Asymmetric Synthesis of Bicyclic Diol Derivatives through Metal and Enzyme Catalysis: Application to the Formal Synthesis of Sertraline |
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Authors: | Patrik Krumlinde Krisztián Bogár Dr Jan‐E Bäckvall Prof |
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Institution: | 1. Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, 106?91 Stockholm (Sweden), Fax: (+46)?8‐15‐49‐08;2. Medicinal Chemistry Discovery, AstraZeneca R&D, 151?85 S?dert?lje (Sweden) |
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Abstract: | Enzyme‐ and ruthenium‐catalyzed dynamic kinetic asymmetric transformation (DYKAT) of bicyclic diols to their diacetates was highly enantio‐ and diastereoselective to give the corresponding diacetates in high yield with high enantioselectivity (99.9 % ee). The enantiomerically pure diols are accessible by simple hydrolysis (NaOH, MeOH), but an alternative enzyme‐catalyzed ester cleavage was also used to give the trans‐diol (R,R)‐ 1 b in extremely high diastereomeric purity (trans/cis=99.9:0.1, >99.9 % ee). It was demonstrated that the diols can be selectively oxidized to the ketoalcohols in a ruthenium‐catalyzed Oppenauer‐type reaction. A formal enantioselective synthesis of sertraline from a simple racemic cis/trans diol 1 b was demonstrated. |
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Keywords: | alcohols asymmetric catalysis dynamic resolution enzyme catalysis metal catalysis |
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