Difluoroacetaldehyde N-Triftosylhydrazone (DFHZ-Tfs) as a Bench-Stable Crystalline Diazo Surrogate for Diazoacetaldehyde and Difluorodiazoethane

Abstract

Despite the growing importance of volatile functionalized diazoalkanes in organic synthesis, their safe generation and utilization remain a formidable challenge because of their difficult handling along with storage and security issues. In this study, we developed a bench-stable difluoroacetaldehyde N-triftosylhydrazone (DFHZ-Tfs) as an operationally safe diazo surrogate that can release in situ two low-molecular-weight diazoalkanes, diazoacetaldehyde (CHOCHN₂ ) or difluorodiazoethane (CF₂ HCHN₂ ), in a controlled fashion under specific conditions. DFHZ-Tfs has been successfully employed in the Fe-catalyzed cyclopropanation and Doyle-Kirmse reactions, thus highlighting the synthetic utility of DFHZ-Tfs in the efficient construction of molecule frameworks containing CHO or CF₂ H groups. Moreover, the reaction mechanism for the generation of CHOCHN₂ from CF₂ HCHN₂ was elucidated by density functional theory (DFT) calculations.

Keywords: Doyle-Kirmse reaction; cyclopropanation; density functional calculations; diazo compounds; difluoroacetaldehyde N-triftosylhydrazone.