Visible-Light-Induced Decarboxylative Cyclization/Hydrogenation Cascade Reaction to Access Phenanthridin-6-yl(aryl)methanol by an Electron Donor-Acceptor Complex

Article abstract of DOI:10.1021/acs.joc.0c01916

A novel and efficient visible-light-induced decarboxylative cyclization/hydrogenation cascade reaction of α-oxocarboxylic acids and 2-isocyanobiaryls has been developed. Without the need of any external photosensitizer, oxidant, and reductant, this method offers a mild and green approach for the synthesis of diverse alcohols in moderate to good yields. A mechanism indicated that an electron donor-acceptor complex-driven decarboxylation, radical addition/cyclization, and in situ photochemical reduction of ketones to alcohols could be involved in the reaction.

Full text of DOI:10.1021/acs.joc.0c01916

pubs.acs.org/joc
Article
Visible-Light-Induced Decarboxylative Cyclization/Hydrogenation
Cascade Reaction to Access Phenanthridin-6-yl(aryl)methanol by an
Electron Donor−Acceptor Complex
Wei Shi, Fang Ma, Pinhua Li, Lei Wang,* and Tao Miao*
Cite This: https://dx.doi.org/10.1021/acs.joc.0c01916
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: A novel and efficient visible-light-induced decar-
boxylative cyclization/hydrogenation cascade reaction of α-
oxocarboxylic acids and 2-isocyanobiaryls has been developed.
Without the need of any external photosensitizer, oxidant, and
reductant, this method offers a mild and green approach for the
synthesis of diverse alcohols in moderate to good yields. A
mechanism indicated that an electron donor−acceptor complex-
driven decarboxylation, radical addition/cyclization, and in situ photochemical reduction of ketones to alcohols could be involved in
the reaction.
Scheme 1. (a) Ag-Catalyzed Oxidative Radical
Decarboxylation/Cyclization of α-Oxocarboxylates and
Isocyanides for the Synthesis of 6-Acyl Phenanthridines; (b)
Electron Donor−Acceptor (EDA) Driven Three-
Component Reactions of Isocyanides, Alkynes, and Sulfinic
Acids; (c) Decarboxylation/Hydrogenation Cascade
Reaction for the Synthesis of Phenanthridin-6-
yl(aryl)methanol
INTRODUCTION
■
α-Oxocarboxylic acids are stable and readily available, and the
carboxyl group is a latent activating group, which can be easily
removed in organic synthesis. Therefore, α-oxocarboxylic acids
have often been employed as acyl synthons by decarboxylative
transformations in recent decades.1 For example, Pd-, Cu-, and
Rh-catalyzed decarboxylative cross-couplings, in which metal-
mediated decarboxylation affords acyl anion equivalents, are an
attractive and useful strategy for the synthesis of diaryl ketones
with aryl halides, arylboronic acids, and C−H moieties.2 In
2014, the Lei group demonstrated a novel approach of the
silver-catalyzed radical decarboxylation for the synthesis of 6-
acyl phenanthridines from α-oxocarboxylates and isocyanides
(Scheme 1a).3 Recently, with the rise of visible-light
photoredox catalysis, photocatalytic decarboxylation of α-
oxocarboxylic acids has provided an effective and environ-
mentally benign avenue to generate acyl radicals for the
preparation of carbonyl compounds.4 Despite these significant
advances, synthetic challenges still remain because these
methods need to employ expensive metal catalysts, strong
oxidants, or additives. Furthermore, compared to extensive
research on preparation of various aryl ketones via acyl anions
or radicals, α-oxocarboxylic acids have not been utilized in the
synthesis of functionalized alcohols, especially by in situ
reduction of aryl ketones. Generally, reduction of carbonyl
compounds serves as an efficient and direct synthetic pathway
to their corresponding alcohols and is typically performed
using complex hydrides as reducing agents or with molecular
hydrogen in combination with precious metal catalysts.5
However, most of these protocols require either a stoichio-
metric amount of hydride reagents or high catalyst loadings
and elevated temperatures, which limit their synthetic
application and functional group compatibilities. Therefore,
developing a green, sustainable, and metal-free decarboxyla-
tion/hydrogenation cascade reaction for the synthesis of
Received: August 7, 2020
https://dx.doi.org/10.1021/acs.joc.0c01916
© XXXX American Chemical Society
J. Org. Chem. XXXX, XXX, XXX−XXX
A

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
diverse alcohols from α-oxocarboxylic acids would be highly
desirable.
visible-light irradiation of 1a and 2a in CH2Cl2 for 10 h under a
N2 atmosphere furnished the corresponding product 3a in 41%
yield, and the structure of 3a was confirmed by the single-
crystal X-ray diffraction (Table 1, entry 1). Further survey of
solvents showed that 1,1,2-trichloroethane shows the best
efficiency as a 78% yield of 3a was provided (Table 1, entry 2).
