Generation and suppression of 3-/4-functionalized benzynes using zinc ate base (TMP-Zn-ate): New approaches to multisubstituted benzenes

Journal of the American Chemical Society

Volumn 130, Issue 2, 2008, Pages 472-480

  Uchiyama, Masanobu ^a,b,c   Kobayashi, Yuri ^a   Furuyama, Taniyuki ^a,c   Nakamura, Shinji ^a   Kajihara, Yumiko ^b   Miyoshi, Tomoko ^b   Sakamoto, Takao ^b   Kondo, Yoshinori ^b   Morokuma, Keiji ^d  

^a UNIVERSITY OF TOKYO   (Japan)

^b TOHOKU UNIVERSITY   (Japan)

^c INST OF PHYS AND CHEMICAL RESEARCH   (Japan)

^d EMORY UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BENZENE; DEPROTONATION; DERIVATIVES; NUCLEOPHILES; REGIOSELECTIVITY;

FUNCTIONALIZED BENZYNES; ZINCATION;

ZINC COMPOUNDS;

ALKADIENE; BASE; BENZENE DERIVATIVE; HALOGEN; PIPERIDINE DERIVATIVE; ZINC DERIVATIVE; LITHIUM DERIVATIVE; ZINC;

ARTICLE; CHEMICAL MODEL; ENZYME SUBSTRATE; LIGATION; METHODOLOGY; PROTON TRANSPORT; SUBSTITUTION REACTION; SYNTHESIS; CHEMISTRY;

BENZENE DERIVATIVES; HALOGENS; LITHIUM COMPOUNDS; ZINC;

EID: 40149108668     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja071268u     Document Type: Article

References (60)

