Enantioselective Michael Addition of the 2‐(1‐Ethylpropoxy)acetaldehyde to N‐[(1Z)‐2‐Nitroethenyl]acetamide – Optimization of the Key Step in the Organocatalytic Oseltamivir Synthesis |
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| Authors: | Viktória Hajzer Attila Latika Július Durmis Radovan Šebesta |
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| Institution: | 1. Synkola, Mlynská dolina CH‐2, SK‐84215 Bratislava, Slovakia;2. Department of Organic Chemistry, Faculty of Natural Sciences, Comenius University in Bratislava, Mlynská dolina CH‐2, SK‐84215 Bratislava (phone: +421‐2‐60296208;3. fax: +421‐2‐60296337) |
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| Abstract: | Organocatalytic Michael addition of alkoxyacetaldehyde 1 to N‐protected 2‐nitroethene‐1‐amine 2 (Scheme 2) is a key step in the synthesis of an important antiviral agent, oseltamivir. Screening of a large array of structurally diverse acids as potential promoters led to the identification of several useful acidic additives for this reaction (Tables 1–4). Also other reaction parameters were investigated with the aim of improving the diastereoselectivity of the Michael addition, while maintaining high enantiomer purity and yield (Tables 5 and 6). |
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| Keywords: | Oseltamivir Enantioselective synthesis Antiviral activity Organocatalysis Michael addition |
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