Other solvents including CHCl3, THF, EtOAc, acetone, and
cyclohexane were less effective and gave the inferior results
(Table 1, entries 3−7). N,N-Dimethylformamide (DMF) and
dimethyl sulfoxide (DMSO) were not suitable solvents and
completely inhibited the reaction (Table 1, entries 8 and 9).
Furthermore, pyridine was an essential parameter in the
formation of 3a, and other bases such as Et3N, 4-
dimethylaminopyridine (DMAP), and K2CO3 instead of
pyridine were to be ineffective in the reaction. Therefore, the
basicity of the base plays a vital role in visible-light-induced
tandem transformation (Table 1, entries 10−12). When the
model reaction was conducted under an air atmosphere,
product 3a was obtained in 45% yield (Table 1, entry 13). In
addition, decreased yields were observed when the amount of
pyridine and phenylglyoxylic acid was reduced (Table 1,
entries 14 and 15). It should be noted that the reaction did not
proceed in the absence of light even when the reaction mixture
was heated to 60 °C for 10 h (Table 1, entries 16 and 17).
Similarly, no product was detected under the irradiation with a
blue LED (450 5 nm) or a green LED (530 5 nm) (Table
1, entries 18 and 19). All these results indicated that this
tandem reaction is a photoinduced process.
EDA complexes resulting from the association of an electron
donor molecule (D) with an electron acceptor molecule (A)
can be excited by visible light to generate radical species for the
synthetically valuable transformations without the need of any
external photocatalyst.6 During the past decades, the search for
more environmentally friendly processes has led chemists
toward the investigation of photochemical reactions driven by
EDA complexes, and great achievements including catalytic
asymmetric alkylation,7 perfluoroalkylation,8 and intramolecu-
lar cyclization9 have been achieved. These promising results
imply that EDA complexes may find more applications in
organic synthesis. Inspired by these recent works and in
continuation of our interest on radical transformation driven
by EDA complexes (Scheme 1a,b),10 herein, we disclose a
visible-light-induced decarboxylative cyclization/hydrogena-
tion cascade for the synthesis of phenanthridin-6-yl(aryl)-
methanol from α-oxocarboxylic acids at room temperature
without any external photosensitizer, oxidant, and reductant
(Scheme 1c).
RESULTS AND DISCUSSION
■
In our initial investigation, we chose phenylglyoxylic acid (1a)
and 2-isocyanobiphenyl (2a) as the model substrates to
identify the optimal reaction conditions, and the results are
summarized in Table 1. At first, we were delighted to find that
With optimized conditions in hand, we next examined the
scope of the α-oxocarboxylic acid component in this
decarboxylative cyclization/hydrogenation cascade reaction.
As described in Scheme 2, a wide range of 2-oxo-2-
phenylacetic acids with different substituents on the phenyl
ring could be applied to react with 2a, providing the desired
products 3a−3n in moderate-to-good yields. The reactions of
substituted 2-oxo-2-phenylacetic acids with an electron-
donating group, such as methyl, ethyl, tert-butyl, methoxy, or
methylthio group, gave the products (3b−3h) in 70−78%
yields. On the other hand, substituted 2-oxo-2-phenylacetic
acids with an electron-withdrawing group including fluoro,
chloro, bromo, or iodo were also good reaction partners and
generated the corresponding products 3i−3m in 50−73%
yields. It was worth mentioning that the reaction showed good
tolerance toward the halogen groups, which provide useful
handles for further transformations through transition-metal-
catalyzed classic cross-coupling reactions. In the case of
disubstituted 2-oxo-2-phenylacetic acid, the reaction under-
went smoothly, affording product 3n in 65% yield.
Heterocyclic α-oxocarboxylic acids, such as 2-oxo-2-(thien-2-
yl)acetic acid, were also investigated, providing the corre-
sponding product 3o in 34% yield.
