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Radical hydroxymethylation of alkyl iodides using formaldehyde as a C1 synthon
Radical hydroxymethylation using formaldehyde as a C1 synthon is challenging due to the reversible and endothermic nature of the addition process. Here we report a strategy that couples alkyl iodide building blocks with formaldehyde through the use of photocatalysis and a phosphine additive. Halogen...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8356745/ https://www.ncbi.nlm.nih.gov/pubmed/34447537 http://dx.doi.org/10.1039/d1sc03083c |
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author | Caiger, Lewis Sinton, Conar Constantin, Timothée Douglas, James J. Sheikh, Nadeem S. Juliá, Fabio Leonori, Daniele |
author_facet | Caiger, Lewis Sinton, Conar Constantin, Timothée Douglas, James J. Sheikh, Nadeem S. Juliá, Fabio Leonori, Daniele |
author_sort | Caiger, Lewis |
collection | PubMed |
description | Radical hydroxymethylation using formaldehyde as a C1 synthon is challenging due to the reversible and endothermic nature of the addition process. Here we report a strategy that couples alkyl iodide building blocks with formaldehyde through the use of photocatalysis and a phosphine additive. Halogen-atom transfer (XAT) from α-aminoalkyl radicals is leveraged to convert the iodide into the corresponding open-shell species, while its following addition to formaldehyde is rendered irreversible by trapping the transient O-radical with PPh(3). This event delivers a phosphoranyl radical that re-generates the alkyl radical and provides the hydroxymethylated product. |
format | Online Article Text |
id | pubmed-8356745 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-83567452021-08-25 Radical hydroxymethylation of alkyl iodides using formaldehyde as a C1 synthon Caiger, Lewis Sinton, Conar Constantin, Timothée Douglas, James J. Sheikh, Nadeem S. Juliá, Fabio Leonori, Daniele Chem Sci Chemistry Radical hydroxymethylation using formaldehyde as a C1 synthon is challenging due to the reversible and endothermic nature of the addition process. Here we report a strategy that couples alkyl iodide building blocks with formaldehyde through the use of photocatalysis and a phosphine additive. Halogen-atom transfer (XAT) from α-aminoalkyl radicals is leveraged to convert the iodide into the corresponding open-shell species, while its following addition to formaldehyde is rendered irreversible by trapping the transient O-radical with PPh(3). This event delivers a phosphoranyl radical that re-generates the alkyl radical and provides the hydroxymethylated product. The Royal Society of Chemistry 2021-07-06 /pmc/articles/PMC8356745/ /pubmed/34447537 http://dx.doi.org/10.1039/d1sc03083c Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/ |
spellingShingle | Chemistry Caiger, Lewis Sinton, Conar Constantin, Timothée Douglas, James J. Sheikh, Nadeem S. Juliá, Fabio Leonori, Daniele Radical hydroxymethylation of alkyl iodides using formaldehyde as a C1 synthon |
title | Radical hydroxymethylation of alkyl iodides using formaldehyde as a C1 synthon |
title_full | Radical hydroxymethylation of alkyl iodides using formaldehyde as a C1 synthon |
title_fullStr | Radical hydroxymethylation of alkyl iodides using formaldehyde as a C1 synthon |
title_full_unstemmed | Radical hydroxymethylation of alkyl iodides using formaldehyde as a C1 synthon |
title_short | Radical hydroxymethylation of alkyl iodides using formaldehyde as a C1 synthon |
title_sort | radical hydroxymethylation of alkyl iodides using formaldehyde as a c1 synthon |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8356745/ https://www.ncbi.nlm.nih.gov/pubmed/34447537 http://dx.doi.org/10.1039/d1sc03083c |
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