Dominik K. Kölmel; Jiang Meng; Mei-Hsuan Tsai; Jiamin Que; Richard P. Loach; Thomas Knauber; Jinqiao Wan; Mark E. Flanagan
ACS Comb. Sci., 2019, 21, 8, 588-597
https://doi.org/10.1021/acscombsci.9b00076

Abstract

A new catalytic manifold that merges photoredox with nickel catalysis in aqueous solution is presented. Specifically, the combination of a highly active, yet air-stable, nickel pre-catalyst with a new electron-deficient pyridyl carboxamidine ligand was key to the development of a water-compatible nickel catalysis platform, which is a crucial requirement for the preparation of DNA-encoded libraries (DELs). Together with an iridium-based photocatalyst and a powerful light source, this dual catalysis approach enabled the efficient decarboxylative arylation of α-amino acids with DNA-tagged aryl halides. This C(sp2)-C(sp3) coupling tolerates a wide variety of functional groups on both the amino acid and the aryl halide substrates. Due to the mild and DNA-compatible reaction conditions, the presented transformation holds great potential for the construction of DELs. This was further evidenced by showing that well plate-compatible LED arrays can serve as competent light sources to facilitate parallel synthesis. Lastly, we demonstrate that this procedure can serve as a blueprint toward the adaptation of other established nickel metallaphotoredox transformations to the idiosyncratic requirements of DEL.