Synthesis of 5‐Trifluoromethyl‐1,4‐dihydro‐1,2,4‐triazines via Base‐mediated [3+3] Cycloaddition of Nitrile Imines and CF₃‐Imidoyl Sulfoxonium Ylides

Abstract

An approach for the construction of 5trifluoromethyl-1,4-dihydro-1,2,4-triazines has been developed via base-mediated [3 + 3] cycloaddition of in-situ generated nitrile imines and CF 3 -substituted imidoyl sulfoxonium ylides. The metal-free protocol is characterized by readily available starting materials, mild conditions, a broad substrate scope, high efficiency, good synthetic prospect, and scalability.

Rh(III)‐Catalyzed Cascade Cyclization of 2‐Aryl‐3H‐indoles and CF3‐Imidoyl Sulfoxonium Ylides Toward Trifluoroacetimidoyl‐Substituted 11H‐Isoindolo[2,1‐a]indoles

“…The presence of trifluoromethyl group can greatly alter the physicochemical and pharmacological properties of parent molecules. [9] As part of our continuous endeavours on investigating efficient approaches for the synthesis of trifluoromethyl-containing heterocycles using TFISYs, [10] we herein communicate our recent finding of Rh(III)-catalyzed CÀ H activation and cascade cyclization of 2-phenyl-3Hindoles and TFISYs to build trifluoroacetimidoylsubstituted 11H-isoindolo [2,1-a]indoles. TFISYs participated in this [4 + 1] annulation with silver as an external oxidant.…”

Rh(iii)-catalyzed C–H activation/annulation of N-carbamoylindoles with CF3-imidoyl sulfoxonium ylides for the divergent synthesis of trifluoromethyl-substituted (dihydro)pyrimidoindolones

“…8 CF 3 -substituted imidoyl sulfoxonium ylides (TFISYs) are a class of versatile trifluoromethyl synthons and have been successfully used to prepare a series of trifluoromethyl-functionalized heterocycles, including pyrroles, pyridones, pyrazoles, benzo[ b ][1,4]oxazines, 2,3-dihydrothiazoles, 1,4-dihydro-1,2,4-triazines, and so on. 9 In particular, TFISYs could be used as a stable carbene precursor in transition metal-catalyzed chelation-assisted C–H activation reactions to enable imidoylmethylation. Then, the imine–enamine tautomerization of the imidoylmethylated products endows them with multiple reactive sites in the following annulation reactions, which offers the possibility of chemodivergent reactions.…”

Formal (4+2) cycloaddition of azoalkenes with trifluoromethylimidoyl sulfoxonium ylides: synthesis of trifluoromethyl pyridazine derivatives

“…10 Moreover, metal-free cycloaddition reactions involving TFISYs have attracted great interest in recent years because they are operationally simple, highly efficient, and scalable, which enables the construction of diverse heterocyclic skeletons. Cheng 11 and Wu 12 independently reported (3+3) annulation reaction of TFISYs with cyclopropenones or hydrazonoyl chlorides, which produced CF 3 -containing pyridones or triazines, respectively (Scheme 1a). In addition, pyrroles and dihydrothiazoles bearing CF 3 units have been efficiently prepared using formal (3+2) cycloaddition chemistry involving TFISYs and β-ketoesters and α-enolic dithioesters, respectively (Scheme 1b).…”

“…Guided by previous literature reports, 6–14 Scheme 5 presents a tentative reaction mechanism for the chemistry developed in this study. The anionic carbon in the imidoyl sulfoxonium ylide 1a (as exemplified by resonance structure I ) initially nucleophilically attacks the CC bond of α,β-unsaturated hydrazone 2a to generate zwitterionic intermediate II .…”