Site-Selective Synthesis of N-Benzyl 2,4,6-Collidinium Salts by Electrooxidative C–H Functionalization

Abstract

N-alkylpyridinium salts are versatile pseudohalides for SET-mediated cross couplings. However, the common 2,4,6triphenylpyridinium salt is plagued by poor atom economy and high cost of synthesis. Thus, there is a growing need for more practical scaffolds and innovative strategies for pyridinium salt formation. Herein, we report the synthesis of benzylic 2,4,6collidinium salts via electrooxidative C−H functionalization. This method provides a complementary approach to tradtional strategies relying on substitution and condensation of prefunctionalized substrates.

I(III)-Mediated Arene C–H Amination Using (Hetero)Aryl Nucleophiles

“…In considering the extension of HGT reactions to C(sp 2 )–N bond formation, we recognized that an N -HVI HGT strategy could serve as a convenient and potentially general approach to I(III)-mediated arene amination (Scheme B). The N-heterocycles would act as “oxidatively masked” nucleophilic amines, and the product would be shielded from overoxidation as a cationic pyridinium salt ( 3 ). , Pioneering work by Yoshida and recent reports by Carreira, Ritter, and Sanford , have achieved oxidative arene amination via (hetero)aryl nucleophiles through the use of electrochemistry, photoredox catalysis, or EDA complexes, and we demonstrated a complementary benzylic-selective C–H collidination, demonstrating the utility of such an approach.…”

“…Further support was found in the reaction of 4-Me-anisole wherein, in addition to arylpyridinium 17 and diaryliodonium salt 18 , benzylic pyridinium 19 was also observed (Scheme B). Mechanistically, the formation of 19 can be explained via deprotonation of a radical cation intermediate to generate an electrophilic benzylic position, followed by nucleophilic trapping. ,− An alternative hypothesis was that an S N Ar reaction on an initially formed diaryliodonium salt could give the observed pyridinium products; however, this seemed unlikely as it would require nucleophilic attack on the more electron-rich aromatic. , This possibility was further discounted as prolonged heating of anisole-derived iodonium 19 with excess pyridine yielded none of the corresponding pyridinium ( 20 ) (Scheme C).…”

Synthesis of 3‐Aminopiperidines via I(III)‐Mediated Olefin Diamination with (Hetero)aryl Nucleophiles

“…Recently, our laboratory has developed “heterocyclic group transfer” (HGT) reactions of N ‐heterocyclic‐ligated I(III) reagents, or N ‐HVIs ( 7 ), to achieve olefin aminolactonization [46] and arene C−H amination [47] . In this approach, the heteroarene nucleophiles serve as “oxidatively masked” amines, shielding them from competitive degradation pathways.…”

Pulsed electrolysis: enhancing primary benzylic C(sp3)–H nucleophilic fluorination

“…Hence, in contrast to secondary and tertiary, the generation of primary benzylic cations by electrochemical oxidation and their functionalisation has been reported very few times, and as such is limited to the use of highly electron-rich substrates, solvent level nucleophile, or a cation-pool strategy. [18][19][20][21][22][23] The introduction of alternative electrolysis waveforms has been demonstrated as a tool for facilitating unique reactivity (Fig. 1C).…”

“…Hence, in contrast to secondary and tertiary, the generation of primary benzylic cations by electrochemical oxidation and their functionalisation has been reported very few times, and as such is limited to the use of highly electron-rich substrates, solvent level nucleophile, or a cation-pool strategy. 18–23…”