Subsequently, the substitution effect on both aromatic rings
of biphenyl isocyanide 3 was investigated, and the results are
summarized in Scheme 3. Once again, the reaction was not
sensitive to the electronic nature of the substituents, as
evidenced by the moderate-to-good yields of 3p−3ag. Me-, F-,
and Cl-substituted 2-isocyanobiphenyls on the para position of
the isocyano moiety reacted efficiently with 1, affording the
corresponding products in yields ranging from 61 to 85% (3p−
3s). Furthermore, 2-isocyanobiphenyls containing substituents,
such as Me, OMe, t-Bu, F, Cl, CF3, and SMe on the para
position of the non-isocyanide phenyl ring, are all suitable
substrates for this transformation, and the corresponding
a
Table 1. Optimization of the Reaction Conditions
b
entry
solvent
CH2Cl2
1,1,2-trichloroethane
CHCl3
THF
EtOAc
acetone
cyclohexane
DMF
DMSO
1,1,2-trichloroethane
1,1,2-trichloroethane
1,1,2-trichloroethane
1,1,2-trichloroethane
1,1,2-trichloroethane
1,1,2-trichloroethane
1,1,2-trichloroethane
1,1,2-trichloroethane
1,1,2-trichloroethane
1,1,2-trichloroethane
base
yield (%)
1
2
3
4
5
6
7
8
pyridine
pyridine
pyridine
pyridine
pyridine
pyridine
pyridine
pyridine
pyridine
Et3N
41
78
50
46
65
48
21
0
0
0
0
0
9
10
11
12
13
14
15
16
17
18
19
DMAP
K2CO3
c
pyridine
pyridine
pyridine
pyridine
pyridine
pyridine
pyridine
45
60
55
d
e
f
0
g
0
0
h
i
0
a
Reaction conditions: phenylglyoxylic acid (1a, 0.75 mmol), 2-
isocyanobiphenyl (2a, 0.25 mmol), the base (6.0 equiv), and the
solvent (2 mL) at room temperature under a 3 W LED (420 5 nm)
irradiation for 10 h. Isolated yield based on 2a. Under an air
atmosphere. Phenylglyoxylic acid (1a, 0.50 mmol). Pyridine (4.0
equiv). In the darkness. Under an oil bath to 60 °C in the darkness.
Under a 3 W blue LED (450 5 nm) irradiation. Under a 3 W
green LED (530 5 nm) irradiation.
b
c
d
e
f
g
h
i
B
https://dx.doi.org/10.1021/acs.joc.0c01916
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
a
Scheme 2. Scope of α-Oxocarboxylic Acids
Scheme 3. Scope of Biphenyl Isocyanides and α-
Oxocarboxylic Acids
a
a
[Reaction conditions: α-keto acid (1, 0.75 mmol), biphenyl
isocyanide (2, 0.25 mmol), pyridine (6.0 equiv), and 1,1,2-
trichloroethane (2.0 mL) at room temperature under a 3 W LED
(420 5 nm) irradiation for 10 h; isolated yield based on 2].
a
[Reaction conditions: α-oxocarboxylic acid (1, 0.75 mmol), 2-
isocyanobiphenyl (2a, 0.25 mmol), pyridine (6.0 equiv), and 1,1,2-
trichloroethane (2.0 mL) at room temperature under a 3 W LED
(420 5 nm) irradiation for 10 h; isolated yield based on 2a].
products (3t−3ab) were obtained in moderate-to-good yields.
In the other case, biphenyl isocyanides with two substituted
groups on both aromatic rings were also effective to give the
corresponding 3ac−3ae in 58−71% yields. When the position
of substituents on 2-isocyanobiphenyls was changed, 2 reacted
smoothly with 1a, affording the expected products 3af and 3ag
in 71 and 51% yield, respectively.
Figure 1. Optical absorption spectra of the reaction components.
To gain insights into this photoinduced decarboxylative/
hydrogenation transformation, a series of optical absorption
spectra of phenylglyoxylic acid (1a), 4′-chloro-2-isocyano-1,1′-
biphenyl (2b), pyridine, and a combination of these
components were recorded in 1,1,2-trichloroethane solution.
As depicted in Figure 1, after mixing 1a with 2b, the solution
developed a yellowish color, while its optical absorption
spectrum showed a bathochromic displacement in the visible-
light region, which is diagnostic of an EDA complex (Figure
1). Following Job’s plot method, the stoichiometry of the EDA
complex between 1a and 2b in solution was found to be 1:1
(for details, see Figure S1 in the Supporting Information).
