Synthesis of Arylamines via Aminium Radicals

Abstract

Arylamines constitute the core structure of many therapeutic agents, agrochemicals, and organic materials. The development of methods for the efficient and selective construction of these structural motifs from simple building blocks is desirable but still challenging. We demonstrate that protonated electron‐poor O‐aryl hydroxylamines give aminium radicals in the presence of Ru(bpy)3Cl2. These highly electrophilic species undergo polarized radical addition to aromatic compounds in high yield and selectivity. We successfully applied this method to the late‐stage modification of chiral catalyst templates, therapeutic agents, and natural products.

Continuous‐Flow Electrosynthesis of Benzofused S‐Heterocycles by Dehydrogenative C−S Cross‐Coupling

“…These results demonstrated that TFAand Sc(OTf) 3 were helpful for promoting the oxidation of the thioamide substrate and in the meanwhile avoiding overoxidation of the heterocyclic product. [18] In the reaction mixture,T FA probably undergoes ligand exchange with Sc(OTf) 3 to generate stronger acid TfOH, which increases the concentration of the protonated form (II). One-electron anodic oxidation of the thioamide substrate I leads to the formation of the thioamidyl radical cation II, [17] which is in equilibrium with the neutral thioamidyl radical III.R adical cyclization followed by oxidative rearomatization afford the final product V.T he cyclization via II is expected to be more efficient than the neutral species III because the S-radical in II is more electrophilic than that in III,a nd thus more reactive toward the phenyl ring.…”

“…Briefly,t he substituent on the thioamide nitrogen atom tolerated iPr (15), Cy (16), and tBu (17). Substrates bearing electron-rich and electrondeficient phenyl rings all reacted smoothly to afford the desirable N,S-heterocycles (18)(19)(20)(21)(22)(23)(24)(25)(26). Besides the methanesulfonyl (Ms) group, p-tulenesulfonyl (Ts; 27)a nd acyl groups (28-33)were suitable substituents on the nitrogen linker.…”

“…One-electron anodic oxidation of the thioamide substrate I leads to the formation of the thioamidyl radical cation II, [17] which is in equilibrium with the neutral thioamidyl radical III.R adical cyclization followed by oxidative rearomatization afford the final product V.T he cyclization via II is expected to be more efficient than the neutral species III because the S-radical in II is more electrophilic than that in III,a nd thus more reactive toward the phenyl ring. [18] In the reaction mixture,T FA probably undergoes ligand exchange with Sc(OTf) 3 to generate stronger acid TfOH, which increases the concentration of the protonated form (II). With aslow cyclization, III can undergo dimerization and hydrolysis to give desulfurization product such as 3.…”

A Retrosynthetic Approach for Photocatalysis

“…Furthers alternatives were developed by Liu and co‐workers starting from aryl azides, Sanford and co‐workers who started from phthalimide trifluoroacetamides instead of pyridinium triflates yielding aryl phthalimides and by Leonori and co‐workers who started from O ‐dinitroaryl hydroxylamines yielding arylamines (e.g. piperidines) . In addition to this method, Leonori and co‐workers recently contributed another procedure for the direct amination of arenes starting from simple, unfunctionalized secondary amines …”

Hydroxylamine Derivatives as Nitrogen‐Radical Precursors in Visible‐Light Photochemistry

“…Continuing this line of investigation, we have recently identified conditions for the preparation of aryl amines from electron‐poor O ‐aryl hydroxylamines ( 43 , Ar=2,4‐(NO 2 ) 2 ‐C 6 H 3 ) . In this case, the strong Bronsted acid HClO 4 was required to access the highly electrophilic aminium radicals.…”