The serendipitous effect of KF in Ritter reaction: Photo-induced amino-alkylation of alkenes

Abstract

Summary Ritter reaction has been recognized as an elegant strategy to construct the C−N bond. Its key feature is forming the carbocation for nucleophilic attack by nitriles. Herein, we report a complementary visible-light-induced three-component Ritter reaction of alkenes, nitriles, and α -bromo nitriles/esters, thereby providing mild and rapid access to various γ -amino nitriles/acids. Mechanistic studies indicated that traceless fluoride relay, transforming KF into imidoyl fluoride intermediate, is critical for the efficient reaction switch from atom transfer radical addition (ATRA) to the Ritter reaction. This approach to amino-alkylation of alkenes is chemoselective and operationally simple.

Zinc acetate-promoted blocking of the ATRA process with alkyl halides enabling photochemical alkylamination of olefins

“…We suspect that the superior productivity of the present protocol might be attributed by the multiple pivotal roles of Zn(OAc) 2 , including activating alkyl halide substrates, suppressing side reactions by scavenging halide anions, and accelerating the nitrile addition to the carbocation. 21 According to our studies and literature reports 10,14 we believe that the carboamination proceeds via a photocatalytic oxidative radical-polar crossover cycle starting with the SET reduction of I (Scheme 1B).…”

“…Recently, Chen's group has utilized neutral bromo nitriles/esters in carboamination of alkenes by trapping the nitrilium ion ( V , Scheme 1B) with KF to a hydrolyzable imidoyl fluoride intermediate. 14 Although this strategy managed the ATRA issue by sequentially engaging it as a new alkylradical precursor to deliver desired products, the reaction conditions are not convenient (using an Ir-catalyst, and glove box setup) and the substrate scope is only limited to vinyl arenes.…”

“…To the best of our knowledge, no prior photo-redox Ritter-type carboamination reactions have been successful with this substrate class. 10,14 To further exhibit the good compatibility of this strategy, bio- and drug-relevant complex molecules derived from estrone, valine, ciprofloxacin, vitamin E and Naproxen were also functionalized in this process ( 4u–y ).…”

Photocatalytic dehydrations for the Ritter reaction

“…5 Generally, most of the developed procedures rely on photochemical radical–polar crossover strategies using alkenes and radical precursors as substrates (Scheme 1A). 6 Recently, Lambert and co-workers reported an electrophotocatalytic Ritter reaction of benzylic compounds without using stoichiometric oxidants (Scheme 1B). 7 On the other hand, benzyl alcohols are cheap and readily available.…”

Photo‐Induced Construction of N‐Aryl Amides by Fe Catalysis

“…[14] Very recent, Bao group reported an ironcatalyzed nitrene transfer reactions under light irradiation. [15] Inspired by our long-standing interests in photo-promoted organic transformation, [16] we herein developed a photoinduced electrophilic amidation with stable N-methoxyamides www.eurjoc.org and boronic acids under Fe catalysis. Different from the previous nitrene intermediate mechanism, this electrophilic amidation is enabled by N-radical through intramolecular MLCT/SET process (Scheme 1D).…”