Asymmetric hydrogenation of beta-amino ketones with the bimetallic complex RuPHOX-Ru as the chiral catalyst

作者：Wang, Jiahao; Liu, Delong^*; Liu, Yangang; Zhang, Wanbin

来源：Organic and Biomolecular Chemistry, 2013, 11(23): 3855-3861.

DOI：10.1039/c3ob40135a

• ENANTIOMERICALLY PURE NORFLUOXETINE
• ALLYLIC ALKYLATION
• ENANTIOSELECTIVE HYDROGENATION
• DIPHOSPHINE LIGANDS
• PRACTICAL SYNTHESIS
• METAL-COMPLEXES
• S-FLUOXETINE
• (R)-FLUOXETINE HYDROCHLORIDE
• OXAZABOROLIDINE CATALYST
• DIHYDROXYLATION ROUTE

Asymmetric hydrogenations of a series of beta-amino ketones were carried out with a bimetallic complex (RuPHOX-Ru) as the chiral catalyst. Almost all the reactions (performed in a mixed solvent system of toluene and H2O in the presence of KOH) gave quantitative conversions into their respective products with up to 99.9% ee. The RuPHOX-Ru catalyst is stable to both moisture and air. The procedure has the benefits of being inexpensive, environmentally friendly and highly efficient. Under a relatively low catalyst loading (TON = 2000), key intermediates of fluoxetine, tomoxetine and nisoxetine could be obtained in quantitative yield and in up to 99.9% ee. This methodology represents a promising alternative to the synthesis of the aforementioned drugs and their analogues.

• 出版日期2013
• 单位上海交通大学