Photo-induced reductive cross-coupling of aldehydes, ketones and imines with electron-deficient arenes to construct aryl substituted alcohols and amines

Article abstract of DOI:10.1016/S1872-2067(17)62896-1

Umpolung reactions of C=X bonds (X = O, N) are valuable ways of constructing new C–C bonds, which are sometimes difficult to be constructed using traditional synthetic pathways. Classical polarity inversion of C=X bonds (X = O, N) usually requires air or moisture-sensitive and strong reducing agents, which limit the feasibility of substrate scope. Herein we describe a photo-induced reductive cross-coupling reaction of aldehydes, ketones and imines with electron-deficient arenes (aromatic nitriles) using fac-Ir(ppy)₃ as a photocatalyst and diisopropylethylamine (DIPEA) as a terminal reductant under visible light irradiation. Mild conditions and high yields mean that this new polarity inversion strategy can be used with aryl-substituted alcohols and amines. Spectroscopic studies and control experiments have demonstrated the oxidative quenching of Ir(ppy)₃^* by electron-deficient arenes involved in the key step for the C–C bond formation.

Full text of DOI:10.1016/S1872-2067(17)62896-1

Chinese Journal of Catalysis 39 (2018) 487–494
a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m
j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / c h n j c
Article (Special Issue of Photocatalysis for Solar Fuels)
Photo‐induced reductive cross‐coupling of aldehydes, ketones and
imines with electron‐deficient arenes to construct aryl substituted
alcohols and amines
Zan Liu a,b, Xiaolei Nan a,b, Tao Lei a,b, Chao Zhou a,b, Yang Wang a,b, Wenqiang Liu a,b, Bin Chen a,b,
Chenho Tung a,b, Lizhu Wu a,b,
*
a Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences,
Beijing 100190, China
b University of Chinese Academy of Sciences, Beijing 100049, China
A R T I C L E I N F O
A B S T R A C T
Article history:
Umpolung reactions of C=X bonds (X = O, N) are valuable ways of constructing new C–C bonds,
which are sometimes difficult to be constructed using traditional synthetic pathways. Classical po‐
larity inversion of C=X bonds (X = O, N) usually requires air or moisture‐sensitive and strong reduc‐
ing agents, which limit the feasibility of substrate scope. Herein we describe a photo‐induced reduc‐
tive cross‐coupling reaction of aldehydes, ketones and imines with electron‐deficient arenes (aro‐
matic nitriles) using fac‐Ir(ppy)3 as a photocatalyst and diisopropylethylamine (DIPEA) as a termi‐
nal reductant under visible light irradiation. Mild conditions and high yields mean that this new
polarity inversion strategy can be used with aryl‐substituted alcohols and amines. Spectroscopic
Received 17 September 2017
Accepted 26 October 2017
Published 5 March 2018
Keywords:
Aryl substituted alcohols and amines
Radical‐radical cross coupling
Polarity reversal
Photocatalysis
Arylation
*
studies and control experiments have demonstrated the oxidative quenching of Ir(ppy)3 by elec‐
tron‐deficient arenes involved in the key step for the C–C bond formation.
© 2018, Dalian Institute of Chemical Physics, Chinese Academy of Sciences.
Published by Elsevier B.V. All rights reserved.
1. Introduction
range of substrates are compatible [24,25], greatly limiting
their subsequent transformation. In contrast to using tradition‐
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] com‐
plexes, organic dyes [18–21] and semiconductors [22,23] have
been successfully used in single electron transfer (SET) to acti‐
vate 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
al 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 cou‐
pling of ketones and amines with activated C–H bonds, includ‐
ing benzylic ethers with the β‐position of enamines generated
in situ. More recently, Rueping et al. [30,31] realized the dimer‐
* Corresponding author. Tel/Fax: +86‐10‐82543580; E‐mail: lzwu@mail.ipc.ac.cn
This work was supported by the Ministry of Science and Technology of China (2013CB834804, 2014CB239402), the National Natural Science Foun‐
dation of China (21390404, 91427303), and the Strategic Priority Research Program of the Chinese Academy of Science (XDB17030400).
DOI: 10.1016/S1872‐2067(17)62896‐1 | http://www.sciencedirect.com/science/journal/18722067 | Chin. J. Catal., Vol. 39, No. 3, March 2018

