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Suzuki–Miyaura Cross‐Coupling of Bromotryptophan Derivatives at Ambient Temperature
Author(s) -
Dachwitz Steffen,
Duwe Dario H.,
Wang Yating Hong,
Gruß Hendrik,
Hannappel Yvonne,
Hellweg Thomas,
Sewald Norbert
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202002454
Subject(s) - chemistry , catalysis , side chain , boronic acid , palladium , combinatorial chemistry , nanoparticle , aryl , amino acid , coupling reaction , solvent , aqueous solution , ligand (biochemistry) , phosphine , homogeneous , tryptophan , organic chemistry , nanotechnology , materials science , alkyl , polymer , biochemistry , receptor , physics , thermodynamics
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 α ‐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.