Recent advances in pyrazole synthesis employing diazo compounds and synthetic analogues

Abstract

Pyrazole is an essential structural component of many pharmaceuticals and agrochemicals. The synthesis of pyrazoles has been a subject of intense research for several decades. Many transformations are now available...

Regioselective [3 + 2] cycloaddition of di/trifluoromethylated hydrazonoyl chlorides with fluorinated nitroalkenes: a facile access to 3-di/trifluoroalkyl-5-fluoropyrazoles

“…1 In this context, tremendous efforts have been devoted to the development of robust and versatile synthetic methods to incorporate a single fluorine atom or fluoroalkyl groups into pyrazole rings. 2,3 In sharp contrast, the synthesis of pyrazoles bearing two different fluorinated groups remains underdeveloped, 4 despite their potentially enhanced potency in drug discovery. Leroux and co-workers described several facile strategies to synthesize a diverse set of bis(fluoroalkyl)pyrazoles based on fluoroalkyl amino reagents (FARs).…”

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 ].…”

[4+1] cyclization of α-diazo esters and mesoionic N-heterocyclic olefins

“…Diazo-carboxylic esters are commonly used electron-deficient 1,3-dipoles in these [3+2] cycloaddition reactions. 3,4 For example, a diazo-carboxylic ester and an electron-rich olefin, such as an enamine, can react to form a pyrazole ring. 4 This reaction was originally proposed to proceed via a concerted mechanism.…”

“…3,4 For example, a diazo-carboxylic ester and an electron-rich olefin, such as an enamine, can react to form a pyrazole ring. 4 This reaction was originally proposed to proceed via a concerted mechanism. However, recent studies showed that this reaction may proceed through a stepwise pathway (Scheme 1), starting with a nucleophilic addition of the enamine olefinic carbon onto the terminal nitrogen of the diazo motif, where the nucleophilicity of the dipolarophile and the electrophilicity of the 1,3-dipole are crucial.…”