Transition Metal-Free N-S Bond Cleavage and C-N Bond Activation of Ugi-Adducts for Rapid Preparation of Primary Amides and α-Ketoamides

Chao Liu; Johan Van der Eycken; Erik V Van der Eycken

doi:10.1002/chem.202301541

Transition Metal-Free N-S Bond Cleavage and C-N Bond Activation of Ugi-Adducts for Rapid Preparation of Primary Amides and α-Ketoamides

Chemistry. 2023 Sep 21;29(53):e202301541. doi: 10.1002/chem.202301541. Epub 2023 Aug 21.

Authors

Chao Liu¹, Johan Van der Eycken², Erik V Van der Eycken^{1

3}

Affiliations

¹ Laboratory for Organic & Microwave-Assisted Chemistry (LOMAC), Department of Chemistry, University of Leuven (KU Leuven), Celestijnenlaan 200F, 3001, Leuven, Belgium.
² Laboratory for Organic and Bio-Organic Synthesis, Department of Organic and Macromolecular Chemistry, Ghent University, Krijgslaan 281 (S.4), Ghent, 9000, Belgium.
³ Peoples' Friendship University of Russia (RUDN University), Miklukho-Maklaya street 6, Moskva, RU-117198, Moscow, Russia.

PMID: 37410246
DOI: 10.1002/chem.202301541

Abstract

A novel method of transition metal-free N-S bond cleavage and subsequent C-N bond activation of Ugi-adducts was developed. Diverse primary amides and α-ketoamides were prepared in a rapid, step-economical and highly efficient manner in two steps. This strategy features excellent chemoselectivity, high yield and functional-group tolerance. Primary amides derived from the pharmaceuticals probenecid and febuxostat were prepared. This method opens a new pathway for the simultaneous synthesis of primary amides and α-ketoamides in an environmentally friendly manner.

Keywords: C−N bond activation; N−S bond cleavage; Ugi reaction; amides; α-ketoamides.