Meanwhile, the association constant KEDA was calculated to be
5.02 M−1 in 1,1,2-trichloroethane using the Benesi−Hilde-
brand equation (Figure S2).11 These results indicate that the
EDA complex is formed between 1a and 2b, and visible-light
irradiation of the transiently generated EDA complex is critical
to afford radical species for reaction development.
thridine (4a) was added to the reaction mixture of 1a and 2c
under optimized reaction conditions, the corresponding
hydrogenated product 3a was obtained in 44% yield, along
with 3x and 4b (Scheme 4a). Moreover, under 3 W LED (420
5 nm) irradiation for 10 h, 6-benzoyl phenanthridine (4a)
can also be hydrogenated to generate 3a in 52% yield in the
presence of 3.0 equiv 1a (Scheme 4b). UV−visible (UV−vis)
measurements revealed that 4a can be excited with light at a
wavelength of 420 nm because of its obvious absorption band
in the wavelength below 480 nm (for details, see Figure S3 in
the Supporting Information). Then, two radical-trapping
experiments were performed. It is found that the formation
of product 3a was completely suppressed in the presence of
TEMPO as a radical scavenger under optimized reaction
conditions, and instead, TEMPO adducts I and II from
benzoyl and hydrogen radicals were detected by electrospray
ionization mass spectrometry (ESI-MS), providing evidence
for the free-radical mechanism (Scheme 4c). On the other
More experiments were conducted to understand the
mechanism of this reaction better. When 6-benzoyl phenan-
C
https://dx.doi.org/10.1021/acs.joc.0c01916
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
Scheme 4. Investigation of the Reaction Mechanism
Scheme 5. Proposed Mechanism for the Formation of 3
CONCLUSIONS
■
In summary, we have developed a visible-light-induced
decarboxylative cyclization/hydrogenation cascade reaction of
α-oxocarboxylic acids and 2-isocyanobiphenyls under external
photosensitizer-, oxidant-, and reductant-free conditions. This
reaction provides a green and facile method for direct synthesis
of diverse alcohols with good functional group compatibility
under mild reaction conditions. Mechanistic investigation
revealed that the decarboxylative cyclizations driven by key
photoactive species of the EDA complex and the subsequent
photochemical reduction of 6-acyl phenanthridine could be
involved in the reaction. Further exploration and applications
of new EDA complexes generated from α-oxocarboxylic acids
and other organic molecules in organic synthesis are still
ongoing in our laboratory.
hand, to further confirm the existence of intermediates for the
hydrogenation process, the reaction of 4a and 1a with TEMPO
was also carried out under optimized conditions. The ESI-MS
analysis of the reaction mixture showed the existence of
hydrogen and important carbon radical addition intermediates
II and III (Scheme 4d). These results suggest that photo-
excitation of 4a could trigger the hydrogen radical abstraction
to form carbon radicals in the hydrogenation step. Deuterium
experiments indicated that H2O and acids are the sources of
hydrogen by using D-1a and D2O (for details, see Figure S7a−
c in the Supporting Information). Furthermore, the inter-
molecular kinetic isotopic effect (KIE) experiment confirmed
that KH/KD for the arene C−H bond was 1.0, indicating that
the cleavage of the arene C−H bond was not the rate-
determining step, and free-radical cyclization was involved in
this transformation (for details, see Figure S7d). A further
control experiment suggested that the photochemical reduc-
tion of ketones to alcohols could be involved in the rate-
determining step, with the starting material in one pot under
optimized conditions (for details, see Figure S7e).
On the bases of these experimental results and previous
reports,6−10 a plausible mechanism is proposed in Scheme 5.
First, an EDA complex was formed between α-oxocarboxylic
acid 1 and 2a in the presence of pyridine. Upon visible-light
irradiation, this EDA complex generates a radical-ion pair by
single-electron transfer from the donor to the acceptor.
Second, the fragmentation of the radical-ion pair produces
carboxylic radical A and radical anion B. After the release of
CO2 from carboxylic radical A, the resultant acyl radical C
added to isonitrile produces another radical intermediate D,
which undergoes the intramolecular radical cyclization to form
radical intermediate E. Then, 6-acyl phenanthridine 4 is
formed with the assistance of carboxylic radical A, along with 1
equiv of α-oxocarboxylic acid. Meanwhile, radical anion B
formed in the previous process can abstract a hydrogen cation
to generate imidoyl radical G through a resonance, which
stores a hydrogen radical. Finally, 6-acyl phenanthridine 4 is
excited under an irradiation of 3 W LED (420 5 nm) and is
reduced by 1 and G to yield the corresponding alcohol 3.
