Open AccessSynthesis of Optically Active syn- and anti-Chlorohydrins through a Bienzymatic Reductive Cascade
Author(s) -
Jorge González-Rodríguez,
Jesús Albarrán-Velo,
Raquel G. Soengas,
Iván Lavandera,
Vicente GotorFernández,
Humberto RodríguezSolla
Publication year - 2022
Publication title -
organic letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.94
H-Index - 239
eISSN - 1523-7060
pISSN - 1523-7052
DOI - 10.1021/acs.orglett.2c02592
Subject(s) - enantiopure drug , chemistry , diastereomer , optically active , isomerization , enantiomer , alcohol , enantiomeric excess , aldehyde , cascade , catalysis , organic chemistry , enantioselective synthesis , stereochemistry , chromatography
A bienzymatic cascade has been designed and optimized to obtain enantiopure chlorohydrins starting from the corresponding 1-aryl-2-chlorobut-2-en-1-ones. For the synthesis of these α-chloroenones, a two-step sequence was developed consisting of the allylation of the corresponding aldehyde with 3-dichloroprop-1-ene, followed by oxidation and further isomerization. The selective cooperative catalytic system involving ene-reductases (EREDs) and alcohol dehydrogenases (ADHs) afforded the desired optically active chlorohydrins under mild reaction conditions in excellent conversions (up to >99%) and selectivities (up to >99:1 diastereomeric ratio (dr), >99% enantiomeric excess ( ee )).