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Radical hydroxymethylation of alkyl iodides using formaldehyde as a C1 synthon.

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.

SUBMITTER: Caiger L

PROVIDER: S-EPMC8356745 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Radical hydroxymethylation of alkyl iodides using formaldehyde as a C1 synthon.

Caiger Lewis L Sinton Conar C Constantin Timothée T Douglas James J JJ Sheikh Nadeem S NS Juliá Fabio F Leonori Daniele D

Chemical science 20210706 31

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 t ...[more]

PMID: 34447537

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