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Enantioselective Michael Addition of the 2‐(1‐Ethylpropoxy)acetaldehyde to N ‐[(1 Z )‐2‐Nitroethenyl]acetamide – Optimization of the Key Step in the Organocatalytic Oseltamivir Synthesis
Author(s) -
Hajzer Viktória,
Latika Attila,
Durmis Július,
Šebesta Radovan
Publication year - 2012
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.201200527
Subject(s) - chemistry , michael reaction , enantioselective synthesis , amine gas treating , acetamide , yield (engineering) , combinatorial chemistry , enantiomer , acetaldehyde , organic chemistry , catalysis , stereochemistry , materials science , metallurgy , ethanol
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 ).