A practical synthesis of (S)-oxybutynin

Tetrahedron Letters

Volumn 43, Issue 48, 2002, Pages 8647-8651

  Masumoto, Shuji ^a   Suzuki, Masato ^a   Kanai, Motomu ^a,b   Shibasaki, Masakatsu ^a  

^a UNIVERSITY OF TOKYO   (Japan)

^b JAPAN SCIENCE AND TECHNOLOGY AGENCY   (Japan)

Author keywords

hydroxy carboxylic acid; Catalytic enantioselective cyanosilylation; Ketones; Muscarinic receptor antagonist; Oxybutynin; Practical synthesis

Indexed keywords

ALPHA HYDROXY CARBOXYLIC ACID; CARBOXYLIC ACID DERIVATIVE; CYANOHYDRIN; DEUTERIUM; KETONE DERIVATIVE; MUSCARINIC RECEPTOR BLOCKING AGENT; OXYBUTYNIN; UNCLASSIFIED DRUG;

ARTICLE; CATALYSIS; CATALYST; DRUG SYNTHESIS; ENANTIOMER; ENANTIOSELECTIVITY; SILYLATION;

EID: 0037175497     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(02)02135-4     Document Type: Article

References (20)

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7. For other examples of catalytic enantioselective cyanosilylation of ketones, see: (a) Tian, S.-K.; Deng, L. J. Am. Chem. Soc. 2001, 123, 6195-6196; (b) Belokon', Y. N.; Green, B.; Ikonnikov, N. S.; North, M.; Parsons, T.; Tararov, V. I. Tetrahedron 2001, 57, 771-779; (c) Deng, H.; Isler, M. P.; Snapper, M. L.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2002, 41, 1009-1012.
8. For other examples of catalytic enantioselective cyanosilylation of ketones, see: (a) Tian, S.-K.; Deng, L. J. Am. Chem. Soc. 2001, 123, 6195-6196; (b) Belokon', Y. N.; Green, B.; Ikonnikov, N. S.; North, M.; Parsons, T.; Tararov, V. I. Tetrahedron 2001, 57, 771-779; (c) Deng, H.; Isler, M. P.; Snapper, M. L.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2002, 41, 1009-1012.
9. For other examples of catalytic enantioselective cyanosilylation of ketones, see: (a) Tian, S.-K.; Deng, L. J. Am. Chem. Soc. 2001, 123, 6195-6196; (b) Belokon', Y. N.; Green, B.; Ikonnikov, N. S.; North, M.; Parsons, T.; Tararov, V. I. Tetrahedron 2001, 57, 771-779; (c) Deng, H.; Isler, M. P.; Snapper, M. L.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2002, 41, 1009-1012.
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12. The absolute configuration of 7a was determined to be (S) after conversion to carboxylic acid 8 and by a comparison of the optical rotation with the reported value (Ref. 3a ). This is the same enantioselectivity as with other previously studied simple ketones such as acetophenone, suggesting that the catalyst recognizes the cyclohexyl group as a smaller group than the phenyl.
13. The (R)-selective titanium complex could not promote the reaction from 6a at low temperature. The reaction proceeded at room temperature and (R)-7a was obtained in 96% yield with only 7% ee (36 h). For the (R)-selective catalytic cyanosilylation of ketones, see: Hamashima Y., Kanai M., Shibasaki M. J. Am. Chem. Soc. 122:2000;7412-7413.
14. This procedure was the representative one previously (Ref. 4 ).
15. For the conversion of 8 to 1, see: Bakale, R. P.; Lopez, J. L.; McConville, F. X.; Vandenbossche, C. P.; Senanayake, C. H. US Pat. 6,140,529.
16. Molecular modeling studies indicated that 6e contains similar conformation and electronic character with other ketones.
17. A facile equilibrium followed by a kinetic resolution through an enantioselective silylation might be another possible pathway, however this possibility was also excluded based on the experiments described in the text. The related mechanism was proposed in Deng's catalytic enantioselective cyanosilylation of ketones (Ref. 5a ).
18. In the absence of the catalyst precursor 11, the silylation of the ketone cyanohydrins with TMSCN was very sluggish.
19. For the use of an isotope effect in organic synthesis to prevent the undesired deprotonation, see: (a) Dudley, G. B.; Danishefsky, S. J.; Sukenick, G. Tetrahedron Lett. 2002, 43, 5605-5606; (b) Vedejs, E.; Little, J. J. Am. Chem. Soc. 2002, 124, 748-749.
20. For the use of an isotope effect in organic synthesis to prevent the undesired deprotonation, see: (a) Dudley, G. B.; Danishefsky, S. J.; Sukenick, G. Tetrahedron Lett. 2002, 43, 5605-5606; (b) Vedejs, E.; Little, J. J. Am. Chem. Soc. 2002, 124, 748-749.