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Exporting Metal‐Carbene Chemistry to Live Mammalian Cells: Copper‐Catalyzed Intracellular Synthesis of Quinoxalines Enabled by N−H Carbene Insertions
Author(s) -
Gutiérrez Sara,
TomásGamasa María,
Mascareñas José L.
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202108899
Subject(s) - carbene , copper , catalysis , chemistry , intracellular , metal , combinatorial chemistry , organic chemistry , biochemistry
Implementing catalytic organometallic transformations in living settings can offer unprecedented opportunities in chemical biology and medicine. Unfortunately, the number of biocompatible reactions so far discovered is very limited, and essentially restricted to uncaging processes. Here, we demonstrate the viability of performing metal carbene transfer reactions in live mammalian cells. In particular, we show that copper (II) catalysts can promote the intracellular annulation of alpha‐keto diazocarbenes with ortho‐amino arylamines, in a process that is initiated by an N‐H carbene insertion. The potential of this transformation is underscored by the in cellulo synthesis of a product that alters mitochondrial functions, and by demonstrating cell selective biological responses using targeted copper catalysts. Considering the wide reactivity spectrum of metal carbenes, this work opens the door to significantly expanding the repertoire of life‐compatible abiotic reactions.