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cis ‐4‐Alkoxydialkyl‐ and cis ‐4‐Alkoxydiarylprolinol Organocatalysts: High Throughput Experimentation (HTE)‐Based and Design of Experiments (DoE)‐Guided Development of a Highly Enantioselective aza ‐Michael Addition of Cyclic Imides to α,β‐Unsaturated Aldehydes
Author(s) -
Arenas Ismael,
Ferrali Alessandro,
RodríguezEscrich Carles,
Bravo Fernando,
Pericàs Miquel A.
Publication year - 2017
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201700120
Subject(s) - enantiopure drug , maleimide , succinimide , chemistry , enantioselective synthesis , michael reaction , organocatalysis , adduct , catalysis , organic chemistry , addition reaction , combinatorial chemistry
A diverse family (37 compounds) of cis ‐4‐alkoxydiorganylprolinol derivatives has been prepared and evaluated in organocatalysis for the first time. The combined use of high throughput experimentation (HTE) techniques with efficient analytical methods has led to the identification of two superior catalysts for the enantioselective addition of succinimide to α,β‐unsaturated aldehydes. Further optimization of the reaction conditions with design of experiments (DoE) techniques established the catalyst of choice for the considered aza ‐Michael reaction, the corresponding adducts (12 examples) being obtained in good yields and excellent enantioselectivities (succinimide and maleimide donors). The synthetic versatility of these Michael adducts is illustrated by a two‐step sequence leading to enantiopure 1,3‐amino alcohols.