Site-Selective Functionalization of (sp3)C-H Bonds Catalyzed by Artificial Metalloenzymes Containing an Iridium-Porphyrin Cofactor
Abstract
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.
- Authors:
-
- Univ. of California, Berkeley, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES)
- OSTI Identifier:
- 1633240
- Alternate Identifier(s):
- OSTI ID: 1558124
- Grant/Contract Number:
- AC02-05CH11231
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Angewandte Chemie (International Edition)
- Additional Journal Information:
- Journal Name: Angewandte Chemie (International Edition); Journal Volume: 58; Journal Issue: 39; Journal ID: ISSN 1433-7851
- Publisher:
- Wiley
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
Citation Formats
Gu, Yang, Natoli, Sean N., Liu, Zhennan, Clark, Douglas S., and Hartwig, John F. Site-Selective Functionalization of (sp3)C-H Bonds Catalyzed by Artificial Metalloenzymes Containing an Iridium-Porphyrin Cofactor. United States: N. p., 2019.
Web. doi:10.1002/anie.201907460.
Gu, Yang, Natoli, Sean N., Liu, Zhennan, Clark, Douglas S., & Hartwig, John F. Site-Selective Functionalization of (sp3)C-H Bonds Catalyzed by Artificial Metalloenzymes Containing an Iridium-Porphyrin Cofactor. United States. https://doi.org/10.1002/anie.201907460
Gu, Yang, Natoli, Sean N., Liu, Zhennan, Clark, Douglas S., and Hartwig, John F. Mon .
"Site-Selective Functionalization of (sp3)C-H Bonds Catalyzed by Artificial Metalloenzymes Containing an Iridium-Porphyrin Cofactor". United States. https://doi.org/10.1002/anie.201907460. https://www.osti.gov/servlets/purl/1633240.
@article{osti_1633240,
title = {Site-Selective Functionalization of (sp3)C-H Bonds Catalyzed by Artificial Metalloenzymes Containing an Iridium-Porphyrin Cofactor},
author = {Gu, Yang and Natoli, Sean N. and Liu, Zhennan and Clark, Douglas S. and Hartwig, John F.},
abstractNote = {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.},
doi = {10.1002/anie.201907460},
journal = {Angewandte Chemie (International Edition)},
number = 39,
volume = 58,
place = {United States},
year = {Mon Sep 23 00:00:00 EDT 2019},
month = {Mon Sep 23 00:00:00 EDT 2019}
}
Web of Science
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