Photochemical thiocarbonyl difluoride generation enables azetidine synthesis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41673007.
- Also identified by DOI 10.1038/s41467-026-69464-3 and PMC identifier 13004840.
- Licence recorded as CC BY-NC-ND.
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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.