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Enantioselective radical C–H amination for the synthesis of β-amino alcohols
Asymmetric, radical C–H functionalizations are rare, yet powerful tools for solving modern synthetic challenges. Specifically, the enantio- and regio-selective C–H amination of alcohols to access medicinally valuable, chiral β-amino alcohols remains elusive. To solve this challenge, a radical relay...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390680/ https://www.ncbi.nlm.nih.gov/pubmed/32572164 http://dx.doi.org/10.1038/s41557-020-0482-8 |
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author | Nakafuku, Kohki M. Zhang, Zuxiao Wappes, Ethan A. Stateman, Leah M. Chen, Andrew D. Nagib, David A. |
author_facet | Nakafuku, Kohki M. Zhang, Zuxiao Wappes, Ethan A. Stateman, Leah M. Chen, Andrew D. Nagib, David A. |
author_sort | Nakafuku, Kohki M. |
collection | PubMed |
description | Asymmetric, radical C–H functionalizations are rare, yet powerful tools for solving modern synthetic challenges. Specifically, the enantio- and regio-selective C–H amination of alcohols to access medicinally valuable, chiral β-amino alcohols remains elusive. To solve this challenge, a radical relay chaperone strategy was designed, wherein an alcohol is transiently converted to an imidate radical that undergoes intramolecular H-atom transfer (HAT). This regioselective HAT was also rendered enantioselective by harnessing energy transfer catalysis to mediate selective radical generation and interception by a chiral copper catalyst. The successful development of this multi-catalytic, asymmetric, radical C–H amination enables broad access to chiral β-amino alcohols from a variety of alcohols containing alkyl, allyl, benzyl, and propargyl C–H bonds. Mechanistic experiments reveal triplet energy sensitization of a Cu-bound radical precursor facilitates catalyst-mediated HAT stereoselectivity – enabling the synthesis of several important classes of chiral β-amines by enantioselective, radical C–H amination. |
format | Online Article Text |
id | pubmed-7390680 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
record_format | MEDLINE/PubMed |
spelling | pubmed-73906802020-12-22 Enantioselective radical C–H amination for the synthesis of β-amino alcohols Nakafuku, Kohki M. Zhang, Zuxiao Wappes, Ethan A. Stateman, Leah M. Chen, Andrew D. Nagib, David A. Nat Chem Article Asymmetric, radical C–H functionalizations are rare, yet powerful tools for solving modern synthetic challenges. Specifically, the enantio- and regio-selective C–H amination of alcohols to access medicinally valuable, chiral β-amino alcohols remains elusive. To solve this challenge, a radical relay chaperone strategy was designed, wherein an alcohol is transiently converted to an imidate radical that undergoes intramolecular H-atom transfer (HAT). This regioselective HAT was also rendered enantioselective by harnessing energy transfer catalysis to mediate selective radical generation and interception by a chiral copper catalyst. The successful development of this multi-catalytic, asymmetric, radical C–H amination enables broad access to chiral β-amino alcohols from a variety of alcohols containing alkyl, allyl, benzyl, and propargyl C–H bonds. Mechanistic experiments reveal triplet energy sensitization of a Cu-bound radical precursor facilitates catalyst-mediated HAT stereoselectivity – enabling the synthesis of several important classes of chiral β-amines by enantioselective, radical C–H amination. 2020-06-22 2020-08 /pmc/articles/PMC7390680/ /pubmed/32572164 http://dx.doi.org/10.1038/s41557-020-0482-8 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Nakafuku, Kohki M. Zhang, Zuxiao Wappes, Ethan A. Stateman, Leah M. Chen, Andrew D. Nagib, David A. Enantioselective radical C–H amination for the synthesis of β-amino alcohols |
title | Enantioselective radical C–H amination for the synthesis of β-amino alcohols |
title_full | Enantioselective radical C–H amination for the synthesis of β-amino alcohols |
title_fullStr | Enantioselective radical C–H amination for the synthesis of β-amino alcohols |
title_full_unstemmed | Enantioselective radical C–H amination for the synthesis of β-amino alcohols |
title_short | Enantioselective radical C–H amination for the synthesis of β-amino alcohols |
title_sort | enantioselective radical c–h amination for the synthesis of β-amino alcohols |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390680/ https://www.ncbi.nlm.nih.gov/pubmed/32572164 http://dx.doi.org/10.1038/s41557-020-0482-8 |
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