a 2-halo-6- methoxyaryllithiums: (a) Dabrowski, M.; Kubicka, J.; Lulinski, S.; Serwatowski, J. Tetrahedron Lett. 2005, 46, 4175.
90. (b) Barluenga, J.; Fañanás, F. J.; Sanz, R.; Fernández, Y. Chem. - Eur. J. 2002, 8, 2034.
91. (c) Slocum, D. W.; Dietzel, P. Tetrahedron Lett. 1999, 40, 1823.
92. (d) Iwao, M. J. Org. Chem. 1990, 55, 3622.
93. (e) Adejare, A.; Miller, D. D. Tetrahedron Lett. 1984, 25, 5597.
94. (ii) For the role of the ortho-substituent on the stabilization of 2-haloaryllithiums toward benzyne formation, see: (f) Mongin, F.; Rebstock, A.-S.; Trécourt, F.; Quéguiner, G.; Marsais, F. J. Org. Chem. 2004, 69, 6766.
95. (g) Gohier, F.; Mortier, J. J. Org. Chem. 2003, 68, 2030.
96. For analogous results of shallow potentials during the evaluation of transition structures involving C-halogen lengthening, see: (a) Xie, J.; Feng, D.; Feng, S.; Zhang, J. Chem. Phys. 2006, 323, 185.
97. (b) Flock, M.; Marschner, C. Chem. - Eur. J. 2005, 11, 4635.
98. (c) Gronert, S.; Kass, S. R. J. Org. Chem. 1997, 62, 7991.
99. (d) Merrill, G. N.; Gronert, S.; Kass, S. R. J. Phys. Chem. A 1997, 101, 208.
100. For examples of preferential elimination of F versus Cl, see: (a) Bach, R. D.; Evans, J. C. J. Am. Chem. Soc. 1986, 108, 1374.
101. (b) Baciocchi, E.; Ruzziconi, R. J. Org. Chem. 1984, 49, 3395.
102. (c) Baciocchi, E.; Ruzziconi, R.; Sebastiani, G. V. J. Am. Chem. Soc. 1983, 105, 6114.
103. (d) Baciocchi, E.; Ruzziconi, R.; Sebastiani, G. V. J. Org. Chem. 1982, 47, 3237.
104. (e) Okuhara, K. J. Org. Chem. 1976, 41, 1487.
105. Kofron, W. G.; Baclawski, L. M. J. Org. Chem. 1976, 41, 1879.