Cis‐4‐Alkoxydialkyl‐ andcis‐4‐Alkoxydiarylprolinol Organocatalysts: High Throughput Experimentation (HTE)‐Based and Design of Experiments (DoE)‐Guided Development of a Highly Enantioselectiveaza‐Michael Addition of Cyclic Imides to α, β‐Unsaturated Aldehydes. Issue 14 (6th April 2017)

• Record Type: Journal Article
• Authors: Arenas, Ismael; Ferrali, Alessandro; Rodríguez‐Escrich, Carles; Bravo, Fernando; Pericàs, Miquel A.
• Is Part Of: Advanced synthesis & catalysis. Volume 359:Issue 14(2017)
• Page Start: 2414
• Page End: 2424
• Publication Date: 2017-04-06
• Subjects: design of experiments -- diarylprolinol catalysts -- high throughput experimentation -- organocatalysis; Catalysis -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Chemistry -- Periodicals; Chemistry, Technical -- Periodicals; Chemistry -- Periodicals; Catalysis -- Periodicals; Technology, Pharmaceutical -- Periodicals; 547.2
• DOI: 10.1002/adsc.201700120
• Languages: English
• ISSNs: 1615-4150

Abstract

Abstract: 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. Abstract :