Novel and enantioselective syntheses of (R)- and (S)-3-hydroxy-4-(2,4,5- trifluorophenyl)butanoic acid: A synthon for sitagliptin and its derivatives


Fistikci M., Gundogdu O., Aktas D., SEÇEN H., Sahin M. F., Altundas R., ...Daha Fazla

Tetrahedron, cilt.68, sa.12, ss.2607-2610, 2012 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 68 Sayı: 12
  • Basım Tarihi: 2012
  • Doi Numarası: 10.1016/j.tet.2012.01.095
  • Dergi Adı: Tetrahedron
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.2607-2610
  • Anahtar Kelimeler: (R)- and (S)-3-Hydroxy-4-(2,4,5-trifluorophenyl)butanoic acid, Aminoxylation, d- andl-Proline, Sitagliptin
  • Hakkari Üniversitesi Adresli: Hayır

Özet

A new synthetic strategy for (R)- and (S)-3-hydroxy-4-(2,4,5- trifluorophenyl)butanoic acid, a building block in the preparation of sitagliptin and its derivatives, was developed. Pd(OAc) 2 catalyzed coupling of 2,4,5-trifluoro-1-iodobenzene with allyl alcohol gave 3-(2,4,5-trifluorophenyl)propanal in a yield of 95%. l-Proline catalyzed reaction of the 3-phenylpropanal (in only 1.2 molar equiv) with nitrosobenzene followed by reduction with NaBH 4 and Pd/C catalyzed hydrogenation gave (R)-3-(2,4,5-trifluorophenyl)propane-1,2-diol with >99% ee and 65% yield. Selective tosylation of primary hydroxyl group of the 1,2-propandiol unit followed by cyanide displacement afforded (R)-3-hydroxy-4-(2,4,5- trifluorophenyl)butanenitrile (80%). The nitrile was converted to the title β-hydroxy acid under basic hydrolysis in a yield of 90%. Thus, (R)-3-hydroxy-4-(2,4,5-trifluorophenyl)butanoic acid was prepared enantioselectively from the starting material in four steps and 45% overall yield. The reaction sequence was repeated with d-proline as the catalyst to give (S)-3-hydroxy-4-(2,4,5-trifluorophenyl)butanoic acid in 45% overall yield and >99% enantiomeric excess. © 2012 Elsevier Ltd. All rights reserved.