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Iridium-catalyzed asymmetric trans-selective hydrogenation of 1,3-disubstituted isoquinolines

Kim, Alexia N. and Ngamnithiporn, Aurapat and Bartberger, Michael D. and Stoltz, Brian M. (2022) Iridium-catalyzed asymmetric trans-selective hydrogenation of 1,3-disubstituted isoquinolines. Chemical Science, 13 (11). pp. 3227-3232. ISSN 2041-6520. PMCID PMC8926345. doi:10.1039/d1sc06729j. https://resolver.caltech.edu/CaltechAUTHORS:20220302-956596361

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Abstract

The development of the first asymmetric trans-selective hydrogenation of 1,3-disubstituted isoquinolines is reported. Utilizing [Ir(cod)Cl]₂ and a commercially available chiral Josiphos ligand, a variety of differentially substituted isoquinolines are hydrogenated to produce enantioenriched trans-tetrahydroisoquinolines in good yield with high levels of enantioselectivity. Directing group studies demonstrate that the hydroxymethyl functionality at the C1 position is critical for hydrogenation to favor the trans-diastereomer. Preliminary mechanistic studies reveal that non-coordinating chlorinated solvents and halide additives are crucial to enable trans-selectivity.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1039/D1SC06729JDOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8926345/PubMed CentralArticle
ORCID:
AuthorORCID
Kim, Alexia N.0000-0002-4060-8892
Ngamnithiporn, Aurapat0000-0002-5389-8171
Bartberger, Michael D.0000-0002-5167-3139
Stoltz, Brian M.0000-0001-9837-1528
Additional Information:© 2022 The Author(s). Published by the Royal Society of Chemistry. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Submitted 02 Dec 2021. Accepted 16 Feb 2022. First published 18 Feb 2022. All publication charges for this article have been paid for by the Royal Society of Chemistry. We thank the NIH-NIGMS (R01GM127972A) and Caltech for financial support. A. N. thanks the Royal Thai Government Scholarship Program. We thank Dr David VanderVelde for NMR expertise, Dr Scott Virgil for instrumentation, Dr Mona Shahgholi for mass spectroscopy, and Dr Michael Takase and Larry Henling for assistance with X-ray analysis. Author contributions. B. M. S. conceived and directed the project. A. N. K. and A. N. designed, performed, and analyzed the synthetic chemistry experiments. M. D. B. assisted with VCD studies of THIQ 2a. A. N. K., A. N., M. D. B., and B. M. S. prepared the manuscript. Data availability. Data for this work, including optimization tables, general experimental procedures, characterization data for all new compounds and X-ray data are provided in the ESI. There are no conflicts to declare.
Funders:
Funding AgencyGrant Number
NIHR01GM127972A
CaltechUNSPECIFIED
Royal Thai Government Scholarship ProgramUNSPECIFIED
Royal Society of ChemistryUNSPECIFIED
Issue or Number:11
PubMed Central ID:PMC8926345
DOI:10.1039/d1sc06729j
Record Number:CaltechAUTHORS:20220302-956596361
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20220302-956596361
Official Citation:Iridium-catalyzed asymmetric trans-selective hydrogenation of 1,3-disubstituted isoquinolines. Chem. Sci., 2022, 13, 3227-3232; DOI: 10.1039/d1sc06729j
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:113679
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:02 Mar 2022 10:38
Last Modified:12 Apr 2022 23:42

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  • Kim, Alexia N. and Ngamnithiporn, Aurapat and Bartberger, Michael D. and Stoltz, Brian M. Iridium-catalyzed asymmetric trans-selective hydrogenation of 1,3-disubstituted isoquinolines. (deposited 02 Mar 2022 10:38) [Currently Displayed]

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