Substantial development in visible-light catalysis has been witnessed over recent years [1-3]. Due to the unique ability of visible-light harvesting, Ru(Ⅱ) [4-11] and Ir(Ⅲ) [12-17] complexes, organic dyes [18-21] and semiconductors [22, 23] have been successfully used in single electron transfer (SET) to activate a variety of functional groups. In this regard, the umpolung conversion of C=X double bonds (X = O, N) is highly attractive. Classical polarity inversion of aldehydes, ketones and imines usually requires excess metals or unstable strong reducing agents under harsh conditions, meaning that only a narrow range of substrates are compatible [24, 25], greatly limiting their subsequent transformation. In contrast to using traditional methods, these C=X double bonds (X = O, N) can easily obtain one electron via visible-light catalysis to be converted into a practical nucleophilic intermediate. In 2013, Knowles et al. [26, 27] reported an intramolecular reductive coupling between ketones and hydrazones or electron-deficient olefins under visible-light catalysis via proton coupled electron transfer. In the same year, MacMillan et al. [28, 29] demonstrated the coupling of ketones and amines with activated C-H bonds, including benzylic ethers with the β-position of enamines generated in situ. More recently, Rueping et al.[30, 31] realized the dimerization of C=X double bonds (X = O, N) and the cross coupling of tertiary amines and ketones assisted by photo-induced two-center/three-electron intermediates. Xiao et al. [32] expanded this cross coupling reaction to include secondary amines. Chen et al. [33] demonstrated the visible-light-induced polarity-reversed allylation of aldehydes, ketones and imines with electron-withdrawing allyl sulfones. Furthermore, Ngai et al. [34] described reductive coupling of these polar C=X double bonds (X = O, N) with weak electrophilic alkenylpyridines through chelation with a lanthanide. Visible-light-induced polarity inversion of C=X bonds (X = O, N) has demonstrated the potential to synthesize alkyl alcohols and amines. We were keen to investigate if a visible-light strategy could be applied to the construction of aryl-substituted products, which are generally synthesized using air-or water-sensitive Grignard reagents under thermal conditions (Scheme 1). This would provide a simple and mild way to generate aryl alcohols and amines, with no need for harsh conditions and sensitive reagents.

¹H NMR spectra were recorded using a Bruker Avance DPX 400 MHz instrument with tetramethylsilane (TMS) as the internal standard. ¹³C NMR spectra were obtained at 100 MHz and referenced to the internal solvent signals. Mass spectra were recorded using a Trio-2000 GC-MS spectrometer. Commercially available reagents and solvents were used without further purification. Blue LEDs (3 W, λ = 450 ± 10 nm, 145 lm @ 700 mA) were used as the irradiation light.

The aldehyde (1.0 mmol) was added to a solution of aryl amine (1.0 mmol) in anhydrous Et₂O (20 mL) in the presence of molecular sieves (4 Å 1.6 mm pellets, 7 g). The reaction was performed at room temperature (RT) under magnetic stirring and monitored by TLC. When the reaction was complete, the molecular sieves were removed by filtration, and the solvent was removed under vacuum. The residue was recrystallized from Et₂O/n-hexane to afford the imines directly as pure (E) products.

A 10-mL Pyrex tube equipped with a magnetic stir bar was charged with 1, 4-dicyanobenzene (1, 4-DCB) (25.6 mg, 0.2 mmol), fac-Ir(ppy)₃ (2.6 mg, 2 mol%), TEMPO (0.4 mmol, 2 equiv.) and DMSO (2 mL). The Pyrex tube was sealed with rubber plug and then deaerated by bubbling Ar for 15 min. benzaldehyde (30.5 μL, 0.3 mmol) and DIPEA (52.4 μL, 0.3 mmol) were added. The reaction system was irradiated with blue LEDs (λ = 450 ± 10 nm) for 12 h at RT. When the reaction was complete, the aqueous solution was extracted with ethyl acetate (5 mL × 3). The organic extracts were combined, washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under vacuum, then diphenylacetonitrile (23.2 mg) was added as an internal standard and the yield (19%) was detected by ¹H NMR.

A 10-mL Pyrex tube equipped with a magnetic stir bar was charged with 1, 4-DCB (25.6 mg, 0.2 mmol), fac-Ir(ppy)₃ (2.6 mg, 2 mol%) and DMSO (2 mL). The Pyrex tube was sealed with rubber plug and then deaerated by bubbling Ar for 15 min, then benzaldehyde (30.5 μL, 0.3 mmol) and DIPEA (52.4 μL, 0.3 mmol) were added. The reaction system was irradiated with blue LEDs (λ = 450 ± 10 nm) for 12 h at RT. When the reaction was complete, the aqueous solution was extracted with ethyl acetate (5 mL × 3). The organic extracts were combined, washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under vacuum and the residue was purified by chromatography on silica gel (petroleum ether: ethyl acetate = 3:1) to afford the desired product.

4-(Hydroxy(phenyl)methyl)benzonitrile (3): colorless oil, isolated yield: 83%. ¹H NMR (400 MHz, CDCl₃) δ 7.59 (d, J = 8.4 Hz, 2H), 7.49 (d, J = 8.2 Hz, 2H), 7.38-7.26 (m, 5H), 5.83 (s, 1H), 2.65 (s, 1H). ¹³C NMR (100 MHz, CDCl₃) 149.01, 142.93, 132.34, 128.96, 128.36, 127.12, 126.78, 118.91, 111.18, 75.69. HRMS (EI) calculated for C₁₄H₁₁NO [M-H]⁺: 208.0762, found: 208.0761.

4-(Hydroxy(phenyl)methyl)-2-methylbenzonitrile and 4-(hydroxyl(phenyl)methyl)-3-methylbenzonitrile (4): colorless oil, isolated yield: 82%, the ratio of regioselectivity = 1.47. ¹H NMR (400 MHz, CDCl₃) δ 7.76 (d, J = 8.0 Hz, 0.40 H), 7.58-7.50 (m, 1.00 H), 7.41-7.21 (m, 6.60 H), 5.95/5.80 (s, 1.00H), 2.53 (d, J = 2.7 Hz, 0.60 H), 2.50 (s, 1.80H), 2.45 (d, J = 3.1 Hz, 0.40H), 2.20 (s, 1.20H). ¹³C NMR (100 MHz, CDCl₃) δ 148.80, 146.78, 143.04, 142.28, 141.65, 136.64, 133.87, 132.74, 130.04, 128.94, 128.93, 128.40, 128.30, 128.11, 127.40, 126.92, 126.75, 124.36, 119.06, 118.22, 111.68, 111.22, 75.75, 73.22, 20.66, 19.33. HRMS (EI) calculated for C₁₅H₁₃NO [M]⁺: 223.0997, found: 223.0999.

Phenyl(4-(phenylsulfonyl)phenyl)methanol (5): white solid, isolated yield: 52%. ¹H NMR (400 MHz, CDCl₃) δ 7.97-7.79 (m, 4H), 7.54-7.45 (m, 5H), 7.37-7.22 (m, 5H), 5.83 (s, 1H), 2.59 (s, 1H). ¹³C NMR (100 MHz, CDCl₃) δ 149.46, 142.96, 141.68, 140.52, 133.30, 129.39, 128.92, 128.29, 127.94, 127.76, 127.33, 126.77, 75.69. HRMS (ESI) calculated for C₁₉H₁₆O₃S [M+Na]⁺: 347.0712, found: 347.0709.

Methyl 4-(hydroxy(phenyl)methyl)benzoate (6): colorless oil, isolated yield: 48%. ¹H NMR (400 MHz, CDCl₃) δ 7.97 (d, J = 8.3 Hz, 2H), 7.44 (d, J = 8.2 Hz, 2H), 7.34-7.24 (m, 5H), 5.83 (s, 1H), 3.87 (s, 3H), 2.68 (s, 1H). ¹³C NMR (100 MHz, CDCl₃) δ 167.07, 148.89, 143.41, 129.88, 129.32, 128.78, 128.03, 126.77, 126.45, 75.99, 52.19. HRMS (EI) calculated for C₁₅H₁₄O₃ [M]⁺: 242.0943, found: 242.0941.

5-(Hydroxy(phenyl)methyl)isobenzofuran-1(3H)-one  (7): white solid, isolated yield: 42%. ¹H NMR (400 MHz, CDCl₃) δ 7.80 (d, J = 7.9 Hz, 1H), 7.55 (s, 1H), 7.51 (d, J = 7.9 Hz, 1H), 7.35-7.35 (m, 5H), 5.92 (s, 1H), 5.24 (s, 2H), 2.94 (s, 1H). ¹³C NMR (100 MHz, CDCl₃) δ 171.14, 150.88, 147.13, 143.16, 128.93, 128.29, 127.70, 126.76, 125.75, 124.81, 119.83, 75.90, 69.79. HRMS (EI) calculated for C₁₅H₁₂O₃ [M]⁺: 240.0786, found: 240.0790.

Phenyl(1H-pyrrolo[2, 3-b]pyridin-4-yl)methanol (8): yellow oil, isolated yield: 82%. ¹H NMR (400 MHz, CDCl₃) δ 10.50 (s, 1H), 8.13 (d, J = 5.0 Hz, 1H), 7.37 (d, J = 7.1 Hz, 2H), 7.26-7.09 (m, 5H), 6.38 (d, J = 3.5 Hz, 1H), 6.12 (s, 1H), 3.37 (s, 1H). ¹³C NMR (100 MHz, CDCl₃) δ 148.83, 145.19, 142.85, 128.74, 128.07, 126.98, 125.13, 118.06, 112.84, 99.84, 74.49. HRMS (ESI) calculated for C₁₄H₁₂N₂O [M+H]⁺: 225.1028, found: 225.1016.

Phenyl(pyridin-4-yl)methanol (9): yellow solid, isolated yield: 99%. ¹H NMR (400 MHz, CDCl₃) δ 8.25 (dd, J = 4.6, 1.6 Hz, 2H), 7.30-7.23 (m, 7H), 5.70 (s, 1H). ¹³C NMR (100 MHz, CDCl₃) δ 153.83, 149.05, 143.16, 128.71, 128.01, 126.87, 121.53, 74.59. HRMS (ESI) calculated for C₁₂H₁₁NO [M+H] ⁺: 186.0919, found: 186.0911.

(2, 6-Dimethylpyridin-4-yl)(phenyl)methanol (10): yellow oil, isolated yield: 99%. ¹H NMR (400 MHz, CDCl₃) δ 7.48-7.20 (m, 5H), 6.96 (s, 2H), 5.68 (s, 1H), 4.05 (s, 1H), 2.42 (s, 6H). ¹³C NMR (100 MHz, CDCl₃) δ 157.81, 153.63, 143.25, 128.75, 128.06, 126.85, 118.07, 74.94, 24.30. HRMS (ESI) calculated for C₁₄H₁₅NO [M+H]⁺: 214.1232, found: 214.1224.

Isoquinolin-1-yl(phenyl)methanol (11): yellow oil, isolated yield: 86%. ¹H NMR (400 MHz, CDCl₃) δ 8.53 (d, J = 5.6 Hz, 1H), 7.95 (d, J = 8.4 Hz, 1H), 7.82 (d, J = 8.1 Hz, 1H), 7.64-7.60 (m, 2H), 7.49-7.45 (m, 1H), 7.41-7.16 (m, 5H), 6.36 (s, 1H), 6.15 (s, 1H). ¹³C NMR (100 MHz, CDCl₃) δ 159.33, 143.47, 140.14, 136.71, 130.38, 128.83, 127.97, 127.79, 127.57, 127.50, 125.34, 124.92, 121.20, 72.70. HRMS (ESI) calculated for C₁₆H₁₃NO [M+H]⁺: 236.1075, found: 236.1067.

4-((4-Chlorophenyl)(hydroxy)methyl)benzonitrile   (12): white solid, isolated yield: 55%. ¹H NMR (400 MHz, CDCl₃) δ 7.61 (d, J = 8.1 Hz, 2H), 7.48 (d, J = 8.1 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H), 7.27 (d, J = 7.7 Hz, 2H), 5.84 (s, 1H), 2.55 (s, 1H). ¹³C NMR (100 MHz, CDCl₃) δ 148.55, 141.35, 134.22, 132.50, 129.13, 128.14, 127.13, 118.79, 111.56, 75.05. HRMS (ESI) calculated for C₁₄H₁₀ClNO [M-H]⁺: 242.0373, found: 242.0377.

4-(Hydroxy(4-methoxyphenyl)methyl)benzonitrile  (13): white solid, isolated yield: 83%. ¹H NMR (400 MHz, CDCl₃) δ 7.60 (d, J = 8.1 Hz, 2H), 7.49 (d, J = 8.0 Hz, 2H), 7.22 (d, J = 8.4 Hz, 2H), 6.86 (d, J = 8.4 Hz, 2H), 5.81 (s, 1H), 3.78 (s, 3H), 2.45 (s, 1H). ¹³C NMR (100 MHz, CDCl₃) δ 159.66, 149.26, 135.24, 132.31, 128.21, 127.03, 118.97, 114.35, 111.10, 75.30, 55.43. HRMS (ESI) calculated for C₁₅H₁₃NO₂ [M-H]⁺: 238.0863, found: 238.0871.

4-(Hydroxy(thiophen-2-yl)methyl)benzonitrile (14): yellow oil, isolated yield: 68%. ¹H NMR (400 MHz, CDCl₃) δ 7.64 (d, J = 8.1 Hz, 2H), 7.56 (d, J = 8.2 Hz, 2H), 7.29 (d, J = 5.0 Hz, 1H), 6.98-6.94 (m, 1H), 6.93-6.92 (m, 1H), 6.10 (s, 1H), 2.76 (d, J = 17.4 Hz, 1H). ¹³C NMR (100 MHz, CDCl₃) δ 148.23, 146.83, 132.44, 126.99, 126.31, 125.56, 118.83, 111.67, 71.53. HRMS (EI) calculated for C₁₂H₉NOS [M]⁺: 215.0405, found: 215.0408.

4-(Hydroxy(naphthalen-2-yl)methyl)benzonitrile  (15): white solid, isolated yield: 62%. ¹H NMR (400 MHz, CDCl₃) δ 7.87-7.79 (m, 4H), 7.66-7.44 (m, 6H), 7.37 (m, 1H), 6.02 (s, 1H), 2.52 (s, 1H). ¹³C NMR (100 MHz, CDCl₃) δ 148.78, 140.19, 133.32, 133.24, 132.41, 129.02, 128.16, 127.88, 127.26, 126.68, 126.57, 125.74, 124.48, 118.92, 111.35, 75.88. HRMS (EI) calculated for C₁₈H₁₃NO [M]⁺: 259.0997, found: 259.0994.

4-(1-Hydroxy-1-phenylethyl)benzonitrile (18): colorless oil, isolated yield: 82%. ¹H NMR (400 MHz, CDCl₃) δ 7.58 (d, J = 8.2 Hz, 2H), 7.53 (d, J = 8.2 Hz, 2H), 7.42-7.23 (m, 5H), 2.38 (s, 1H), 1.95 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 153.45, 146.75, 132.13, 128.65, 127.74, 126.66, 125.93, 118.96, 110.77, 76.08, 30.66. HRMS (EI) calculated for C₁₅H₁₃NO [M]⁺: 223.0997, found: 223.0995.

4-(1-(4-Ethylphenyl)-1-hydroxyethyl)benzonitrile  (19): colorless oil, isolated yield: 87%. ¹H NMR (400 MHz, CDCl₃) δ 7.58 (d, J = 8.4 Hz, 2H), 7.53 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.1 Hz, 2H), 7.17 (d, J = 8.1 Hz, 2H), 2.63 (q, J = 7.6 Hz, 2H), 2.26 (s, 1H), 1.93 (s, 3H), 1.22 (t, J = 7.6 Hz, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 153.68, 144.08, 143.87, 132.10, 128.13, 126.64, 125.95, 119.03, 110.68, 76.00, 30.72, 28.51, 15.53. HRMS (MALDI-TOF) calculated for C₁₇H₁₇NO [M+Na]^+: 274.1208, found: 274.1202.

4-(1-Hydroxy-2, 3-dihydro-1H-inden-1-yl)benzonitrile (20): colorless oil, isolated yield: 81%. ¹H NMR (400 MHz, CDCl₃) δ 7.61 (d, J = 8.3 Hz, 2H), 7.51 (d, J = 8.3 Hz, 2H), 7.38-7.29 (m, 2H), 7.25-7.21 (m, 1H), 7.01 (d, J = 7.6 Hz, 1H), 3.23-3.21 (m, 1H), 3.06-2.93 (m, 1H), 2.53-2.40 (m, 2H), 2.21 (s, 1H). ¹³C NMR (100 MHz, CDCl₃) δ 152.03, 147.19, 144.21, 132.05, 129.21, 127.55, 126.70, 125.33, 123.99, 119.08, 110.82, 85.41, 44.98, 30.07. HRMS (EI) calculated for C₁₆H₁₃NO [M]⁺: 235.0997, found: 235.0999.

4-(1-(4-Chlorophenyl)-1-hydroxyethyl)benzonitrile  (21): white solid, isolated yield: 76%. ¹H NMR (400 MHz, CDCl₃) δ 7.60 (d, J = 8.3 Hz, 2H), 7.51 (d, J = 8.2 Hz, 2H), 7.31 (m, 4H), 2.35 (s, 1H), 1.94 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 152.86, 145.31, 133.65, 132.26, 128.75, 127.43, 126.61, 118.83, 111.08, 75.72, 30.69. HRMS (EI) calculated for C₁₅H₁₂ClNO [M]⁺: 257.0607 found: 257.0610.

4-(1-Hydroxy-1-(4-methoxyphenyl)ethyl)benzonitrile (22): colorless oil, isolated yield: 76%. ¹H NMR (400 MHz, CDCl₃) δ 7.58 (d, J = 8.4 Hz, 2H), 7.52 (d, J = 8.5 Hz, 2H), 7.29 (d, J = 8.8 Hz, 2H), 6.85 (d, J = 8.8 Hz, 2H), 3.79 (s, 3H), 2.29 (d, J = 11.9 Hz, 1H), 1.92 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 159.07, 153.80, 139.00, 132.09, 127.30, 126.60, 119.02, 113.92, 110.64, 75.80, 55.41, 30.82. HRMS (EI) calculated for C₁₆H₁₅NO₂ [M]⁺: 253.1103, found: 253.1106.

4-(Cyclopropyl(hydroxy)(phenyl)methyl)benzonitrile (23): white solid, isolated yield: 67%. ¹H NMR (400 MHz, CDCl₃) δ 7.59 (d, J = 8.3 Hz, 2H), 7.53 (d, J = 8.2 Hz, 2H), 7.44 (d, J = 8.0 Hz, 2H), 7.37-7.28 (m, 3H), 1.96 (s, 1H), 1.61-1.58 (m, 1H), 0.76-0.64 (m, 1H), 0.60-0.41 (m, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 152.78, 146.16, 131.89, 128.49, 127.90, 127.49, 127.07, 119.06, 110.82, 76.96, 21.54, 2.53, 1.38. HRMS (EI) calculated for C₁₇H₁₅NO [M]⁺: 249.1154, found: 249.1156.

4-(Phenyl(phenylamino)methyl)benzonitrile (24): pale yellow oil, isolated yield: 83%. ¹H NMR (400 MHz, CDCl₃) δ 7.63 (d, J = 8.3 Hz, 2H), 7.55 (d, J = 8.1 Hz, 2H), 7.40-7.31 (m, 5H), 7.16 (t, J = 7.6 Hz, 2H), 6.76 (t, J = 7.3 Hz, 1H), 6.54 (d, J = 8.2 Hz, 2H), 5.55 (s, 1H), 4.26 (s, 1H). ¹³C NMR (100 MHz, CDCl₃) δ 148.30, 146.83, 141.93, 132.69, 129.35, 129.21, 128.18, 128.08, 127.71, 118.87, 118.42, 113.65, 111.26, 63.01. HRMS (MALDI-TOF) calculated for C₂₀H₁₆N₂ [M+H]⁺: 285.1392, found: 285.1388.

4-((Phenylamino)(p-tolyl)methyl)benzonitrile  (25): pale yellow oil, isolated yield: 90%. ¹H NMR (400 MHz, CDCl₃) δ 7.63 (d, J = 8.3 Hz, 2H), 7.55 (d, J = 8.2 Hz, 2H), 7.24-7.12 (m, 6H), 6.77 (t, J = 7.3 Hz, 1H), 6.54 (d, J = 7.9 Hz, 2H), 5.52 (s, 1H), 4.26 (s, 1H), 2.37 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 148.55, 146.89, 139.08, 138.00, 132.66, 129.87, 129.34, 128.01, 127.62, 118.92, 118.36, 113.64, 111.16, 62.76, 21.18. HRMS (MALDI-TOF) calculated for C₂₁H₁₈N₂ [M+H]⁺: 299.1548, found: 299.1545.

4-((4-Methoxyphenyl)(phenylamino)methyl)benzonitrile  (26): white solid, isolated yield: 98%. ¹H NMR (400 MHz, CDCl₃) δ 7.58 (d, J = 8.2 Hz, 2H), 7.49 (d, J = 8.1 Hz, 2H), 7.17 (d, J = 8.5 Hz, 2H), 7.11 (t, J = 7.8 Hz, 2H), 6.85 (d, J = 8.5 Hz, 2H), 6.71 (t, J = 7.4 Hz, 1H), 6.49 (d, J = 7.9 Hz, 2H), 5.46 (s, 1H), 4.19 (s, 1H), 3.76 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 159.40, 148.63, 146.87, 134.14, 132.64, 129.31, 128.89, 127.98, 118.91, 118.30, 114.51, 113.61, 111.09, 62.34, 55.38. HRMS (MALDI-TOF) calculated for C₂₁H₁₈N2O [M-H]⁺: 313.1341, found: 313.1337.

4-((4-Chlorophenyl)(phenylamino)methyl)benzonitrile  (27): white solid, isolated yield: 82%. ¹H NMR (400 MHz, CDCl₃) δ 7.61 (d, J = 8.3 Hz, 2H), 7.47 (d, J = 8.2 Hz, 2H), 7.31 (d, J = 8.5 Hz, 2H), 7.23 (d, J = 8.4 Hz, 2H), 7.17-7.09 (m, 2H), 6.74 (t, J = 7.4 Hz, 1H), 6.50 (d, J = 7.7 Hz, 2H), 5.50 (s, 1H), 4.17 (s, 1H). ¹³C NMR (100 MHz, CDCl₃) δ 147.69, 146.50, 140.22, 133.96, 132.75, 129.33, 129.31, 128.94, 128.06, 118.64, 113.67, 111.55, 62.29. HRMS (MALDI-TOF) calculated for C₂₀H₁₅ClN₂ [M+H]⁺: 319.1002, found: 319.0998.

4-(Naphthalen-2-yl(phenylamino)methyl)benzonitrile (28): white solid, isolated yield: 91%. ¹H NMR (400 MHz, CDCl₃) δ 7.86-7.74 (m, 3H), 7.73 (s, 1H), 7.59 (d, J = 8.3 Hz, 2H), 7.53 (d, J = 8.3 Hz, 2H), 7.47 (dd, J = 6.2, 3.3 Hz, 2H), 7.38 (dd, J = 8.5, 1.5 Hz, 1H), 7.13 (t, J = 7.9 Hz, 2H), 6.74 (t, J = 7.3 Hz, 1H), 6.54 (d, J = 7.9 Hz, 2H), 5.67 (s, 1H), 4.30 (s, 1H). ¹³C NMR (100 MHz, CDCl₃) δ 148.14, 146.88, 139.16, 133.48, 133.06, 132.72, 129.39, 129.19, 128.26, 128.10, 127.82, 126.67, 126.60 126.52, 125.42, 118.84, 118.51, 113.74, 111.37, 63.14. HRMS (MALDI-TOF) calculated for C₂₄H₁₈N₂ [M-H]⁺: 333.1392, found: 333.1388.

4-(((4-Fluorophenyl)amino)(phenyl)methyl)benzonitrile  (29): pale yellow oil, isolated yield: 93%. ¹H NMR (400 MHz, CDCl₃) δ 7.60 (d, J = 8.2 Hz, 2H), 7.50 (d, J = 8.2 Hz, 2H), 7.36-7.27 (m, 5H), 6.81 (t, J = 8.7 Hz, 2H), 6.49-6.38 (m, 2H), 5.45 (s, 1H), 4.15 (s, 1H). ¹³C NMR (100 MHz, CDCl₃) δ 156.46 (d, J = 237.35 Hz), 148.14, 143.16 (d, J = 2.02 Hz), 141.76, 132.72, 129.23, 128.23, 128.04, 127.61, 118.82, 115.80 (d, J = 23 Hz) 114.51 (d, J = 8.08 Hz), 111.34, 63.52. ¹⁹F NMR (377 MHz, CDCl₃) δ -126.70. HRMS (MALDI-TOF) calculated for C₂₀H₁₅FN₂ [M+H]⁺: 303.1298, found: 303.1292.

4-(((4-Chlorophenyl)amino)(phenyl)methyl)benzonitrile  (30): pale yellow oil, isolated yield: 78%. ¹H NMR (400 MHz, CDCl₃) δ 7.61 (d, J = 8.3 Hz, 2H), 7.48 (d, J = 8.2 Hz, 2H), 7.38-7.22 (m, 5H), 7.06 (d, J = 8.8 Hz, 2H), 6.42 (d, J = 8.8 Hz, 2H), 5.47 (s, 1H), 4.26 (s, 1H). ¹³C NMR (100 MHz, CDCl₃) δ 147.80, 145.33, 141.47, 132.76, 129.28, 129.19, 128.33, 128.05, 127.64, 123.11, 118.77, 114.77, 111.45, 63.03. HRMS (MALDI-TOF) calculated for C₂₀H₁₅ClN₂ [M+Na]⁺: 341.0821, found: 341.0816.

4-(((4-Methoxyphenyl)amino)(phenyl)methyl)benzonitrile (31): pale yellow oil, isolated yield: 99%. ¹H NMR (400 MHz, CDCl₃) δ 7.62 (d, J = 8.3 Hz, 2H), 7.54 (d, J = 8.2 Hz, 2H), 7.35-7.30 (m, 5H), 6.74 (d, J = 8.9 Hz, 2H), 6.48 (d, J = 8.9 Hz, 2H), 5.46 (s, 1H), 4.02 (s, 1H), 3.72 (s, 3H). ¹³C NMR (100 MHz, CDCl₃) δ 152.69, 148.63, 142.17, 141.04, 132.67, 129.16, 128.10. 128.07, 127.64, 118.90, 114.92, 114.88, 111.19, 63.79, 55.80. HRMS (MALDI-TOF) calculated for C₂₁H₁₈N₂O [M]⁺: 314.1419, found: 314.1415.

4-(Phenyl((4-(trifluoromethyl)phenyl)amino)methyl)benzonitrile (32): pale yellow oil, isolated yield: 47%. ¹H NMR (400 MHz, CDCl₃) δ 7.64 (d, J = 8.3 Hz, 2H), 7.49 (d, J = 8.2 Hz, 2H), 7.41-7.29 (m, 5H), 7.27 (dd, J = 8.5, 1.7 Hz, 2H), 6.53 (d, J = 8.5 Hz, 2H), 5.57 (d, J = 4.1 Hz, 1H), 4.54 (d, J = 2.9 Hz, 1H). ¹³C NMR (100 MHz, CDCl₃) δ 149.18, 147.31, 141.07, 132.87, 129.41, 128.53, 128.08, 127.69, 126.76 (q, J = 4.04 Hz), 124.85 (q, J = 270.68 Hz), 120.18 (q, J = 33.33 Hz) 118.70, 112.98, 111.71, 62.63. ¹⁹F NMR (377 MHz, CDCl₃) δ -61.22. HRMS (MALDI-TOF) calculated for C₂₁H₁₅F₃N₂ [M+H]⁺: 353.1266, found: 353.1260.

We initially tested our hypothesis by using benzaldehyde (1) and 1, 4-dicyanobenzene (1, 4-DCB, 2) as substrates, fac-Ir(ppy)₃ as photocatalyst and diisopropylethylamine (DIPEA) as the stoichiometric reductant in CH₃CN. To our delight, the desired benzhydrol was formed in 37% yield under blue light irradiation for 12 h (Table 1, entry 1). This encouraging result prompted us to optimize the efficiency of this reaction (Table 1). First, we carried out a solvent screen. When the reaction was performed in DMSO, the yield was dramatically enhanced to 82% (Table 1, entry 2). Other solvents such as acetone, DMF, 1, 4-dioxane, DCM, DCE and MeOH showed lower efficiency than CH₃CN (Table 1, entries 3-8). Replacing the iridium catalyst and electron donor with [Ru(bpy)₃]Cl₂ and Hantzsch ester, respectively, led to a sharp decrease in the yield (Table 1, entries 9 and 10). Triethylamine gave a similar yield to DIPEA (Table 1, entry 11), and increasing the loading of benzaldehyde and DIPEA did not further improve the yields of desired product (Table 1, entries 12 and 13). No product was obtained when DIPEA, visible light or photocatalyst were omitted, indicating that these three components were vital to the performance of the reaction (Table 1, entries 14-16).

