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 (CF2HCHN2), 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 CF2H groups. Moreover, the reaction mechanism for the generation of CHOCHN2 from CF2HCHN2 was elucidated by density functional theory (DFT) calculations.

Research Progress on EWG-Substituted N-Arylsulfonylhydrazones as the Diazo Compound Precursor

“…2019 年, 我们课题组 [28] 利用三氟取代乙醛的 N-邻三氟甲基苯磺酰腙 44 作为三氟取代重氮乙烷的前体, 在 Fe(TPP)Cl 催化作用下, 与烯丙基或炔丙基硫醚 160 和 162 发生 Doyle-Kirmse 反应, 以高产率制备了一系列 三氟甲基取代的烯烃或联烯基化合物 161 和 163(图 28a). 之后不久, 毕锡和课题组 [40]…”

Recent Progress in the Application of Difluoromethyl Diazomethane as Fluorine-Containing Building Block

“…该团队 [42] 4)仅通过原位 [19] 和非原 位 [29] 方式制备, 且由于反应过程中迅速生成的大量二 氟甲基重氮甲烷(4)会积聚于反应器中, 该制备方法存 在着一定的安全隐患. 2020 年, 毕锡和团队 [48]…”

The Power of Iron Catalysis in Diazo Chemistry

“…The Bi group then investigated N- [2-(trifluoromethyl)phenylsulfonyl]hydrazones as surrogates for diazoacetaldehyde and difluorodiazoethane for ironcatalyzed Doyle-Kirmse rearrangements. 55 Hemin is a native water-soluble iron porphyrin complex that has also been reported as an efficient catalyst for a [2,3]-sigmatropic rearrangement of diazo esters with allyl sulfides under strictly aqueous conditions. The reaction was reported with yields of up to 99% using 2.5 mol% of hemin in H 2 O at 40 °C.…”