Photochemical thiocarbonyl difluoride generation enables azetidine synthesis
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. The activation of amines into thiocarbamoyl fluorides provides access to valuable nitrogen-based functionalities. Here, the authors report a mild, photochemical method for in-situ generation of thiocarbonyl difluoride from N-trifluoromethylthiophthalimide using visible light and organic reductants, and apply this strategy to the synthesis of azetidines from strained azabicyclo[1.1.0]butanes.
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BibTeX
@article{rodriguez2026photochemical,
title = {{Photochemical thiocarbonyl difluoride generation enables azetidine synthesis}},
author = {Ricardo I. Rodríguez and Julien Paut and Giona Armellin and Stefano Visentini and Gabriel Cormier and Federico Droghetti and Mirco Natali and Marco Bortolus and Giorgio Pelosi and Luca Dell' Amico},
journal = {Nature Communications},
year = {2026},
month = nov,
doi = {10.1038/s41467-026-69464-3},
url = {https://hal.science/hal-05651940v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Photochemical thiocarbonyl difluoride generation enables azetidine synthesis
AU - Ricardo I. Rodríguez
AU - Julien Paut
AU - Giona Armellin
AU - Stefano Visentini
AU - Gabriel Cormier
AU - Federico Droghetti
AU - Mirco Natali
AU - Marco Bortolus
AU - Giorgio Pelosi
AU - Luca Dell' Amico
PY - 2026
DA - 2026/11/03
JO - Nature Communications
DO - 10.1038/s41467-026-69464-3
UR - https://hal.science/hal-05651940v1
AB - 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. The activation of amines into thiocarbamoyl fluorides provides access to valuable nitrogen-based functionalities. Here, the authors report a mild, photochemical method for in-situ generation of thiocarbonyl difluoride from N-trifluoromethylthiophthalimide using visible light and organic reductants, and apply this strategy to the synthesis of azetidines from strained azabicyclo[1.1.0]butanes.
SN - 2041-1723
SN - 2041-1723
ER -