An aerobic copper-mediated domino process for the synthesis of 3-(trifluoromethylseleno)indoles

Abstract

An aerobic copper-mediated domino reaction for the synthesis of 3-(trifluoromethylseleno)indoles from trifluoromethylselenolation of N-Ts 2-alkynylaniline with [(bpy)CuSeCF3]2 is reported. This reaction proceeds through a sequential oxidation, alkyne coordination, and deprotonation...

Tf2O‐Catalyzed Tandem Cyclization/Trifluoromethylselenolation of Alkynes for Synthesis of CF3Se‐Containing Heterocycles

“…Subsequently, we turned our attention to exploring the compatibility of various protecting groups of anilines (Table 3). We were delighted to observe that substrates with different sulfonyl protecting groups, such as Ms, Ns and Tf, underwent the desired reaction to give the target products 4a – 4c in satisfactory yields, as did the Bz and Ac protected substrates, albeit with lower yields ( 4 d , 4 e ) which were not suitable in previous work [19b] . However, the conversion of free aniline almost failed ( 4 f ).…”

“…To demonstrate the utility of the protocol, we carried out the reaction of 1 a with 2 a on a gram‐scale, delivering the target product 3 a in almost quantitative yield (2.17 g, 95 %) with a slightly longer reaction time (5 h) (Scheme 3, Equation (1)). Furthermore, we performed the de‐protection of 3 a to obtain 2‐phenyl‐3‐trifluoromethylselenindole 4 f , [19b] which could not be obtained by direct cyclization of non‐activated 2‐alkynylaniline (Scheme 3, Equation (2)).…”

“…Encouraged by the above results, we applied our method to the synthesis of 3-[(trifluoromethyl)seleno]isoquinolines. Initially, we conducted the reaction under standard conditions and 55 % 19 F NMR yield of 8 a was obtained probably due to the lower reactivity of compound 7 [17] . To get a better yield, 1.0 equiv.…”

“…First, we conducted the reaction in the presence of 1.0 equiv. of butylated hydroxytoluene (BHT) and the desired product was obtained in 95 % 19 F NMR yield, indicating a non-radical process was involved (Eq. ( 1)).…”

“…[18] Weng and co-workers realized the synthesis of CF 3 Se-containing indoles via copper-mediated transformation (Scheme 1b, Equation (3)). [19] Yang and Du reported the synthesis of CF 3 Se-containing isocoumarins by engaging a stoichiometric amount of Tf 2 O as the activation reagent (Scheme 1b, Equation (4)). [20] However, the pre-generating of instable CF 3 SeCl and the requirement of transition metal catalyst/reagent, a stoichiometric amount of activation reagent and the rigorous high temperature limited their applications.…”