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Zan Liu et al. / Chinese Journal of Catalysis 39 (2018) 487–494
ization 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] ex‐
panded 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 po‐
larity 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 gener‐
ally 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.
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 diphe‐
nylacetonitrile (23.2 mg) was added as an internal standard
and the yield (19%) was detected by 1H NMR.
2.4. General procedure for the polarity inversion/arylation
process
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.
2. Experimental
2.1. General methods
1H NMR spectra were recorded using a Bruker Avance DPX
400 MHz instrument with tetramethylsilane (TMS) as the in‐
ternal 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. Com‐
mercially 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.
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.
2.2. General procedure for the preparation of imines
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.
4‐(Hydroxy(phenyl)methyl)‐2‐methylbenzonitrile
and
4‐(hydroxyl(phenyl)methyl)‐3‐methylbenzonitrile (4): color‐
less 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.
2.3. General procedure for radical trapping experiments
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.
Scheme 1. Visible light catalyzed umpolung reactions of C=X (X = O, N)
with electron‐deficient arenes.

Zan Liu et al. / Chinese Journal of Catalysis 39 (2018) 487–494
489
Methyl 4‐(hydroxy(phenyl)methyl)benzoate (6): colorless
238.0871.
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.
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.
5‐(Hydroxy(phenyl)methyl)isobenzofuran‐1(3H)‐one (7):
1
white solid, isolated yield: 42%. H NMR (400 MHz, CDCl3) δ
4‐(Hydroxy(naphthalen‐2‐yl)methyl)benzonitrile
(15):
1
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.
white solid, isolated yield: 62%. H 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) cal‐
culated 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.
Phenyl(1H‐pyrrolo[2,3‐b]pyridin‐4‐yl)methanol (8): yellow
1
oil, isolated yield: 82%. H 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.
4‐(1‐(4‐Ethylphenyl)‐1‐hydroxyethyl)benzonitrile
(19):
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.
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.
(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). 13
C
4‐(1‐Hydroxy‐2,3‐dihydro‐1H‐inden‐1‐yl)benzonitrile (20):
colorless oil, isolated yield: 81%. H NMR (400 MHz, CDCl3) δ
1
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.
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.
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‐(1‐(4‐Chlorophenyl)‐1‐hydroxyethyl)benzonitrile (21):
1
white solid, isolated yield: 76%. H 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‐((4‐Chlorophenyl)(hydroxy)methyl)benzonitrile
(12):
1
white solid, isolated yield: 55%. H 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) cal‐
culated for C14H10ClNO [M‐H]+: 242.0373, found: 242.0377.
4‐(1‐Hydroxy‐1‐(4‐methoxyphenyl)ethyl)benzonitrile (22):
1
colorless oil, isolated yield: 76%. H 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‐(Hydroxy(4‐methoxyphenyl)methyl)benzonitrile
(13):
1
white solid, isolated yield: 83%. H 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:
4‐(Cyclopropyl(hydroxy)(phenyl)methyl)benzonitrile (23):
white solid, isolated yield: 67%. 1H NMR (400 MHz, CDCl3) δ

490
Zan Liu et al. / Chinese Journal of Catalysis 39 (2018) 487–494
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 yel‐
low 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.
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
1
(30): pale yellow oil, isolated yield: 78%. H 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
1
(31): pale yellow oil, isolated yield: 99%. H 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)benzo
1
nitrile (32): pale yellow oil, isolated yield: 47%. H 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.
3. Results and discussion
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 de‐
light, the desired benzhydrol was formed in 37% yield under
blue light irradiation for 12 h (Table 1, entry 1). This encour‐
aging result prompted us to optimize the efficiency of this reac‐
tion (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 omit‐
ted, indicating that these three components were vital to the
4‐(((4‐Fluorophenyl)amino)(phenyl)methyl)benzonitrile
1
(29): pale yellow oil, isolated yield: 93%. H 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),

