Unveiling Extreme Photoreduction Potentials of Donor-Acceptor Cyanoarenes to Access Aryl Radicals from Aryl Chlorides

Abstract

Since the seminal work of Zhang in 2016, donor−acceptor cyanoarene-based fluorophores, such as 1,2,3,5tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN), have been widely applied in photoredox catalysis and used as excellent metalfree alternatives to noble metal Irand Ru-based photocatalysts. However, all the reported photoredox reactions involving this chromophore family are based on harnessing the energy from a single visible light photon, with a limited range of redox potentials from −1.92 to +1.79 V vs SCE. Here, we document the unprecedented discovery that this family of fluorophores can undergo consecutive photoinduced electron transfer (ConPET) to achieve very high reduction potentials. One of the newly synthesized catalysts, 2,4,5-tri(9H-carbazol-9-yl)-6-(ethyl(phenyl)amino)isophthalonitrile (3CzEPAIPN), possesses a long-lived (12.95 ns) excited radical anion form, 3CzEPAIPN•−*, which can be used to activate reductively recalcitrant aryl chlorides (Ered ≈ −1.9 to −2.9 V vs SCE) under mild conditions. The resultant aryl radicals can be engaged in synthetically valuable aromatic C−B, C−P, and C−C bond formation to furnish arylboronates, arylphosphonium salts, arylphosphonates, and spirocyclic cyclohexadienes. ■ INTRODUCTION Aryl chlorides are versatile building blocks in organic synthesis, being widely utilized as electrophilic partners in nucleophilic aromatic substitutions, in transition metal catalysis, and as precursors to organometallic complexes. Compared to the corresponding bromides or iodides, aryl chlorides are more abundant (Figure 1A), are frequently present in natural products and pharmaceutical molecules, and are often lower in cost and more stable, serving as excellent functional groups for late-stage derivatizations. Photoredox catalysis offers numerous opportunities for the convenient synthesis of active organic radical species through single electron transfer (SET), which is complementary to conventional two-electron processes. However, compared to aryl bromides and iodides, aryl chlorides in photoredox catalysis have been largely underexplored due to the high energetic barrier for C(sp)−Cl bond activation (PhCl at ∼97 kcal/mol). Upon absorption of a photon, the excited photoredox catalyst promotes the single-electron reduction of aryl halides. Subsequent C−X bond cleavage delivers carboncentered radicals, which can participate in a plethora of transformations. The reaction scope is therefore restricted by the energy of a photon. Visible light energy (e.g., a 440 nm blue photon possesses a maximum driving force of 2.8 eV) is typically diminished by 25%−50% through vibrational relaxation, internal conversion, and intersystem crossing, which is difficult to activate challenging nonactivated aryl chlorides, that normally requires carcinogenic high-energy ultraviolet (UV) light. Several strategies have been developed during the past several years to address these challenges and enable the activation of aryl chlorides under visible light irradiation and Received: June 9, 2021 Article pubs.acs.org/JACS © XXXX American Chemical Society A https://doi.org/10.1021/jacs.1c05994 J. Am. Chem. Soc. XXXX, XXX, XXX−XXX D ow nl oa de d vi a T IA N JI N U N IV o n A ug us t 2 2, 2 02 1 at 1 5: 15 :2 1 (U T C ). Se e ht tp s: //p ub s. ac s. or g/ sh ar in gg ui de lin es f or o pt io ns o n ho w to le gi tim at el y sh ar e pu bl is he d ar tic le s.