Facile Access to Hindered Ethers via Photoinduced O–H Bond Insertions

The synthesis of the hindered and polyfluorinated dialkyl ethers poses challenges owing to the bulkiness of tertiary alcohols and the low nucleophilicity of polyfluorinated alcohols. Additionally, associated competitive side reactions always provide poor reactivities. Although certain strategies, such as electrocatalytic decarboxylation and hydroalkoxylation, have been explored, a straightforward method for obtaining ethers with structural diversity remains elusive. In this study, we have exploited the photoinduced approach that involves the <i>in situ</i> formation of singlet carbenes followed by O-H insertions to access the hindered and polyfluorinated ethers with congested or polyfluorinated alcohols. Moreover, other nucleophiles such as phenols, H₂O, thiols, silanols, tributyltin hydride, <i>etc</i>., are also tolerable to obtain valuable products. The gram-scale synthesis of marketed drugs and the modification of complex molecules demonstrate the practicality of this approach. The detailed mechanistic studies have elucidated the key intermediates and reaction mechanism, which were distinct from traditional metal-carbenoid O-H insertions.