EXPERIMENTAL SECTION
■
General Information. The reactions were carried out with
magnetic stirring under a nitrogen atmosphere. All H NMR and 13
C
1
NMR spectra were recorded on a 400 or 600 MHz Bruker FT-NMR
spectrometer (400:600 and 100:150 MHz, respectively) in CDCl3 as
a solvent and recorded in parts per million relative to the internal
1
standard tetramethylsilane. H NMR data are reported as follows: δ,
chemical shift; coupling constants (J are given in hertz, Hz); and
integration. Abbreviations to denote the multiplicity of a particular
signal were s (singlet), d (doublet), t (triplet), q (quartet), m
(multiplet), and br (broad singlet). High-resolution mass spectros-
copy (HRMS) data of the products were collected on an Agilent
Technologies 6540 UHD Accurate-Mass Q-TOF LC/MS using ESI.
The chemicals and solvents were purchased from commercial
suppliers without further purification unless otherwise specified.
Products were purified by flash chromatography on 100−200 mesh
silica gels, SiO2. All manipulations that require heating for starting
materials were conducted with an oil bath. The light source was
purchased from Philips Electronics Ltd. The material of the
irradiation vessel is borosilicate glass, and the solution was placed at
a distance of ∼1.5 cm from the 3 W LED (420 5 nm).
General Experimental Procedure. General Procedure for the
Synthesis of α-Oxocarboxylic Acids 1. A representative procedure for
the preparation of 2-(4-(methylthio)phenyl)-2-oxoacetic acid is
described as follows:12 1-(p-tolyl)ethan-1-one (0.66 g, 4.0 mmol),
selenium dioxide (SeO2, 0.67 g, 6.0 mmol), and pyridine (4.0 mL)
were added to a Schlenk flask and under a N2 atmosphere. The
mixture was stirred at 110 °C for 6 h. After the reaction, the solution
was filtered and washed with EtOAc (10 mL). The combined organic
layer and volatile materials were evaporated under reduced pressure.
NaOH (2 M, 8.0 mL) was added after the concentrate. The solution
D
https://dx.doi.org/10.1021/acs.joc.0c01916
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
was extracted with EtOAc twice, and the organic layer was separated.
The combined aqueous layer was treated with HCl (12 M, 5.0 mL).
The mixture was extracted with EtOAc thrice, the combined organic
layer was dried over magnesium sulfate, and the solvent was removed
by evaporation. The residue was purified by silica gel column
chromatography (eluent: AcOEt/hexane = 10:1), and 2-oxo-2-(p-
tolyl)acetic acid (0.64 g, 81% yield) was obtained as a white solid. 1H
NMR (600 MHz, (CD3)2SO): δ 8.27 (d, J = 8.4 Hz, 2H), 8.96 (br,
1H), 7.30 (d, J = 8.4 Hz, 2H), 2.55 (s, 3H); 13C NMR (150 MHz,
(CD3)2SO): δ 182.8, 161.5, 150.4, 131.7, 127.8, 124.9, 14.5. HRMS
(ESI) [M + H]+ calcd for C9H9O3S, 197.0267; found, 197.0271.
Following the general procedure for the synthesis of 1, the crude
product was purified by silica gel column chromatography (eluent:
AcOEt/hexane = 10:1) to afford 2-(4-cyclohexylphenyl)-2-oxoacetic
acid as a yellow solid (0.79 g, 85% yield). 1H NMR (600 MHz,
(CD3)2SO): δ 8.62 (br, 1H), 8.18 (d, J = 7.8 Hz, 2H), 7.33 (d, J = 8.4
Hz, 2H), 2.56−2.59 (m, 1H), 1.87 (d, J = 7.2 Hz, 4H), 1.77 (d, J =
13.2 Hz, 1H), 1.36−1.46 (m, 4H), 1.24−1.30 (m, 1H); 13C NMR
(150 MHz, (CD3)2SO): δ 184.8, 163.4, 156.7, 131.4, 129.7, 127.5,
44.9, 33.9, 26.6, 25.9. HRMS (ESI) [M + H]+ calcd for C14H17O3,
233.1172; found, 233.1168.
trichloroethane was evaporated under reduced pressure. The resulting
crude mixture was purified by flash chromatography on silica gel
(petroleum ether/EtOAc = 5:1) to provide the desired product 3a
(55.6 mg) in 78% yield.