Zan Liu et al. / Chinese Journal of Catalysis 39 (2018) 487–494
491
strates, including 1H‐pyrrolo[2,3‐b]‐pyridine‐4‐carbonitrile,
isonicotinonitrile, 2,6‐dimethyl‐ isonicotinonitrile and isoquin‐
oline‐1‐carbonitrile, also worked well affording the corre‐
sponding products in yields 82%–99% (8–11).
Table 1
Optimization of reaction conditions. a
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 excel‐
lent yields. The results show that aldehydes with an elec‐
tron‐donating group had higher activity than those with elec‐
tron‐withdrawing groups (12, 13, 16). Thiofuran and naph‐
thalene 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 con‐
taining a cyclopropane group was also converted into the de‐
sired 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 com‐
pounds containing a C=N bond. To our delight, a range of aryl
imines were active in this reaction, as shown in Scheme 4. Nu‐
merous 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 moder‐
ate 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 prod‐
Entry
1
2
3
4
5
6
7
8
Photocatalyst
fac‐Ir(ppy)3
fac‐Ir(ppy)3
fac‐Ir(ppy)3
fac‐Ir(ppy)3
fac‐Ir(ppy)3
fac‐Ir(ppy)3
fac‐Ir(ppy)3
fac‐Ir(ppy)3
[Ru(bpy)3]Cl2
fac‐Ir(ppy)3
fac‐Ir(ppy)3
fac‐Ir(ppy)3
fac‐Ir(ppy)3
fac‐Ir(ppy)3
fac‐Ir(ppy)3
None
Solvent
CH3CN
DMSO
DMF
Acetone
1,4‐Dioxane
DCM
Yield b (%)
37
82
<5
13
<5
<5
6
DCE
MeOH
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
<5
0
9
10 c
11 d
12 e
13 f
14 g
15 h
16
29
80
82
82
0
0
0
a Reaction conditions: Benzaldehyde (0.3 mmol), 1,4‐DCB (0.2 mmol),
DIPEA (0.3 mmol), fac‐Ir(ppy)3 (2 mol%) blue LEDs irradiated for 12 h
under an argon atmosphere. b Detected by 1H NMR analysis with di‐
phenylacetonitrile as the internal standard. c Hantzsch ester (HE, 0.3
mmol) as reductant. d Et3N (0.3 mmol) as reductant. e Benzaldehyde (0.4
mmol). f DIPEA (0.4 mmol). g No DIPEA. h No light.
performance of the reaction (Table 1, entries 14–16).
With the optimized conditions in hand, we applied this visi‐
ble‐light‐catalyzed cross‐coupling reaction to a range of mole‐
cules 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 sub‐
CN
OH
R2
O
2 moI % fac-Ir(ppy)3
R2
+
DIPEA, DMSO
CN
h , Ar, rt, 12 h
R1
R1
CN
OH
OH
OH
S
CN
O
CN
Cl
CN
12, 55%
13, 83%
14, 68%
OH
OH
OH
O2N
CN
CN
CN
CN
16, nr
15, 62%
17, nr
HO
OH
CN
HO
CN
18, 82%
HO
19, 87%
20, 81%
HO
HO
MeO
CN
Cl
CN
CN
23, 67%
21, 76%
22, 76%
Scheme 2. Screening electron‐deficient aryl nitrile substrates.
Scheme 3. Screening aldehyde and ketone substrates.

492
Zan Liu et al. / Chinese Journal of Catalysis 39 (2018) 487–494
troscopic investigation. Quenching the excited iridium catalyst
R4
R4
CN
CN
N
HN
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 poten‐
2 mol % fac-Ir(ppy)3
+
DIPEA, DMSO
h , Ar, rt,12 h
R3
R3
CN
HN
HN
HN
*
tials (reductive potentials for Ir(ppy)3, aldehyde and 1,4‐DCB
are –1.73, –1.93 and –1.61V, respectively vs SCE; oxidative po‐
tentials for Ir(ppy)3 and DIPEA are 0.31 and 0.71 V, respec‐
CN
CN
O
CN
24, 83%
25, 90%
26, 98%
*
F
tively vs SCE) [35,38,39]. We therefore believe that this reac‐
tion 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 photosensi‐
tizer fac‐Ir(ppy)3 to its excited state, a long‐lived triplet state,
which is oxidatively quenched by 1,4‐DCB to afford the corre‐
sponding aryl radical anion B and oxidized iridium complex
[IrIV(ppy)3]+ (E1/2ox = 0.77 V). The generated IrIV abstracts one
electron from DIPEA to yield a DIPEA radical cation and regen‐
erate 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 fur‐
nish the desired product.
HN
HN
HN
Cl
CN
CN
CN
27, 82%
28, 91%
29, 93%
Cl
O
CF3
HN
HN
HN
CN
CN
CN
30, 78%
31, 99%
32, 47%
Scheme 4. Screening imine substrates.
uct decreased dramatically from 82% to 19%. This suggests the
presence of a radical pathway in the reaction mechanism. Fur‐
ther details about the mechanism were determined by spec‐
(a)
(b)
0 mol/L
0 mol/L
103 mol/L
103 mol/L
400
500
600
700
800
400
500
600
700
800
Wavelength (nm)
Wavelength (nm)
(d)
(c)
0 mol/L
103 mol/L
Eox
0.0
0.2
0.4
0.6
0.8
1.0
400
500
600
700
800
Wavelength (nm)
Voltage (V) vs SCE
Fig. 1. Luminescence spectra of Ir(ppy)3 as a function of concentration of 1,4‐DCB (a), benzaldehyde (b) and DIPEA (c). [Ir(ppy)3] = 1 × 10‒5 mol/L;
solvent, DMSO; excitation wavelength, 400 nm. (d) CV spectra of DIPEA. [DIPEA] = 10–2 mol/L.

