Acetaldehyde in the Enders triple cascade reaction via acetaldehyde dimethyl acetal

Beilstein J Org Chem. 2023 Aug 24:19:1243-1250. doi: 10.3762/bjoc.19.92. eCollection 2023.

Abstract

Asymmetric organocatalyzed multicomponent reactions represent an important toolbox in the field of organic synthesis to build complex scaffolds starting from simple starting materials. The Enders three-component cascade reaction was a cornerstone in the field and a plethora of organocatalyzed cascade reactions followed. However, acetaldehyde was not shown as a successful reaction partner, probably because of its high reactivity. Herein, we report the Enders-type cascade reaction using acetaldehyde dimethyl acetal, as a masked form of acetaldehyde. This strategy directly converts acetaldehyde, nitroalkenes and enals into stereochemically dense cyclohexenals in good yield and excellent enantioselectivity.

Keywords: acetaldehyde; acetaldehyde dimethyl acetal; cascade reaction; multicomponent reaction; organocatalysis.

Grants and funding

Fabio Pesciaioli thanks the Ministero dell'Università e della Ricerca (PON-AIM1842894, CUPE18D19000560001) for funding this research. Maria Edith Casacchia thanks the support of the Italian national inter-university Ph.D. course in Sustainable Development and Climate Change. Alessio Carioscia acknowledges Dipharma Francis for supporting his Ph.D. fellowship. Alessandro Brusa and Armando Carlone acknowledge funding by the European Union - NextGenerationEU under the Italian Ministry of University and Research (MUR) National Innovation Ecosystem grant ECS00000041 - VITALITY - CUP E13C22001060006. Giuliana Giorgianni thanks the Ministero dell'Università e della Ricerca (PON-DOT13OV2OC) for an industrial Ph.D. fellowship.