Visible‐Light‐Mediated Selective Arylation of Cysteine in Batch and Flow

Abstract

A mild visible‐light‐mediated strategy for cysteine arylation is presented. The method relies on the use of eosin Y as a metal‐free photocatalyst and aryldiazonium salts as arylating agents. The reaction can be significantly accelerated in a microflow reactor, whilst allowing the in situ formation of the required diazonium salts. The batch and flow protocol described herein can be applied to obtain a broad series of arylated cysteine derivatives and arylated cysteine‐containing dipeptides. Moreover, the method was applied to the chemoselective arylation of a model peptide in biocompatible reaction conditions (room temperature, phosphate‐buffered saline (PBS) buffer) within a short reaction time.

Photocatalytic Modification of Amino Acids, Peptides, and Proteins

“…Nola nd co-workers developed ap hotocatalytic arylation protocolb ased on the classical Stadler-Ziegler reaction. [21] The protocol involves the use of aryldiazonium salts (E red as high as 0.5 Vv ersus as tandard calomel electrode (SCE)), which generate aryl radicals in the presence of Eosin Yast he photocatalyst (Scheme6). These electrophilica ryl radicals can be easily trappedb yc ysteine, resulting in the formation of ac ovalent CÀSb ond.…”

Japan Prize: A. Yoshino / Merck–Banyu Lectureship: N. Kumagai / DECHEMA Prize: T. Noël

“…Noël and his group are interested in the development of new catalytic strategies and technologies for chemical synthesis, and he was honored for his work on continuous photochemical conversion in microfluidic systems. He has reported in Angewandte Chemie on the visible‐light‐mediated arylation of cysteine in batch and flow, and on selective C(sp 3 )−H aerobic oxidation enabled by photocatalysis in flow …”

Visible‐Light‐Mediated S−H Bond Insertion Reactions of Diazoalkanes with Cysteine Residues in Batch and Flow

“…[11] For example, Noël and co-workers reported a protocol involving visible-light-mediated arylation of cysteine and using corresponding diazonium salts as the aryl source (Scheme 1A). [12] The Molander group developed a method involving a Ni/photoredox catalysis of thioarylation of cysteine-containing peptides (Scheme 1B). [13] Despite these significant achievements, the development of general methods for selective cysteine modification under mild conditions with readily available reagents is still highly desirable.…”