Zan Liu et al. / Chinese Journal of Catalysis 39 (2018) 487–494
493
laboratory.
DIPEA
O
Acknowledgments
1
Ir(ppy)3
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.
h
OH
Ir(ppy)3
+
References
A
Ir(ppy)3
OH
[1] D. A. Nicewicz, D. W. C. MacMillan, Science, 2008, 322, 77–80.
[2] M. A. Ischay, M. E. Anzovino, J. Du, T. P. Yoon, J. Am. Chem. Soc.,
2008, 130, 12886–12887.
DIPEA
DIPEA
or
or
Ni-Pr
DIPEA
[3] J. M. R. Narayanam, J. W. Tucker, C. R. J. Stephenson, J. Am. Chem.
Soc., 2009, 131, 8756–8757.
[4] D. C. Fabry, M. A. Ronge, J. Zoller, M. Rueping, Angew. Chem. Int. Ed.,
2015, 54, 2801–2805.
+
CN
Ir(ppy)3
3
NC
CN
Ir(ppy)3
B
[5] D. C. Fabry, J. Zoller, S. Raja, M. Rueping, Angew. Chem. Int. Ed.,
2014, 53, 10228–10231.
[6] J. Du, T. P. Yoon, J. Am. Chem. Soc., 2009, 131, 14604–14605.
[7] M. A. Ischay, Z. Lu, T. P. Yoon, J. Am. Chem. Soc., 2010, 132,
8572–8574.
h
Ir(ppy)3
NC
CN
[8] C. J. Wallentin, J. D. Nguyen, P. Finkbeiner, C. R. J. Stephenson, J. Am.
Chem. Soc., 2012, 134, 8875–8884.
[9] G. L. Lackner, K. W. Quasdorf, L. E. Overman, J. Am. Chem. Soc.,
2013, 135, 15342–15345.
2
Scheme 5. Possible reaction mechanism.
[10] D. Kalyani, K. B. McMurtrey, S. R. Neufeldt, M. S. Sanford, J. Am.
Chem. Soc., 2011, 133, 18566–18569.
4. Conclusions
[11] X. Q. Hu, J. R. Chen, Q. Q. Zhao, Q. Wei, W. J. Xiao, X. T. Qi, Y. Lan,
Nat. Commun., 2016, 7, 11188.
[12] J. D. Cuthbertson, D. W. C. MacMillan, Nature, 2015, 519, 74–77.
[13] C. P. Johnston, R. T. Smith, S. Allmendinger, D. W. C. MacMillan,
Nature, 2016, 536, 322–325.
[14] X. Q. Huang, R. D. Webster, K. Harms, E. Meggers, J. Am. Chem. Soc.,
2016, 138, 12636–12642.
[15] J. D. Nguyen, E. M. D'Amato, J. M. R. Narayanam, C. R. J. Stephenson,
Nat. Chem., 2012, 4, 854–859.
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 condi‐
tions. 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 re‐
agents. Broad substrate scope, high reaction yields and facile
reaction conditions make this method a promising new ap‐
proach for these important motifs. Further investigations into
visible‐light‐induced polarity inversions are underway in our
[16] G. J. Choi, Q. L. Zhu, D. C. Miller, C. J. Gu, R. R. Knowles, Nature,
2016, 539, 268–271.
Graphical Abstract
Chin. J. Catal., 2018, 39: 487–494 doi: 10.1016/S1872‐2067(17)62896‐1
Photo‐induced reductive cross‐coupling of aldehydes, ketones
and imines with electron‐deficient arenes to construct aryl
substituted alcohols and amines
Zan Liu, Xiaolei Nan, Tao Lei, Chao Zhou, Yang Wang,
Wenqiang Liu, Bin Chen, Chenho Tung, Lizhu Wu *
Technical Institute of Physics and Chemistry, Chinese Academy of
Sciences; University of Chinese Academy of Sciences
Aryl‐substituted alcohols and amines have been efficiently con‐
structed by reductive radical‐radical cross‐coupling between al‐
dehydes, ketones and imines with electron‐deficient arenes under
visible‐light catalysis. The strategy of polarity inversion of the C=X
bond (X = O, N) avoids the use of air‐ and water‐sensitive reagents,
tolerates various functional groups and produces the desired
products in yields up to 99% at room temperature.

