Azidoperfluoroalkanes: Synthesis and Application in Copper(I)‐Catalyzed Azide–Alkyne Cycloaddition

Abstract

We report an efficient and scalable synthesis of azidotrifluoromethane (CF N ) and longer perfluorocarbon-chain analogues (R N ; R =C F , C F , C F ), which enables the direct insertion of CF and perfluoroalkyl groups into triazole ring systems. The azidoperfluoroalkanes show good reactivity with terminal alkynes in copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), giving access to rare and stable N-perfluoroalkyl triazoles. Azidoperfluoroalkanes are thermally stable and the efficiency of their preparation should be attractive for discovery programs.

Synthesis, Stability and Reactivity of α‐Fluorinated Azidoalkanes

“…Longer-chain azidoperfluoroalkanes wasp repared in an analogousw ay (Scheme 14). [22,23] Azidopentafluoroethane formed using stable pentafluoroethyllithium (Scheme 15), [22] and tetrafluoroethylene-containing azides 6 via organomagnesium compounds generatedb yu sing Turbo-Grignard reagents (Scheme 16). [23]…”

Stereoselective Synthesis of (Z)‐β‐Enamido Triflates and Fluorosulfonates from N‐Fluoroalkylated Triazoles

“…They have been used for the preparation of different types of heterocycles, N-sulfonyl-containing compounds, [27] and for stereoselectives ynthesiso f2 ,2-diaryl or 2-alkyl-2-aryl-substituted N-sulfonyl enamides ( Figure 1B). [28][29][30][31][32][33] We have recently shown that N-fluoroalkyl triazoles prepared by a[ 3 + +2] cycloaddition of stable and safe azido(per)fluoroalkanes anda lkynes [34][35][36] are efficiently transformed to new N-fluoroalkyl heterocycles via rhodiumc arbenoids. [37,38] However,t he reactivity profiles of Nfluoroalkyl triazoles and N-sulfonyl triazoles are markedlyd ifferent.…”

Enamine‐Mediated Azide‐Ketone [3 + 2] Cycloaddition of Azidoperfluoroalkanes

“…Triazoles containing ethoxycarbonyl group at position 4 were subjected to basic hydrolysis and decarboxylation to yield 1,5‐disubstituted triazoles in good to high yields (Table ). The reaction complements the copper(I)‐catalyzed azide‐alkyne cycloaddition which gives access to 1,4‐disubstituted triazoles …”

“…In sharp contrast, strategies towards the synthesis of N ‐perfluoroalkyl compounds are scarce . Recently, we have reported a new method for the synthesis of azidoperfluoroalkanes (R F ‐N 3 ) which opened new possibilities to access N ‐perfluoroalkyl compounds …”