1. (a) Knochel, P. In Comprehensive Organic Synthesis; Trost, B. M., Ed.; Pergamon Press: Oxford,England, 1991; Vol. 8, Chapter 4.4 and references cited therein.
2. (b) Kessar, S. V. In Comprehensive Organic Synthesis; Trost, B. M., Ed.; Pergamon Press: Oxford, England, 1991; Vol. 8, Chapter 2.3 and references cited therein.
3. (a) Johnson, W. T. G.; Cramer, C. J. J. Am. Chem. Soc. 2001, 123, 923-928.
4. (b) Dkhar, P. G. S.; Lyngdoh, R. H. D. Proc. Indian Acad. Sci., Chem. Sci. 2000, 112, 97-108 (CAN 133:104683).
5. (a) Hoffmann, R. W. Dehydrobenzene and Cycloalkynes: Academic Press: New York, 1967.
6. (b) H. Hart. In The Chemistry of Triple-Bonded Functional Groups; S. Patai, Ed.; John Wiley & Sons Ltd.: Chichester, U.K., 1994; Suppl. C2, Chapter 18.
7. (c) Gilchrist, T. L. In The Chemistry of Functional Groups; Patai, S., Rappoport, Z., Eds.; Wiley: Chichester, U.K., 1983; Suppl. C, Chapter 11.
8. For examples of the preparation of benzynes, see: (d) Kitamura, T.; Yamane, M.; Inoue, K.; Tokuda, M.; Fukatsu, N.; Meng, Z.; Fujiwara, Y. J. Am. Chem. Soc. 1999, 121, 11674-11679.
9. (e) Matsumoto, T.; Hosoya, T.; Katsuki, M.; Suzuki, K. Tetrahedron. Lett. 1991, 32, 6735-6736.
10. (f) Liu, Z.; Larock, R. C. Org. Lett. 2004, 6, 99-102.
11. A part of the results concerning the 3-functionalized benzynes described here was reported as a preliminary Communication: Uchiyama, M.; Miyoshi, T.; Kajihara, Y.; Sakamoto, T.; Otani, Y.; Ohwada, T.; Kondo, Y. J. Am. Chem. Soc. 2002, 124, 8514-8515.
12. For reviews on directed ortho metalation, see; (a) Snieckus, V. Chem. Rev. 1990, 90, 879-933.
13. (b) Gschwend, H. W.; Rodriguez, H. R. Heteroat. Facilitated Lithiations. Org. React. (NY.) 1979, 26, 1-360.
14. For examples of nonlithio-aromatic species, see: (a) Armstrong, D. R.; Clegg, W.; Dale, S. H.; Hevia, E.; Hogg, L. M.; Honeyman, G. W.; Mulvey, R. E. Angew. Chem., Int. Ed. 2006, 45, 3775-3778.
15. (b) Sapountzis, I.; Lin, W.; Fischer, M.; Knochel, P. Angew. Chem., Int. Ed. 2004, 43, 4364-4366.
16. Upton, C. J.; Beak, P. J. Org. Chem. 1975, 40, 1094-1098.
17. (a) Review: Uchiyama, M.; Kondo, Y. Synth. Org. Chem. Jpn. 2006, 64, 1180-1190.
18. (b) Kondo, Y.; Takazawa, N.; Yamazaki, C.; Sakamoto, T. J. Org. Chem. 1994, 59, 4717-4718.
19. (c) Kondo, Y.; Matsudaira, T.; Sato, J; Murata, N.; Sakamoto, T. Angew. Chem., Int. Ed. Engl. 1996, 35, 736-738.
20. (d) Kondo, Y.; Fujinami, M.; Uchiyama, M.; Sakamoto, T. J. Chem. Soc., Perkin Trans. 1 1997, 799-800.
21. Harada, T.; Chiba, M.; Oku, A. J. Org. Chem. 1999, 64, 8210-8213.
22. 3ZnLi was performed under reflux for 16 hours in the presence of diene (A), the Diels-Alder adduct (4a) was obtained in 50% yield.
23. (a) Uchiyama, M.; Furuyama, T.; Kobayashi, M.; Matsumoto, Y.; Tanaka, K. J. Am. Chem. Soc. 2006, 128, 8404-8405.
24. (b) Uchiyama, M.; Matsumoto, Y.; Nakamura, S.; Ohwada, T.; Kobayashi, N.; Yamashita, N.; Matsumiya, A.; Sakamoto, T. J. Am. Chem. Soc., 2004, 126, 8755-8758.
25. (c) Uchiyama, M.; Kondo, Y.; Miura, T.; Sakamoto, T. J. Am. Chem. Soc. 1997, 119, 12372-12373.
26. (d) Uchiyama, M.; Koike, M.; Kameda, M.; Kondo, Y.; Sakamoto, T. J. Am. Chem. Soc. 1996, 118, 8733-8734.
27. 2Zn(TMP)Li is endothermic in most cases, so excess zincate (2.2 equiv) was used for the deprotonation reaction in this study. Iodine or benzaldehydc was used as a representative electrophile in this study, but intermediary arylzincate species are known to be able to react with various electrophiles (see refs 8, 11, and 14).
28. A series of recent studies has expanded the utility of rigid oxabicyclic compounds: (a) Lautens, M.; Hiebert, S. J. Am. Chem. Soc. 2004, 126, 1437-1447.