494
Zan Liu et al. / Chinese Journal of Catalysis 39 (2018) 487–494
[17] A. J. Musacchio, B. C. Lainhart, X. Zhang, S. G. Naguib, R. R. Knowles,
T. C. Sherwood, Science, 2017, 355, 727–730.
[18] Q. Y. Meng, J. J. Zhong, Q. Liu, X. W. Gao, H. H. Zhang, T. Lei, Z. J. Li, K.
Feng, B. Chen, C. H. Tung, L. Z. Wu, J. Am. Chem. Soc., 2013, 135,
19052–19055.
2015, 137, 8404–8407.
[29] F. R. Petronijević, M. Nappi, D. W. C. MacMillan, J. Am. Chem. Soc.,
2013, 135, 18323–18326.
[30] M. Nakajima, E. Fava, S. Loescher, Z. Jiang, M. Rueping, Angew.
Chem. Int. Ed., 2015, 54, 8828–8832.
[19] G. T. Zhang, X. Hu, C. W. Chiang, H. Yi, P. K. Pei, A. K. Singh, A. W.
Lei, J. Am. Chem. Soc., 2016, 138, 12037–12040.
[20] J. Schwarz, B. Konig, Green Chem., 2016, 18, 4743–4749.
[21] X. Y Yu, F Zhou, J. R. Chen, W. J. Xiao, Acta Chim. Sin., 2017, 75,
86–91.
[31] E. Fava, A. Millet, M. Nakajima, S. Loescher, M. Rueping, Angew.
Chem. Int. Ed., 2016, 55, 6776–6779.
[32] W. Ding, L. Q. Lu, J. Liu, D. Liu, H. T. Song, W. J. Xiao, J. Org. Chem.,
2016, 81, 7237–7243.
[33] L. Qi, Y. Y. Chen, Angew. Chem. Int. Ed., 2016, 55, 13312–13315.
[34] K. N. Lee, Z. Lei, M. Y. Ngai, J. Am. Chem. Soc., 2017, 139,
5003–5006.
[22] A. R. Wade, H. R. Pawar, M. V. Biware, R. C. Chikate, Green Chem.,
2015, 17, 3879–3888.
[23] X. J. Lang, J. C. Zhao, X. D. Chen, Angew. Chem. Int. Ed., 2016, 55,
4697–4700.
[35] A. McNally, C. K. Prier, D. W. C. MacMillan, Science, 2011, 334,
1114–1117.
[24] T. Ikeda, S. Yue, C. R. Hutchinson, J. Org. Chem., 1985, 50, 5193–5199.
[25] M. Szostak, D. J. Procter, Angew. Chem. Int. Ed., 2012, 51,
9238–9256.
[26] L. J. Rono, H. G. Yayla, D. Y. Wang, M. F. Armstrong, R. R. Knowles, J.
Am. Chem. Soc., 2013, 135, 17735–17738.
[27] K. T. Tarantino, P. Liu, R. R. Knowles, J. Am. Chem. Soc., 2013, 135,
10022–10025.
