Additives Promote Noyori-type Reductions of a 尾-Keto-纬-lactam: Asymmetric Syntheses of Serotonin Norepinephrine Reuptake Inhibitors
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- 作者：Nicholas A. Magnus ; Bret A. Astleford ; Dana L. T. Laird ; Todd D. Maloney ; Adam D. McFarland ; John R. Rizzo ; J. Craig Ruble ; Gregory A. Stephenson ; James P. Wepsiec
- 刊名：The Journal of Organic Chemistry
- 出版年：2013
- 出版时间：June 7, 2013
- 年：2013
- 卷：78
- 期：11
- 页码：5768-5774
- 全文大小：341K
- 年卷期：v.78,no.11(June 7, 2013)
- ISSN：1520-6904
文摘
Serotonin norepinephrine reuptake inhibitor (SNRI) pyrrolidinyl ether 2 was synthesized by employing a dynamic kinetic resolution (DKR) with enantio- and diastereoselective hydogenation on 尾-keto-纬-lactam 8 to afford 尾-hydroxy-纬-lactam 9 with 96% ee and 94% de. Reduction of 9 and purification via the dibenzoyl-(l)-tartaric acid diastereomeric salt 16 enriched the ee and de to 100%. While screening hydrogenation reaction systems with ruthenium-BINAP catalysts to prepare 9, it was found that adding catalytic HCl and LiCl enabled higher yields. In addition, the rate and equilibrium of the DKR-hydrogenation of 8 to give 9 was studied by online NMR and chiral HPLC, which indicated that one of the enantiomers of 8 was reducing faster to 9 than the equilibration of the stereocenter of 8.