Phenanthridin-6-yl(phenyl)methanol (3a). White solid (55.6 mg,
78% yield); 1H NMR (400 MHz, CDCl3): δ 8.58 (d, J = 8.4 Hz, 1H),
8.54 (d, J = 8.4 Hz, 1H), 8.25 (dd, J = 8.0, 0.8 Hz, 1H), 8.00 (d, J =
8.4 Hz, 1H), 7.79−7.66 (m, 3H), 7.51 (td, J = 8.4, 1.2 Hz, 1H), 7.39−
7.37 (m, 2H), 7.29−7.22 (m, 3H), 6.55 (s, 1H), 6.39 (s, 1H);
13C{1H} NMR (100 MHz, CDCl3): δ 159.0, 143.0, 141.8, 133.4,
130.8, 129.6, 128.9, 128.8, 128.0, 127.8, 127.3, 127.2, 126.0, 124.4,
123.4, 122.5, 122.1, 72.7. HRMS (ESI) m/z: [M + H]+ calcd for
C20H16NO, 286.1226; found, 286.1222.
Phenanthridin-6-yl(p-tolyl)methanol (3b). Following the general
procedure for the synthesis of 3, the crude product was purified by
silica gel column chromatography (eluent: hexane/AcOEt = 5:1) to
afford a white solid (53.1 mg, 71% yield); 1H NMR (400 MHz,
CDCl3): δ 8.57 (d, J = 8.4 Hz, 1H), 8.53 (d, J = 8.4 Hz, 1H), 8.24
(dd, J = 8.2, 1.0 Hz, 1H), 8.00 (d, J = 8.4 Hz, 1H), 7.78−7.71 (m,
2H), 7.67 (td, J = 8.4, 1.2 Hz, 1H), 7.51 (td, J = 8.0, 0.8 Hz, 1H), 7.25
(d, J = 8.4 Hz, 2H), 7.07 (d, J = 8.0 Hz, 2H), 6.51 (s, 1H), 6.36 (s,
1H), 2.25 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 159.2,
141.8, 140.1, 137.6, 133.3, 130.7, 129.6, 129.4, 128.9, 127.7, 127.3,
127.2, 126.0, 124.4, 123.4, 122.5, 122.1, 72.5, 21.1. HRMS (ESI) m/z:
[M + H]+ calcd for C21H18NO, 300.1383; found, 300.1387.
Phenanthridin-6-yl(m-tolyl)methanol (3c). Following the general
procedure for the synthesis of 3, the crude product was purified by
silica gel column chromatography (eluent: hexane/AcOEt = 5:1) to
afford a white solid (46.4 mg, 62% yield); 1H NMR (400 MHz,
CDCl3): δ 8.55 (d, J = 8.0 Hz, 1H), 8.51 (d, J = 8.0 Hz, 1H), 8.24
(dd, J = 8.2, 0.6 Hz, 1H), 7.99 (d, J = 8.4 Hz, 1H), 7.78−7.69 (m,
2H), 7.66 (td, J = 8.0, 1.2 Hz, 1H), 7.49 (td, J = 8.0, 1.2 Hz, 1H),
7.18−7.13 (m, 3H), 7.04−7.03 (m, 1H), 6.53 (s, 1H), 6.34 (s, 1H),
2.24 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 159.1, 142.9,
141.8, 138.4, 133.3, 130.7, 129.6, 128.9, 128.8, 128.6, 128.4, 127.3,
127.2, 126.0, 124.9, 124.4, 123.4, 122.4, 122.1, 72.8, 21.3. HRMS
(ESI) m/z: [M + H]+ calcd for C21H18NO, 300.1383; found,
300.1383.
General Procedure for the Synthesis of 2-Arylisocyanides 2. All
2-arylisocyanides were prepared according to a reported method.13
A
representative procedure for the preparation of 4′-chloro-2-isocyano-
1,1′-biphenyl (2b) is described as follows: 2-iodoaniline (1.10 g, 5.0
mmol), (4-chlorophenyl)boronic acid (0.94 g, 6.0 mmol, 1.2 equiv),
Pd(PPh3)2Cl2 (70.2 mg, 0.10 mmol, 0.02 equiv), and K2CO3 (2 M, 10
mL) were added to a Schlenk flask and dissolved in 1,2-
dimethoxyethane (5 mL) under a N2 atmosphere. The mixture was
stirred at 80 °C for 16 h. After the reaction, water was added and
extracted with EtOAc twice. The combined organic layer was dried
over magnesium sulfate, and the solvent was removed by evaporation.