[28] J. L. Jeffrey, F. R. Petronijević, D. W. C. MacMillan, J. Am. Chem. Soc.,
[36] M. T. Pirnot, D. A. Rankic, D. B. C. Martin, D. W. C. MacMillan, Sci‐
ence, 2013, 339, 1593–1596.
[37] K. Qvortrup, D. A. Rankic, D. W. C. MacMillan, J. Am. Chem. Soc.,
2014, 136, 626–629.
[38] H. G. Roth, N. A. Romero, D. A. Nicewicz, Synlett, 2016, 27,
714–723.
[39] C. K. Prier, D. A. Rankic, D. W. C. MacMillan, Chem. Rev., 2013, 113,
5322–5363.
可见光催化醛、酮或亚胺与缺电子芳烃还原偶联构筑芳基取代醇和胺
刘 赞a,b, 南小磊a,b, 雷 涛a,b, 周 超a,b, 王 阳a,b, 刘文强a,b, 陈 彬a,b, 佟振合a,b, 吴骊珠a,b,*
a中国科学院理化技术研究所, 光化学转换与功能材料重点实验室, 北京100190
b中国科学院大学, 北京100049
摘要: 通过C=X (X=O, N)双键极性翻转构筑碳-碳键是有机化学反应的重要合成策略. 传统C=X (X=O, N)双键的极性翻转
往往需要苛刻的反应条件和对水或空气敏感的强还原剂辅助, 导致其适用范围受限. 近年来, 可见光催化反应以其独特高
效的单电子转移特性, 在室温条件下实现了这一类贫电子官能团向亲核性中间体的高效转化. 该策略已经拓展C=X (X=O,
N)双键自身或与烷基链的偶联, 从而得到烷基取代的醇和胺类化合物. 本文利用可见光催化反应使C=X (X=O, N)双键极
性翻转与芳香化合物的直接偶联, 高效温和地合成芳基取代的醇和胺. 反应无需强还原剂, 底物适用范围广. 该方法是对
可见光催化C=X (X=O, N)双键极性翻转的重要补充, 具有潜在的应用价值.
本文以苯甲醛和1,4-二氰基苯为底物, fac-Ir(ppy)3为光敏剂, 二异丙基乙胺为终端还原剂, DMSO为溶剂, 蓝光照射12 h
能够以82%的收率实现模板反应. 其它光敏剂如[Ru(bpy)3]Cl2则不能催化该反应. 溶剂效应指出, 丙酮、乙腈可以得到低于
40%的收率, 甲醇、二氯甲烷、DMF等溶剂不适用该反应体系. 控制实验证实, 光敏剂、二异丙基乙胺和光照三个反应组
分缺一不可. 底物拓展发现, 不同取代基的芳基腈类化合物包括烷基取代、砜基和酯基取代甚至杂芳环取代都能很好地适
用于该体系, 芳基醛、酮以及亚胺作为反应的另一组分亦能高效参与该还原偶联反应.
自由基捕获实验证实反应过程中涉及自由基历程. 光谱淬灭实验表明, 芳香腈是唯一有效淬灭激发态fac-Ir(ppy)3发光
的物种. 进一步结合底物的氧化还原电位, 证实芳香腈能被激发态的光敏剂fac-Ir(ppy)3还原, 但二异丙基乙胺和芳香醛、酮
不能与激发态光敏剂发生作用, 催化反应经历光敏剂的氧化淬灭路径. 首先, 光敏剂受光激发到达激发态, 与芳基腈发生
单电子转移. 随后, 二异丙基乙胺促使失去电子的铱配合物还原再生, 得到相应氮自由基阳离子. 该氮自由基阳离子活化
反应体系中的C=X (X=O, N)双键, 使其从激发态铱物种得到电子形成苄位自由基, 进而与得到电子的芳基氰偶联得到最终
产物.
关键词: 芳基取代的醇和胺; 还原偶联; 极性翻转; 光催化; 芳基化
收稿日期: 2017-09-17. 接受日期: 2017-10-26. 出版日期: 2018-03-05.
*通讯联系人. 电话/传真: (010)82543580; 电子邮箱: lzwu@mail.ipc.ac.cn
基金来源: 国家科技部基金(2013CB834804, 2014CB239402); 国家自然科学基金(21390404, 91427303); 中国科学院战略先导研
究项目基金(XDB17030400).
本文的英文电子版由Elsevier出版社在ScienceDirect上出版(http://www.sciencedirect.com/science/journal/18722067).