Trifluorodiazoethane: A versatile building block to access trifluoromethylated heterocycles

Abstract

Trifluoromethylated heterocycles have attracted remarkable interest in the last decades. The beneficial physicochemical and biological properties imparted by the incorporation of trifluoromethyl group into heterocycles have been the key factors to the frequent occurrence of trifluoromethyl group in several heterocycles of pharmaceutical and agrochemical relevance. In consequence, the construction of this class of compounds has become a major subject of research in recent years. In this context, 2,2,2-trifluorodiazoethane (CF 3 CHN 2 ) has emerged as an important reagent in the synthesis of trifluoromethylated heterocycles, thanks to the versatility of this reagent in undergoing a multitude of synthetic transformations. CF 3 CHN 2 readily participates in [2 + 1]-, [3 + 2]-, and [3 + 3]-cycloaddition reactions, as a trifluoromethyl-containing dipole, thereby creating new approaches to trifluoromethylated heterocycles. The last decade has witnessed phenomenal growth in this area, and now, several methods are available to access highly functionalized 5-and 6-membered trifluoromethyl-containing heterocycles. In this review, we aim to demonstrate the use of CF 3 CHN 2 in the preparation of different classes of CF 3 -substituted heterocycles, giving emphasis to the past 10 years.

Strategies and Methods for the Synthesis of 2‐Pyrazolines: Recent Developments (2012–2022)

“…Trifluorodiazoethane (CF 3 CHN 2 ) is a well‐studied diazoalkane [43a] that is very useful for incorporating trifluoromethyl groups into heterocyclic molecules [43b] . Its explosive nature and tedious handling limited its universal applications, until 2010.…”

Trifluoromethylated 4,5-Dihydro-1,2,4-triazin-6(1H)-ones via (3+3)-Annulation of Nitrile Imines with α-Amino Esters

“…Several synthetic strategies towards F-containing heterocycles, including cycloadditions and cyclocondensation reactions, functional group interconversions, and catalytic C–H functionalizations, have been developed in recent decades and are nicely summarized elsewhere [ 15 , 16 , 17 , 18 ]. In this context, there is increasing interest in the chemistry of fluoroalkylated 1,3-dipoles, which are recognized as highly useful building blocks for Huisgen (3+2)-cycloaddition reactions [ 19 , 20 , 21 , 22 , 23 , 24 ]. For example, despite some limitations and the difficult handling of 2,2,2-trifluorodiazoethane, this highly reactive intermediate has been extensively explored, not only as 1,3-dipolar reagent, but also as a valuable source of the respective carbene employed in (2+1)-annulation reactions [ 22 , 23 , 24 ].…”

“…In this context, there is increasing interest in the chemistry of fluoroalkylated 1,3-dipoles, which are recognized as highly useful building blocks for Huisgen (3+2)-cycloaddition reactions [ 19 , 20 , 21 , 22 , 23 , 24 ]. For example, despite some limitations and the difficult handling of 2,2,2-trifluorodiazoethane, this highly reactive intermediate has been extensively explored, not only as 1,3-dipolar reagent, but also as a valuable source of the respective carbene employed in (2+1)-annulation reactions [ 22 , 23 , 24 ].…”

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

“…Given the widespread applications of trifluoromethyl (CF 3 )-containing compounds in agrochemicals, pharmaceuticals, and functional materials, the development of efficient and mild synthetic methodologies for their synthesis has become an emerging theme in organic synthesis and remains in high demand . In this context, 2,2,2-trifluorodiazoethane (CF 3 CHN 2 ) has attracted considerable attention and emerged as a valuable and versatile fluoroalkylating reagent in the rapid assembly of CF 3 -containing compounds during the past decade . It has been extensively used as a metal–carbene precursor of transition-metal catalysts for various transformations, including cyclopropanation, X–H insertion (X = C, N, O, S, B, etc.…”