Cargando…
Radical Redox Annulations: A General Light-Driven Method for the Synthesis of Saturated Heterocycles
[Image: see text] We introduce here a two-component annulation strategy that provides access to a diverse collection of five- and six-membered saturated heterocycles from aryl alkenes and a family of redox-active radical precursors bearing tethered nucleophiles. This transformation is mediated by a...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2022
|
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9638994/ https://www.ncbi.nlm.nih.gov/pubmed/36366762 http://dx.doi.org/10.1021/acscatal.2c04316 |
_version_ | 1784825543378599936 |
---|---|
author | Murray, Philip R. D. Leibler, Isabelle Nathalie-Marie Hell, Sandrine M. Villalona, Eris Doyle, Abigail G. Knowles, Robert R. |
author_facet | Murray, Philip R. D. Leibler, Isabelle Nathalie-Marie Hell, Sandrine M. Villalona, Eris Doyle, Abigail G. Knowles, Robert R. |
author_sort | Murray, Philip R. D. |
collection | PubMed |
description | [Image: see text] We introduce here a two-component annulation strategy that provides access to a diverse collection of five- and six-membered saturated heterocycles from aryl alkenes and a family of redox-active radical precursors bearing tethered nucleophiles. This transformation is mediated by a combination of an Ir(III) photocatalyst and a Brønsted acid under visible-light irradiation. A reductive proton-coupled electron transfer generates a reactive radical which undergoes addition to an alkene. Then, an oxidative radical-polar crossover step leading to carbocation formation is followed by ring closure through cyclization of the tethered nucleophile. A wide range of heterocycles are easily accessible, including pyrrolidines, piperidines, tetrahydrofurans, morpholines, δ-valerolactones, and dioxanones. We demonstrate the scope of this approach through broad structural variation of both reaction components. This method is amenable to gram-scale preparation and to complex fragment coupling. |
format | Online Article Text |
id | pubmed-9638994 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-96389942022-11-08 Radical Redox Annulations: A General Light-Driven Method for the Synthesis of Saturated Heterocycles Murray, Philip R. D. Leibler, Isabelle Nathalie-Marie Hell, Sandrine M. Villalona, Eris Doyle, Abigail G. Knowles, Robert R. ACS Catal [Image: see text] We introduce here a two-component annulation strategy that provides access to a diverse collection of five- and six-membered saturated heterocycles from aryl alkenes and a family of redox-active radical precursors bearing tethered nucleophiles. This transformation is mediated by a combination of an Ir(III) photocatalyst and a Brønsted acid under visible-light irradiation. A reductive proton-coupled electron transfer generates a reactive radical which undergoes addition to an alkene. Then, an oxidative radical-polar crossover step leading to carbocation formation is followed by ring closure through cyclization of the tethered nucleophile. A wide range of heterocycles are easily accessible, including pyrrolidines, piperidines, tetrahydrofurans, morpholines, δ-valerolactones, and dioxanones. We demonstrate the scope of this approach through broad structural variation of both reaction components. This method is amenable to gram-scale preparation and to complex fragment coupling. American Chemical Society 2022-10-26 2022-11-04 /pmc/articles/PMC9638994/ /pubmed/36366762 http://dx.doi.org/10.1021/acscatal.2c04316 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Murray, Philip R. D. Leibler, Isabelle Nathalie-Marie Hell, Sandrine M. Villalona, Eris Doyle, Abigail G. Knowles, Robert R. Radical Redox Annulations: A General Light-Driven Method for the Synthesis of Saturated Heterocycles |
title | Radical Redox Annulations:
A General Light-Driven
Method for the Synthesis of Saturated Heterocycles |
title_full | Radical Redox Annulations:
A General Light-Driven
Method for the Synthesis of Saturated Heterocycles |
title_fullStr | Radical Redox Annulations:
A General Light-Driven
Method for the Synthesis of Saturated Heterocycles |
title_full_unstemmed | Radical Redox Annulations:
A General Light-Driven
Method for the Synthesis of Saturated Heterocycles |
title_short | Radical Redox Annulations:
A General Light-Driven
Method for the Synthesis of Saturated Heterocycles |
title_sort | radical redox annulations:
a general light-driven
method for the synthesis of saturated heterocycles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9638994/ https://www.ncbi.nlm.nih.gov/pubmed/36366762 http://dx.doi.org/10.1021/acscatal.2c04316 |
work_keys_str_mv | AT murrayphiliprd radicalredoxannulationsagenerallightdrivenmethodforthesynthesisofsaturatedheterocycles AT leiblerisabellenathaliemarie radicalredoxannulationsagenerallightdrivenmethodforthesynthesisofsaturatedheterocycles AT hellsandrinem radicalredoxannulationsagenerallightdrivenmethodforthesynthesisofsaturatedheterocycles AT villalonaeris radicalredoxannulationsagenerallightdrivenmethodforthesynthesisofsaturatedheterocycles AT doyleabigailg radicalredoxannulationsagenerallightdrivenmethodforthesynthesisofsaturatedheterocycles AT knowlesrobertr radicalredoxannulationsagenerallightdrivenmethodforthesynthesisofsaturatedheterocycles |