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 photochemicalmethod 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 TCarbFazetidines 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.
Photochemical thiocarbonyl difluoride generation enables azetidine synthesis
Federico Droghetti;Mirco Natali;
2026
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 photochemicalmethod 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 TCarbFazetidines 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.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
