Practical synthesis of optically active fluorine-substituted α-phenylethylamines by retardation of hydrogenolytic cleavage at benzylic position

Chemistry Letters

Volumn 33, Issue 11, 2004, Pages 1424-1425

  Kanai, Masatomi ^a   Yasumoto, Manabu ^a   Kuriyama, Yokusu ^a   Inomiya, Kenjin ^a   Katsuhara, Yutaka ^a   Higashiyama, Kimio ^b   Ishii, Akihiro ^a  

^a CENTRAL GLASS CO LTD   (Japan)

^b HOSHI UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA METHYLBENZYLAMINE; FLUORINE DERIVATIVE;

ANALYTIC METHOD; ARTICLE; CHEMICAL PROCEDURES; CHEMICAL REACTION; CHEMICAL STRUCTURE; HYDROGENOLYSIS; REACTION ANALYSIS; STEREOCHEMISTRY; STRUCTURE ANALYSIS; SUBSTITUTION REACTION; SYNTHESIS;

EID: 13544276476     PISSN: 03667022     EISSN: None     Source Type: Journal    
DOI: 10.1246/cl.2004.1424     Document Type: Article

References (17)

1. M. Kanai, M. Yasumoto, Y. Kuriyama, K. Inomiya, Y. Katsuhara, K. Higashiyama, and A. Ishii, Org. Lett., 5, 1007 (2003).
2. Regioselective hydrogenolysis of bis(α-methylbenzyl)amines having electron-donating groups has been already reported. a) G. Bringmann, J.-P. Geisler, T. Geuder, G. Kunkel, and L. Kinzinger, Liebigs Ann. Chem., 1990, 795. b) G. Bringmann and J.-P. Geisler, Tetrahedron Lett., 30, 317 (1989).
3. Regioselective hydrogenolysis of bis(α-methylbenzyl)amines having electron-donating groups has been already reported. a) G. Bringmann, J.-P. Geisler, T. Geuder, G. Kunkel, and L. Kinzinger, Liebigs Ann. Chem., 1990, 795. b) G. Bringmann and J.-P. Geisler, Tetrahedron Lett., 30, 317 (1989).
4. Optically active fluorine-substituted α-phenylethylamines have been regarded as important intermediates in development of medicines. a) H. Kurata, T. Kohama, K. Kono, and K. Kitayama, WO 02051396 (2002). b) A. G. Taveras, C. J. Aki, R. W. Bond, J. Chao, M. Dwyer, J. A. Ferreia, J. Chao, Y. Yu, J. J. Baldwin, B. Kaiser, G. Li, J. R. Merritt, K. H. Nelson, and L. L. Rokosz, WO 0208364 (2002). c) B. A. Mckittrick, G. Guo, Z. Zhu, and Y. Ye, WO 02051808 (2002).
5. Optically active fluorine-substituted α-phenylethylamines have been regarded as important intermediates in development of medicines. a) H. Kurata, T. Kohama, K. Kono, and K. Kitayama, WO 02051396 (2002). b) A. G. Taveras, C. J. Aki, R. W. Bond, J. Chao, M. Dwyer, J. A. Ferreia, J. Chao, Y. Yu, J. J. Baldwin, B. Kaiser, G. Li, J. R. Merritt, K. H. Nelson, and L. L. Rokosz, WO 0208364 (2002). c) B. A. Mckittrick, G. Guo, Z. Zhu, and Y. Ye, WO 02051808 (2002).
6. Optically active fluorine-substituted α-phenylethylamines have been regarded as important intermediates in development of medicines. a) H. Kurata, T. Kohama, K. Kono, and K. Kitayama, WO 02051396 (2002). b) A. G. Taveras, C. J. Aki, R. W. Bond, J. Chao, M. Dwyer, J. A. Ferreia, J. Chao, Y. Yu, J. J. Baldwin, B. Kaiser, G. Li, J. R. Merritt, K. H. Nelson, and L. L. Rokosz, WO 0208364 (2002). c) B. A. Mckittrick, G. Guo, Z. Zhu, and Y. Ye, WO 02051808 (2002).
7. Recently enantioselective reductions of enamide have been reported. a) M. J. Burk, Y. M. Wang, and J. R. Lee, J. Am. Chem. Soc., 118, 5142 (1996). b) F.-Y. Zhang, C.-C. Pai, and A. S. C. Chan, J. Am. Chem. Soc., 120, 5808 (1998). c) W. Hu, M. Yan, C.-P. Lau, S. M. Yang, and A. S. C. Chen, Tetrahedron Lett., 40, 973 (1999). d) Y.-Y. Yang and T. V. RajanBabu, Org. Lett., 2, 4137 (2000).