The residue was purified by silica gel column chromatography
(eluent: hexane/AcOEt = 5:1), and 4′-chloro-[1,1′-biphenyl]-2-amine
(0.86 g, 84%) was obtained as a white solid.
In a 50 mL two-necked flask, acetic formic anhydride, which was
prepared from the reaction of acetic anhydride (0.50 mL) with formic
acid (0.60 mL) at room temperature for 10 min, was added dropwise
to a stirred a solution of 4′-chloro-[1,1′-biphenyl]-2-amine (4.0
mmol, 0.81 g) in CH2Cl2 (10.0 mL), and the mixture was stirred at
room temperature for 2 h. After the reaction, volatile materials were
evaporated under reduced pressure. N-(4′-Chloro-[1,1′-biphenyl]-2-
yl)-formamide (0.83 g, 90%) was obtained as a white solid. This
compound was used for the subsequent dehydration without further
purification.
N-(4′-Chloro-[1,1′-biphenyl]-2-yl)formamide (0.70 g, 3.0 mmol)
was dissolved in CHCl3 (10.0 mL) and Et3N (2.4 mL, 16 mmol)
under a N2 atmosphere and cooled to 0 °C in an ice bath. Then,
phosphoryl chloride (0.72 mL, 7.2 mmol, 3.0 mL of CHCl3 solution)
was added dropwise slowly to this mixture. After stirring for 1 h, the
reaction temperature was down to room temperature and the mixture
was stirred for another 1 h. After the reaction, the resulting mixture
was cooled to 0 °C in an ice bath. Then, the mixture was quenched
and neutralized by a saturated aqueous solution of Na2CO3. After
vigorous stirring for 1 h, water (10.0 mL) was added and the organic
layer was separated. The aqueous layer was extracted with CH2Cl2
(10.0 mL) twice. The combined organic layer was dried over sodium
sulfate, and the solvent was removed by evaporation. The residue was
purified by silica gel column chromatography (eluent: hexane/AcOEt
= 20:1). 4′-Chloro-2-isocyano-1,1′-biphenyl (2b, 0.45 g, 70%) was
obtained as a white solid.
General Procedure for Synthesis of 3. A typical experimental
procedure for the synthesis of 3a is described as follows:
phenylglyoxylic acid (1a, 0.75 mmol), 2-isocyanobiphenyl (2a, 0.25
mmol), and pyridine (6.0 equiv) were added into an air-tight reaction
tube (10 mL) with 2.0 mL of 1,1,2-trichloroethane. The tube
containing the reactants and solvent was evacuated using a pump and
back-filled with high-purified nitrogen (>99.99%). The reaction
mixture was stirred at room temperature under irradiation with a 3
(4-Ethylphenyl)(phenanthridin-6-yl)methanol (3d). Following the
general procedure for the synthesis of 3, the crude product was
purified by silica gel column chromatography (eluent: hexane/AcOEt
1
= 5:1) to afford a white solid (52.5 mg, 67% yield); H NMR (400
MHz, CDCl3): δ 8.57 (d, J = 8.4 Hz, 1H), 8.53 (d, J = 8.4 Hz, 1H),
8.24 (dd, J = 8.0, 1.2 Hz, 1H), 8.02 (d, J = 8.0 Hz, 1H), 7.79−7.72
(m, 2H), 7.69 (td, J = 8.4, 1.2 Hz, 1H), 7.51 (td, J = 8.4, 1.2 Hz, 1H),
7.28 (d, J = 8.0 Hz, 2H), 7.10 (d, J = 8.4 Hz, 2H), 6.50 (s, 1H), 6.37
(s, 1H), 2.56 (q, J = 7.6 Hz, 2H), 1.15 (t, J = 7.2 Hz, 3H); 13C{1H}
NMR (100 MHz, CDCl3): δ 159.2, 144.0, 141.8, 140.3, 133.3, 130.7,
129.6, 128.9, 128.3, 127.8, 127.3, 127.2, 126.0, 124.4, 123.5, 122.5,
122.1, 72.5, 28.5, 15.3. HRMS (ESI) m/z: [M + H]+ calcd for
C22H20NO, 314.1539; found, 314.1543.
