Suzuki-Miyaura Cross-Coupling of Bromotryptophan Derivatives at Ambient Temperature.

ABSTRACT: Mild reaction conditions are highly desirable for bio-orthogonal side chain derivatizations of amino acids, peptides or proteins due to the sensitivity of these substrates. Transition metal catalysed cross-couplings such as Suzuki-Miyaura reactions are highly versatile, but usually require unfavourable reaction conditions, in particular, when applied with aryl bromides. Ligand-free solvent-stabilised Pd-nanoparticles represent an efficient and sustainable alternative to conventional phosphine-based catalysts, because the cross-coupling can be performed at considerably lower temperature. We report on the application of such a highly reactive heterogeneous catalyst for the Suzuki-Miyaura cross-coupling of brominated tryptophan derivatives. The solvent-stabilised Pd-nanoparticles are even more efficient than the literature-known ADHP-Pd precatalyst. Interestingly, the latter also leads to the formation of quasi-homogeneous Pd-nanoparticles as the catalytic species. One advantage of our approach is the compatibility with aqueous and aerobic conditions at near-ambient temperatures and short reaction times of only 2?h. The influence of different N^? -protecting groups, boronic acids as well as the impact of different amino acid side chains in bromotryptophan-containing peptides has been studied. Notably, a surprising acceleration of the catalysis was observed when palladium-coordinating side chains were present in proximal positions.

SUBMITTER: Dachwitz S 

PROVIDER: S-EPMC7756874 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature