Enantioselective synthesis of ethyl nipecotinate using cinchona modified heterogeneous catalysts

✍ Scribed by H.-U Blaser; H Hönig; M Studer; C Wedemeyer-Exl

• Publisher: Elsevier Science
• Year: 1999
• Tongue: English
• Weight: 81 KB
• Volume: 139
• Category: Article
• ISSN: 1381-1169
• DOI: 10.1016/s1381-1169(98)00200-3

✦ Synopsis

Ethyl nicotinate was hydrogenated to ethyl nipecotinate in two steps. In the first step, the starting material was converted to the 1,4,5,6-tetrahydro derivative with PdrC and hydrogen in 76% yield. The hydrogenation of this intermediate was investigated with both unmodified and 10,11-dihydrocinchonidine modified noble metal catalysts and the influence of the catalyst metal, support, solvent and modifier concentration was tested. Catalyst activity was low in all cases, probably because the C5C double bond is part of a vinylogeous carbamate. The highest activity was observed with Rh and RhrPt Ž . catalysts. Highest ee's were obtained at relatively low conversions with PdrC in DMF 19% ee, 12% conversion and Ž . PdrTiO in a DMFrH OrAcOH system 24% ee, 10% conversion . This is the first successful example of an 2 2 enantioselection in the hydrogenation of an a ,b-unsaturated ester with a modified heterogeneous catalyst. With the addition of 10,11-dihydrocinchonidine, catalyst activity usually decreased. Ee and activity were strongly influenced by the catalyst metal, the carrier and the solvent. Due to the empiric nature of the study and the low ee's obtained, a mechanistic interpretation of the results is not warranted.