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Site‐Selective Functionalization of (sp 3 )C−H Bonds Catalyzed by Artificial Metalloenzymes Containing an Iridium‐Porphyrin Cofactor
Author(s) -
Gu Yang,
Natoli Sean N.,
Liu Zhennan,
Clark Douglas S.,
Hartwig John F.
Publication year - 2019
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.201907460
Subject(s) - porphyrin , iridium , chemistry , catalysis , steric effects , combinatorial chemistry , molecule , selectivity , surface modification , stereochemistry , cofactor , photochemistry , organic chemistry , enzyme
The selective functionalization of one C−H bond over others in nearly identical steric and electronic environments can facilitate the construction of complex molecules. We report site‐selective functionalizations of C−H bonds, differentiated solely by remote substituents, catalyzed by artificial metalloenzymes (ArMs) that are generated from the combination of an evolvable P450 scaffold and an iridium‐porphyrin cofactor. The generated systems catalyze the insertion of carbenes into the C−H bonds of a range of phthalan derivatives containing substituents that render the two methylene positions in each phthalan inequivalent. These reactions occur with site‐selectivity ratios of up to 17.8:1 and, in most cases, with pairs of enzyme mutants that preferentially form each of the two constitutional isomers. This study demonstrates the potential of abiotic reactions catalyzed by metalloenzymes to functionalize C−H bonds with site selectivity that is difficult to achieve with small‐molecule catalysts.