29. (b) Lautens, M.; Fagnou, K.; Yang, D. J. Am. Chem. Soc. 2003, 125, 14884-14892.
30. (c) Lautens, M.; Fagnou, K.; Hiebert, S. J. Am. Chem. Soc. 2003, 125, 48-58.
31. (d) Lautens, M.; Schmid, G. A.; Chau, A. J. Org. Chem. 2002, 67, 8043-8053.
32. (e) Lautens, M.; Hiebert, S.; Renaud, J-L. J. Am. Chem. Soc. 2001, 123, 6834-6839.
33. (f) Lautens, M.; Fagnou, K. J. Am. Chem. Soc. 2001, 123, 7170-7171.
34. (g) Lautens, M.; Renaud, J-L.; Hiebert, S. J. Am. Chem. Soc. 2000, 122, 1803-1804.
35. (a) Kondo, Y.; Shilai, M.; Uchiyama, M.; Sakamoto, T. J. Am. Chem. Soc. 1999, 121, 3539-3540.
36. (b) Imahori, T.; Uchiyama, M.; Sakamoto, T.; Kondo, Y. Chem. Commun. 2001, 2450-2451.
37. (c) Uchiyama, M.; Matsumoto, Y.; Nobuto, D.; Furuyama, T.; Yamaguchi, K.; Morokuma, K. J. Am. Chem. Soc. 2006, 128, 8748-8750.
38. (d) Uchiyama, M.; Matsumoto, Y.; Usui, S.; Hashimoto, Y.; Morokuma, K. Angew. Chem., Int. Ed. 2007, 46, 926-929.
39. (e) Mulvey, R. E.; Mongin, F.; Uchiyama, M.; Kondo, Y. Angew. Chem., Int. Ed. 2007, 46, 3802-3824.
40. (f) Kondo, Y.; Morey, J. V.; Morgan, J. C.; Naka, H.; Nobuto, D.; Raithby, P. R.; Uchiyama, M.; Wheatley, A. E. H. J. Am. Chem. Sol. 2007, 129, ASAP.
41. The iodine-zinc exchange may occur preferentially over the deprotonation.
42. Generally, when traditional reagents, such as alkyllithiums and lithium amides, are used, the desired 1,2,3-trisubstituted benzene derivatives are not obtained in high yields under usual conditions because of the instability of these reagents and/or intermediary aryllithium species widi various electrophilic substituents or neighboring bromine (including the formation of benzyne). Indeed, the 2,6-disubstituted iodobenzene derivatives shown in Table 3 are all new compounds.
43. 2Zn(TMP)Li under similar reaction conditions, 8a was also obtained as a single product. (Chemical Equation Presented)
44. For review see: Reuman, M.; Meyers, A. I. Tetrahedron 1985, 41, 837-860.
45. (a) Nakamura, S.; Uchiyama, M. J. Am. Chem. Soc. 2007, 129, 28-29,
46. (b) Nakamura, S.; Uchiyama, M.; Ohwada, T. J. Am. Chem. Soc. 2005, 127, 13116-13117.
47. (c) Nakamura, S.; Uchiyama, M.; Ohwada, T. J. Am. Chem. Soc. 2004, 126, 11146-11147.
48. Comparison of the relative energies of the intermediary zincates based on MP2/631SVPs calculation. (See Computational Methods for details) (Chemical Equation Presented)
49. When THF was used as a solvent, the yield of 12a was reduced, though no non-methylated protonation product could be detected.
50. Frisch, M. J.; et al. Gaussian 03, revision B.04; Gaussian, Inc.: Pittsburgh, PA, 2003.
51. Møller, C.; Plesset, M. S. Phys. Rev. 1934, 46, 618-622.
52. Schäfer, A.; Horn, H.; Ahlrichs, R. J. Chem. Phys. 1992, 97, 2571-2577.
53. (a) Fukui, K. Acc. Chem. Res. 1981, 14, 363-368.
54. (b) Gonzalez, C.; Schlegel, H. B. J. Chem. Phys. 1989, 90, 2154-2161.
55. Gonzalez, C.; Schlegel, H. B. J. Phys. Chem. 1990, 94, 5523-5527.
56. (a) Kwon, O.; Mckee, M. L. J. Phys. Chem. A 2001, 105, 10133-10138.
57. (b) Irle, S.; Rubin, Y.; Morokuma, K. J. Phys. Chem. A 2002, 106, 680-688.
58. We identified another complexes CP2 in which a benzyne and the zincate coordinate through cation-p (benzyne; exocyclic p bond) interaction. The energy difference between CP1 and CP2 is only 1.2 kcal/mol and hence they may be in equilibrium.
59. Retbøll, M.; Edwards, A. J.; Rae, A. D.; Willis, A. C.; Bennett, M. A.; Wenger, E. J. Am. Chem. Soc. 2002, 124, 8348-8360.
60. García-Cuadrado, D.; Braga, A. A. C.; Maseras, F.; Echavarren, A. M. J. Am. Chem. Soc. 2006, 128, 1066-1067.