Enantioselective Csp3-Csp3 formation by nickel-catalyzed enantioconvergent cross-electrophile alkyl-alkyl coupling of unactivated alkyl halides

The pervasive occurrence of saturated stereogenic carbon centers in pharmaceuticals, agrochemicals, functional organic materials, and natural products has stimulated great efforts toward the construction of such saturated carbon centers. We report a reaction mode for the enantioselective constructio...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhao, Wen-Tao, Shu, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10328415/
https://www.ncbi.nlm.nih.gov/pubmed/37418514
http://dx.doi.org/10.1126/sciadv.adg9898
_version_ 1785069794780774400
author Zhao, Wen-Tao
Shu, Wei
author_facet Zhao, Wen-Tao
Shu, Wei
author_sort Zhao, Wen-Tao
collection PubMed
description The pervasive occurrence of saturated stereogenic carbon centers in pharmaceuticals, agrochemicals, functional organic materials, and natural products has stimulated great efforts toward the construction of such saturated carbon centers. We report a reaction mode for the enantioselective construction of alkyl-alkyl bond to access saturated stereogenic carbon centers by asymmetric reductive cross-coupling between different alkyl electrophiles in good yields with great levels of enantioselectivity. This reaction mode uses only alkyl electrophiles for enantioselective C(sp3)-C(sp3) bond-formation, rendering reductive alkyl-alkyl cross-coupling as an alternative to traditional alkyl-alkyl cross-coupling reactions between alkyl nucleophiles and alkyl electrophiles to access saturated stereogenic carbon centers without the use of organometallic reagents. The reaction displays a broad scope for two alkyl electrophiles with good functional group tolerance. Mechanistic studies reveal that the reaction undergoes a single electron transfer that enabled the reductive coupling pathway to form the alkyl-alkyl bond.
format Online
Article
Text
id pubmed-10328415
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher American Association for the Advancement of Science
record_format MEDLINE/PubMed
spelling pubmed-103284152023-07-08 Enantioselective Csp3-Csp3 formation by nickel-catalyzed enantioconvergent cross-electrophile alkyl-alkyl coupling of unactivated alkyl halides Zhao, Wen-Tao Shu, Wei Sci Adv Physical and Materials Sciences The pervasive occurrence of saturated stereogenic carbon centers in pharmaceuticals, agrochemicals, functional organic materials, and natural products has stimulated great efforts toward the construction of such saturated carbon centers. We report a reaction mode for the enantioselective construction of alkyl-alkyl bond to access saturated stereogenic carbon centers by asymmetric reductive cross-coupling between different alkyl electrophiles in good yields with great levels of enantioselectivity. This reaction mode uses only alkyl electrophiles for enantioselective C(sp3)-C(sp3) bond-formation, rendering reductive alkyl-alkyl cross-coupling as an alternative to traditional alkyl-alkyl cross-coupling reactions between alkyl nucleophiles and alkyl electrophiles to access saturated stereogenic carbon centers without the use of organometallic reagents. The reaction displays a broad scope for two alkyl electrophiles with good functional group tolerance. Mechanistic studies reveal that the reaction undergoes a single electron transfer that enabled the reductive coupling pathway to form the alkyl-alkyl bond. American Association for the Advancement of Science 2023-07-07 /pmc/articles/PMC10328415/ /pubmed/37418514 http://dx.doi.org/10.1126/sciadv.adg9898 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Physical and Materials Sciences
Zhao, Wen-Tao
Shu, Wei
Enantioselective Csp3-Csp3 formation by nickel-catalyzed enantioconvergent cross-electrophile alkyl-alkyl coupling of unactivated alkyl halides
title Enantioselective Csp3-Csp3 formation by nickel-catalyzed enantioconvergent cross-electrophile alkyl-alkyl coupling of unactivated alkyl halides
title_full Enantioselective Csp3-Csp3 formation by nickel-catalyzed enantioconvergent cross-electrophile alkyl-alkyl coupling of unactivated alkyl halides
title_fullStr Enantioselective Csp3-Csp3 formation by nickel-catalyzed enantioconvergent cross-electrophile alkyl-alkyl coupling of unactivated alkyl halides
title_full_unstemmed Enantioselective Csp3-Csp3 formation by nickel-catalyzed enantioconvergent cross-electrophile alkyl-alkyl coupling of unactivated alkyl halides
title_short Enantioselective Csp3-Csp3 formation by nickel-catalyzed enantioconvergent cross-electrophile alkyl-alkyl coupling of unactivated alkyl halides
title_sort enantioselective csp3-csp3 formation by nickel-catalyzed enantioconvergent cross-electrophile alkyl-alkyl coupling of unactivated alkyl halides
topic Physical and Materials Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10328415/
https://www.ncbi.nlm.nih.gov/pubmed/37418514
http://dx.doi.org/10.1126/sciadv.adg9898
work_keys_str_mv AT zhaowentao enantioselectivecsp3csp3formationbynickelcatalyzedenantioconvergentcrosselectrophilealkylalkylcouplingofunactivatedalkylhalides
AT shuwei enantioselectivecsp3csp3formationbynickelcatalyzedenantioconvergentcrosselectrophilealkylalkylcouplingofunactivatedalkylhalides