Synthesis of Phenol–Pyridinium Salts Enabled by Tandem Electron Donor–Acceptor Complexation and Iridium Photocatalysis

Abstract

Herein, we describe a dual photocatalytic system to synthesize phenol−pyridinium salts using visible light. Utilizing both electron donor−acceptor (EDA) complex and iridium(III) photocatalytic cycles, the C−N cross-coupling of unprotected phenols and pyridines proceeds in the presence of oxygen to furnish pyridinium salts. Photocatalytic generation of phenoxyl radical cations also enabled a nucleophilic aromatic substitution (S N Ar) of a fluorophenol with an electron-poor pyridine. Spectroscopic experiments were conducted to probe the mechanism and reaction selectivity. The unique reactivity of these phenol−pyridinium salts were displayed in several derivatization reactions, providing rapid access to a diverse chemical space.

Amination of Phenols and Halophenols via Pyridinium–Iridium Dual Photocatalysis

“…Pyr1 was strategically selected to fulfill the criteria discussed above. Namely, pyridines bearing C2 substituents were unreactive as nucleophiles in our pyridination work . The CF 3 group ensures that pyr1 is a good acceptor for the phenols while not being too electron-poor as to be deactivated by direct reduction with the photocatalyst or to preclude protonation.…”

“…Using our prior pyridination conditions, the initial reaction discovery focused on the coupling of 2,4-dimethoxyphenol ( 1a ) and pyrazole ( 2a ) using Ir(ppy) 3 in HFIP (Scheme ). Our efforts started here as the Nicewicz reaction conditions with this phenol using acridinium photocatalyst di t -BuMesAcrBF 4 yielded no product .…”

“…Recently, Knowles and co-workers demonstrated the electron-withdrawing capabilities of the phenoxyl radical through Fe- and base-mediated S N Ar of halophenols with benzoates/carboxylates . Building upon our successful photocatalytic S N Ar pyridination involving 4-(trifluoromethyl)pyridine and 2,6-dimethyl-4-fluorophenol ( 1l ), the amination of a range of halophenols ( 1k–u ) was explored via activation of C–X bonds (Scheme ). Using the optimized C–H amination conditions, ortho - and para -S N Ar amination with pyrazole 2a occurred in excellent yields (up to 99%).…”

“…The recent emergence of electron donor–acceptor (EDA) photocatalysis has also enabled chemistries involving single-electron transfer (SET) events with low-energy visible light and without the need for photoredox catalysts. , This avenue of radical generation has largely been biased toward activation of an electron-poor component (acceptor) where an electron-rich component (donor) that acts as a catalyst/reagent is optimized. Recently, we disclosed the photochemical C–H and S N Ar pyridination of electron-rich phenols to furnish a variety of phenol–pyridinium salts (Figure C) . The reaction proceeded via EDA complexation between the phenol and the protonated pyridine (pyridinium) to form reactive phenoxyl radical cations, which are extremely electrophilic, upon light irradiation.…”