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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...

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Autores principales: Nakafuku, Kohki M., Zhang, Zuxiao, Wappes, Ethan A., Stateman, Leah M., Chen, Andrew D., Nagib, David A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
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.
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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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