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Enzyme Promiscuity as a Remedy for the Common Problems with Knoevenagel Condensation
Author(s) -
Koszelewski Dominik,
Ostaszewski Ryszard
Publication year - 2019
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201901491
Subject(s) - knoevenagel condensation , aldehyde , chemistry , lipase , enol , cascade reaction , catalysis , hydrolysis , tandem , combinatorial chemistry , methylene , organic chemistry , enzyme catalysis , active site , enzyme , condensation reaction , materials science , composite material
A new protocol based on lipase‐catalyzed tandem reaction toward α,β‐enones/enoesters is presented. For the synthesis of the desired products the tandem process based on enzyme‐catalyzed hydrolysis and Knoevenagel reaction starting from enol acetates and aldehyde is developed. The relevant impact of the reaction conditions including organic solvent, enzyme type, and temperature on the course of the reaction was revealed. It was shown that controllable release of the active methylene compound from the corresponding enol carboxylate ensured by enzymatic reaction diminishes significantly the formation of the unwanted co‐products. Furthermore, this protocol was extended by including a second tandem chemoenzymatic transformation engaging various aldehyde precursors. After a careful optimization of the reaction conditions, the target products were obtained with yields up to 86 % and with excellent E / Z ‐selectivity.