Site-Selective Functionalization of (sp3)C-H Bonds Catalyzed by Artificial Metalloenzymes Containing an Iridium-Porphyrin Cofactor

Gu, Yang; Natoli, Sean N.; Liu, Zhennan; Clark, Douglas S.; Hartwig, John F.

doi:10.1002/ange.201907460

Site-Selective Functionalization of (sp³)C-H Bonds Catalyzed by Artificial Metalloenzymes Containing an Iridium-Porphyrin Cofactor

Journal Article · Mon Jul 29 00:00:00 EDT 2019 · Angewandte Chemie

DOI:https://doi.org/10.1002/ange.201907460· OSTI ID:1608274

Gu, Yang ^[1]; Natoli, Sean N. ^[1]; Liu, Zhennan ^[1]; Clark, Douglas S. ^[2]; ^[1]

Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Chemical Sciences Division
Univ. of California, Berkeley, CA (United States). Dept. of Chemical and Biomolecular Engineering; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging Division

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.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22), Chemical Sciences, Geosciences & Biosciences Division (SC-22.1)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1608274

Alternate ID(s):: OSTI ID: 1558123

Journal Information:: Angewandte Chemie, Journal Name: Angewandte Chemie Journal Issue: 39 Vol. 131; ISSN 0044-8249

Publisher:: German Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: English

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Site-Selective Functionalization of (sp3)C-H Bonds Catalyzed by Artificial Metalloenzymes Containing an Iridium-Porphyrin Cofactor

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References (50)

Cited By (1)

Figures / Tables (8)

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