Visible-Light-Induced Radical gem-Iodoallylation of 2,2,2-Trifluorodiazoethane

Abstract

A visible-light-induced radical gem-iodoallylation of CF3CHN2 was developed under mild conditions, delivering a variety of α-CF3-substituted homoallylic iodide compounds in moderate to excellent yields. The transformation features broad substrate scope, good functional group compatibility, and operational simplicity. The described protocol provides a convenient and attractive tool to apply CF3CHN2 as CF3-introduction reagent in radical synthetic chemistry.

Catalytic C(sp2)−H Trifluoroethylation of Indoles via Iron‐Carbene Insertion

“…It was not until 2010 that Morandi and Carreira developed a protocol for in‐situ generation of CF 3 CHN 2 in the reaction medium, which becomes popular among different research groups [5] . Recently, CF 3 CHN 2 has become a popular diazo reagent for a series of transformations, such as cycloaddition reaction, [6–9] cyclopropanation reaction, [10–15] X−H insertion reaction, [16–20] Witting type reaction, [21] and Doyle‐Kirmse [22–24] reaction, etc [25–27] . However, on the other hand, C−H bond activation could be an attractive way to incorporate fluoroalkyl groups into drug candidates.…”

“…[5] Recently, CF 3 CHN 2 has become a popular diazo reagent for a series of transformations, such as cycloaddition reaction, [6][7][8][9] cyclopropanation reaction, [10][11][12][13][14][15] XÀ H insertion reaction, [16][17][18][19][20] Witting type reaction, [21] and Doyle-Kirmse [22][23][24] reaction, etc. [25][26][27] However, on the other hand, CÀ H bond activation could be an attractive way to incorporate fluoroalkyl groups into drug candidates. Nevertheless, despite the great progress made in transition metal-catalyzed CÀ H activation (Figure 1a), [28][29][30][31][32][33][34][35] there are still a few notable techniques available for this specific kind of transformation.…”

Copper-catalyzed multicomponent reaction of β-trifluoromethyl β-diazo esters enabling the synthesis of β-trifluoromethyl N,N-diacyl-β-amino esters

“…Fluoroalkyldiazo compounds belong to the most versatile and valuable reagents in organic synthesis, as they can be used as diazo intermediates or carbene precursors for the rapid construction of complex molecules along with the introduction of fluoroalkyl groups [14][15][16]. Although the reaction of trifluorodiazoethane [17][18][19][20][21][22][23][24][25][26][27] as well as α-diazo esters [28][29][30] have been widely explored, β-trifluoromethyl β-diazo esters have been less investigated, mainly due to the instability of such structures. Therefore, methods for the synthesis of β-trifluoromethyl β-diazo esters and their applications in organic synthesis are needed but remain challenging.…”

Visible Light-Driven α-Diazoketones as Denitrogenated Synthons: Synthesis of Fluorinated N-Heterocycles via Multicomponent Cyclization Reactions

“…6 For example, in 2023, Wu and co-workers have reported a visible light-induced process for the synthesis of α-CF 3 -substituted linear organofluorides. 7 Notably, this work used CF 3 CHN 2 as a fluorine reagent, which achieved not only the introduction of a CF 3 group but also the generation of radical species (Scheme 1a). However, the introduction of a CF 3 group into diazocarbonyl compounds with similar stability but a wider range of substrates than CF 3 CHN 2 is still mainly stuck in the carbene process.…”

“…In contrast, there has been little progress in visible light-driven diazo compounds as precursors of radicals until recently . For example, in 2023, Wu and co-workers have reported a visible light-induced process for the synthesis of α-CF 3 -substituted linear organofluorides . Notably, this work used CF 3 CHN 2 as a fluorine reagent, which achieved not only the introduction of a CF 3 group but also the generation of radical species (Scheme a).…”