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Radical hydroxymethylation of alkyl iodides using formaldehyde as a C1 synthon |
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| Authors: | Lewis Caiger Conar Sinton Timothe Constantin James J Douglas Nadeem S Sheikh Fabio Juli Daniele Leonori |
| Institution: | Department of Chemistry, University of Manchester, Manchester M13 9PL UK.; Early Chemical Development, Pharmaceuticals Sciences, R&D, AstraZeneca, Macclesfield, UK ; Department of Chemistry, College of Science, King Faisal University, P. O. Box 400, Al-Ahsa 31982 Saudi Arabia |
| Abstract: | 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 PPh3. This event delivers a phosphoranyl radical that re-generates the alkyl radical and provides the hydroxymethylated product.Halogen-atom transfer (XAT) based on phosphoranyl radical chemistry enables the hydroxymethylation of alkyl iodides with formaldehyde. |
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