8. Recently enantioselective reductions of enamide have been reported. a) M. J. Burk, Y. M. Wang, and J. R. Lee, J. Am. Chem. Soc., 118, 5142 (1996). b) F.-Y. Zhang, C.-C. Pai, and A. S. C. Chan, J. Am. Chem. Soc., 120, 5808 (1998). c) W. Hu, M. Yan, C.-P. Lau, S. M. Yang, and A. S. C. Chen, Tetrahedron Lett., 40, 973 (1999). d) Y.-Y. Yang and T. V. RajanBabu, Org. Lett., 2, 4137 (2000).
9. Recently enantioselective reductions of enamide have been reported. a) M. J. Burk, Y. M. Wang, and J. R. Lee, J. Am. Chem. Soc., 118, 5142 (1996). b) F.-Y. Zhang, C.-C. Pai, and A. S. C. Chan, J. Am. Chem. Soc., 120, 5808 (1998). c) W. Hu, M. Yan, C.-P. Lau, S. M. Yang, and A. S. C. Chen, Tetrahedron Lett., 40, 973 (1999). d) Y.-Y. Yang and T. V. RajanBabu, Org. Lett., 2, 4137 (2000).
10. Recently enantioselective reductions of enamide have been reported. a) M. J. Burk, Y. M. Wang, and J. R. Lee, J. Am. Chem. Soc., 118, 5142 (1996). b) F.-Y. Zhang, C.-C. Pai, and A. S. C. Chan, J. Am. Chem. Soc., 120, 5808 (1998). c) W. Hu, M. Yan, C.-P. Lau, S. M. Yang, and A. S. C. Chen, Tetrahedron Lett., 40, 973 (1999). d) Y.-Y. Yang and T. V. RajanBabu, Org. Lett., 2, 4137 (2000).
11. Only regioselective hydrogenolysis of ortho-fluorine-substituted bis(α-methylbenzyl)amine has been reported to give a moderate regioselectivity of 89:11. However, its scope and limitation and effect of fluorine atom were not discussed at all. G. Bringmann and J.-P. Geisler, J. Fluorine Chem., 49, 67 (1990).
12. Diastereomeric mixtures of 1 were prepared through dehydration between corresponding fluorine-substituted acetophenones (100 mmol) and commercially available (S)-α-phenylethylamine (110 mmol), followed by reduction of resulting imines. Dehydration was performed in the presence of a catalytic amount of zinc chloride (1.00 mmol) in toluene (1 M) under reflux (15 h) with removal of produced water using a Dean-Stark trap in quantitative yields. Three m-, p-, and 3,5-di-F-imines were obtained solely as (E)-isomers, while o-F-imine contained a small amount of (Z)-isomer (E:Z = 85:15). Reduction was performed using sodium borohydride (100 mmol) in methanol (1 M) at 0°C (7h) in quantitative yields with moderate diastereomeric excesses [ca. 60-70% de (S,S) for m-, p-, and 3,5-diF-1], except for o-F-1 [20% de (S,S)]. Diastereomeric excesses of all bis(α-methylbenzyl)amines were easily improved to >99.5% (S,S) by recrystallization of phthalic acid salts in ca. 70% recovery yields.
13. Pd/C (NX-type, 5 wt %, water content 50 wt %, N. E. CHEM-CAT) was used.
14. R. Filler, in "Organofluorine Chemicals and Their Industrial Applications," ed. by R. E. Banks, Ellis Horwood, Ltd., Chichester, UK (1979), Chap. 6.
15. Diastereomeric excesses of 4-fluoro-4′-methyl- and 4-fluoro-4′-ethyl-disubstituted substrates (3 and 4) were 67% (S,S) and 66% (S,S), respectively.
16. Acetic acid (5.0 equiv.) was added.
17. 2 pressure at 60°C for 12 h. Pd catalyst was filtered off through a Celite pad, and after removal of solvent under a reduced pressure, residue was distilled (69°C/7 mmHg) to give 76.4 g (0.55 mol) of p-F-2 in 98% yield [GC purity = 99.9%, 99.7% ee, (S)].