Copper-catalyzed trifluoromethylation of N-arylacrylamides “on water” at room temperature

Abstract

A copper-catalyzed intramolecular trifluoromethylation of arylacrylamides leads to oxindole derivatives, effected with stable and inexpensive Langlois' reagent (CF3SO2Na). These reactions proceed via a radical process in water at room temperature. The aqueous solution can be recycled.

Application of Langlois’ Reagent in Trifluoromethylation Reactions

“…In 2013, Lipshutz and co‐workers developed a practical and economical copper(II)‐catalyzed trifluoromethylation of N ‐arylacrylamides for the synthesis of a variety of CF 3 ‐containing oxindoles bearing a quaternary carbon center with CF 3 SO 2 Na and tert ‐butyl peroxide in the presence of Cu(NO 3 ) 2 ⋅2.5 H 2 O as catalyst (Scheme , a) 27a. Substrates bearing alkyl and aryl N ‐protecting groups provided good yields of the corresponding oxindoles, while a secondary aryl amide failed to give the desired product even after 20 h. Both electron‐withdrawing and electron‐donating groups at the para ‐position on the phenyl ring are well tolerated, and the desired products were obtained in good yields.…”

Electrophilic trifluoromethylation of carbonyl compounds and their nitrogen derivatives under copper catalysis

“…In the following year, the groups of Liang and Lipshutz, 38 as well as Lei 39 independently reported the same transformation using the combination of Langlois reagent (15) and TBHP in the presence of a catalytic amount of Cu(II) salt (Cu(NO 3 ) 2 and CuCl 2 , respectively). Notably, Lipshutz and co-workers have established reaction conditions that rely on water and ambient temperatures in air.…”

Trifluoromethylation of Alkenes with Concomitant Introduction of Additional Functional Groups

“…Chemie reaction using the photoredox catalyst [Ru(phen) 3 ]Cl 2 (72) instead of a copper salt (Scheme 21 b), [55] and Lipshutz et al reported a copper-catalyzed reaction using the combination of Langlois reagent and TBHP on water (Scheme 21 c). [56] Nevado et al recently demonstrated a trifluoromethylation coupled with a desulfonylative aryl migration/cyclization (Scheme 22 a). [57] Even though the trifluoromethylation of 3substituted acrylanilides usually provides a mixture of 4-and 6-substituted oxindole derivatives, Nevados method afforded a 6-substituted oxindole as the single product.…”