Photochemical thiocarbonyl difluoride generation enables azetidine synthesis

光化学硫代羰基二氟化物生成可用于氮杂环丁烷的合成。

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Abstract

The activation of amines into thiocarbamoyl fluorides (TCarbFs) provides access to valuable nitrogen-based functionalities. However, their broader use has been hindered by the reliance on harsh reagents and conditions. Here we report a photochemical method for in situ generation of thiocarbonyl difluoride (TCF) from N-trifluoromethylthiophthalimide (Phth-SCF₃) using visible light and organic reductants. This strategy allows the synthesis of structurally complex azetidines from strained azabicyclo[1.1.0]butanes (ABBs). TCF-mediated ring opening followed by semipinacol rearrangement or nucleophilic additions enables direct access to spiro- and fluorinated TCarbF-azetidines in a single step. Mechanistic studies support a single-electron reduction pathway and rationalize the impact of the photocatalyst on the observed selectivity. The discovery offers a general platform for amine activation and addresses a long-standing gap in azetidine functionalization.

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