Copper‐Catalyzed Three‐Component Oxytrifluoromethylation of Alkenes with Sodium Trifluoromethanesulfinate and Hydroxamic Acid

Abstract

Radical paths: The title reaction of olefins with NaSO2CF3 and N‐hydroxy‐N‐phenylacetamide at room temperature is described for the first time (see scheme). This reaction provides a practical and convenient route to a series of trifluoromethylated alcohols bearing a wide range of functional groups.

Catalyst‐Free Oxytrifluoromethylation of Alkenes through Paired Electrolysis in Organic‐Aqueous Media

“…A one‐pot procedure using the Umemoto reagent and Ir(ppy) 3 as photoredox catalyst was described by Koike and Akita . Jiang and Qing combined sodium triflinate and 6 equiv t BuOOH (to generate CF 3 radicals) with hydroxamic acid to form another oxyamine intermediate . The corresponding alcohol was then obtained after reducing the N−O bond with Mo(CO) 6 .…”

“…[14] Jiang and Qing combined sodium triflinate and 6equiv tBuOOH (to generate CF 3 radicals) with hydroxamic acid to form another oxyamine intermediate. [15] The corresponding alcohol was then obtaineda fter reducing the NÀOb ond with Mo(CO) 6 . [15] Notably,t hese methods utilize expensive CF 3 sources, [13,14] stoichiometric amounts of oxidizing or reducing agents [13,15] or expensive metal catalysts, [14] which limits their applicability in large-scale synthesis.…”

Radical aryl migration enables diversity-oriented synthesis of structurally diverse medium/macro- or bridged-rings

“…2), we turned our attention to target benzannulated eight-membered ketone 4N and tested substrate 1N with a five-membered ring under the standard conditions. To our disappointment, such substrate preferentially underwent competitive 1,2-oxytrifluoromethylation3738 to give product 4N′ in 65% yield with good diastereoselectivity (14:1 d.r.) (Supplementary Table 3).…”

“…Nonetheless, the realization of such cascade sequence reactions remains an underdeveloped process. Several challenges are associated with the development of this reaction, such as (1) the unfavourable kinetic and/or thermodynamic factors to realize regioselective medium ring formation over other competitive 1,2-difunctionalizations of alkenes with oxygen-based nucleophiles35363738, (2) the compatibility between unactivated alkenyl substrates and various radical precursors with different reactivity properties, (3) the identification of mild reaction conditions to achieve high degree of enantiocontrol through remote chirality transfer strategy.…”

Synthetic Approaches to Trifluoromethoxy‐Substituted Compounds

“…In fact, two reactions compete with the desired oxidative coupling, namely the formation of the corresponding benzenesulfonate of the phenol starting material and C-trifluoromethylation of the aromatic ring. [29] 3.3. [28a] Extending this approach to N-heteroaromatic phenols initially failed, probably owing to coordination of the nitrogen atom to the metal center.…”