With the optimized conditions in hand, we applied this visible-light-catalyzed cross-coupling reaction to a range of molecules containing a C=X bond (X = O, N) and electron-deficient arenes to examine the scope. A variety of aryl nitriles afforded the corresponding cross-coupled products when benzaldehyde was used as the reaction partner, as shown in Scheme 2. A range of substituents, such as methyl, sulfuryl and ester groups, were tolerated well in this reaction (4-7). Aza-aromatic substrates, including 1H-pyrrolo[2, 3-b]-pyridine-4-carbonitrile, isonicotinonitrile, 2, 6-dimethyl-isonicotinonitrile and isoquinoline-1-carbonitrile, also worked well affording the corresponding products in yields 82%-99% (8-11).

We then explored the scope of the substrates containing the C=O double bond (aldehydes and ketones) reacting with 1, 4-DCB. The desired products were obtained in good to excellent yields. The results show that aldehydes with an electron-donating group had higher activity than those with electron-withdrawing groups (12, 13, 16). Thiofuran and naphthalene were both compatible to give moderate yields (14, 15). In sharp contrast to the aryl aldehyde, alkyl aldehydes were not reactive at all. Interestingly, ketones were found to be excellent reaction partners in this strategy, and showed higher reactivity than aldehydes (17). Under the optimized conditions, various substituted acetophenones and indanone afforded the desired products in 76%-87% yield (18-22). An acetophenone containing a cyclopropane group was also converted into the desired compound with preservation of three-membered ring (23).

Encouraged by the above results, we wanted to expand the scope of the new system by investigating the reactions of compounds containing a C=N bond. To our delight, a range of aryl imines were active in this reaction, as shown in Scheme 4. Numerous substitutions, including hydrogen, methyl, methoxy and chlorine all reacted well to give the desired products in 82%-98% yield (24-27). A naphthyl group was also tolerated to give 91% yield (28). When the para-proton of the aryl ring in R₄ position was replaced with an electron-poor group, such as fluorine, chlorine or trifluoromethyl, the reactions gave moderate yields (29, 30, 32). The methoxy substituent at the same position gave an excellent yield of the desired product (31).

To further investigate the reaction process, radical trapping experiments were performed. When two equiv. of TEMPO were added into the template reaction, the yield of the desired product decreased dramatically from 82% to 19%. This suggests the presence of a radical pathway in the reaction mechanism. Further details about the mechanism were determined by spectroscopic investigation. Quenching the excited iridium catalyst from the reactions involving 1, 4-DCB, benzaldehyde and DIPEA (Fig. 1) demonstrated that 1, 4-DCB was the only species to strongly interact with the excited Ir(ppy)₃ [35-38]. However, the excited Ir(ppy)₃ was not able to either reduce the aldehyde or oxidize the DIPEA because of the unfavorable redox potentials (reductive potentials for ^*Ir(ppy)₃, aldehyde and 1, 4-DCB are -1.73, -1.93 and -1.61V, respectively vs SCE; oxidative potentials for Ir(ppy)₃^* and DIPEA are 0.31 and 0.71 V, respectively vs SCE) [35, 38, 39]. We therefore believe that this reaction begins with an interaction between Ir(ppy)₃^* and 1, 4-DCB.

Based on the above results and from previous reports [4, 5], we proposed a plausible mechanism for this transformation (Scheme 5). Visible-light irradiation promotes the photosensitizer fac-Ir(ppy)₃ to its excited state, a long-lived triplet state, which is oxidatively quenched by 1, 4-DCB to afford the corresponding aryl radical anion B and oxidized iridium complex [Ir^Ⅳ(ppy)₃]⁺ (E_1/2^ox = 0.77 V). The generated Ir^Ⅳ abstracts one electron from DIPEA to yield a DIPEA radical cation and regenerate the ground state Ir(ppy)₃. Under the activation of this nitrogen radical cation, the C=O double bond is reduced by excited photocatalyst to afford the key radical intermediate A, which subsequently couples with the aryl radical anion to furnish the desired product.

In summary, we have successfully achieved the reductive radical-radical cross coupling of double bonds (C=O and C=N) with electron-deficient aryl nitriles under mild reaction conditions. With a polarity inversion strategy induced by visible-light catalysis, various aryl substituted alcohols and amines have been constructed without involving air-or water-sensitive reagents. Broad substrate scope, high reaction yields and facile reaction conditions make this method a promising new approach for these important motifs. Further investigations into visible-light-induced polarity inversions are underway in our laboratory.

Acknowledgments

We thank Alison McGonagle, PhD, from Liwen Bianji, Edanz Editing China (www.liwenbianji.cn/ac), for editing the English text of a draft of this manuscript.