(4-(tert-Butyl)phenyl)(phenanthridin-6-yl)methanol (3e). Follow-
ing the general procedure for the synthesis of 3, the crude product was
purified by silica gel column chromatography (eluent: hexane/AcOEt
1
= 5:1) to afford a white solid (69.1 mg, 81% yield); H NMR (400
MHz, CDCl3): δ 8.54 (d, J = 8.4 Hz, 1H), 8.50 (d, J = 8.0 Hz, 1H),
8.23 (dd, J = 8.0, 0.8 Hz, 1H), 8.02 (d, J = 8.0 Hz, 1H), 7.77−7.69
(m, 2H), 7.65 (td, J = 8.0, 0.8 Hz, 1H), 7.50 (t, J = 7.6 Hz, 1H),
7.31−7.27 (m, 4H), 6.49 (s, 1H), 6.38 (s, 1H), 1.23 (s, 9H); 13C{1H}
NMR (100 MHz, CDCl3): δ 159.2, 150.8, 141.8, 139.9, 133.3, 130.7,
129.6, 128.8, 127.4, 127.3, 127.1, 126.0, 125.7, 124.4, 123.5, 122.4,
122.1, 72.3, 34.4, 31.2. HRMS (ESI) m/z: [M + H]+ calcd for
C24H24NO, 342.1852; found, 342.1854.
(4-Cyclohexylphenyl)(phenanthridin-6-yl)methanol (3f). Follow-
ing the general procedure for the synthesis of 3, the crude product was
purified by silica gel column chromatography (eluent: hexane/AcOEt
1
= 5:1) to afford a white solid (63.4 mg, 69% yield); H NMR (400
MHz, CDCl3): δ 8.54 (d, J = 8.4 Hz, 1H), 8.51 (d, J = 7.6 Hz, 1H),
8.23 (d, J = 8.0 Hz, 1H), 8.01 (d, J = 8.0 Hz, 1H), 7.77−7.69 (m,
2H), 7.66 (td, J = 8.4, 1.2 Hz, 1H), 7.49 (td, J = 8.0, 0.8 Hz, 1H), 7.28
W LED (420
5 nm) for 10 h. After the reaction, 1,1,2-
E
https://dx.doi.org/10.1021/acs.joc.0c01916
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(d, J = 8.0 Hz, 2H), 7.10 (d, J = 8.0 Hz, 2H), 6.50 (br, 1H), 6.36 (s,
1H), 2.40 (br, 1H), 1.77−1.67 (m, 5H), 1.42−1.22 (m, 5H);
13C{1H} NMR (100 MHz, CDCl3): δ 159.2, 147.7, 141.8, 140.3,
133.3, 130.7, 129.5, 128.8, 127.6, 127.1, 126.0, 124.4, 123.4, 122.4,
122.1, 72.4, 44.2, 26.8, 26.1. HRMS (ESI) m/z: [M + H]+ calcd for
C26H26NO, 368.2009; found, 368.2009.
(4-Bromophenyl)(phenanthridin-6-yl)methanol (3l). Following
the general procedure for the synthesis of 3, the crude product was
purified by silica gel column chromatography (eluent: hexane/AcOEt
1
= 5:1) to afford a white solid (66.5 mg, 73% yield); H NMR (400
MHz, CDCl3): δ 8.62 (d, J = 8.4 Hz, 1H), 8.57 (d, J = 7.2 Hz, 1H),
8.24 (dd, J = 8.0, 1.2 Hz, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.79 (t, J =
8.0 Hz, 2H), 7.71 (td, J = 8.4, 1.2 Hz, 1H), 7.55 (td, J = 8.4, 1.2 Hz,
1H), 7.40 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.4 Hz, 2H), 6.54 (s, 1H),
6.35 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 158.4, 142.0,
141.7, 133.5, 131.9, 130.9, 129.60, 129.55, 129.1, 127.5, 127.4, 125.7,
124.5, 123.2, 122.7, 122.2, 122.0, 72.0. HRMS (ESI) m/z: [M + H]+
calcd for C20H15BrNO, 364.0332; found, 364.0334.
(4-Methoxyphenyl)(phenanthridin-6-yl)methanol (3g). Follow-
ing the general procedure for the synthesis of 3, the crude product was
purified by silica gel column chromatography (eluent: hexane/AcOEt
1
= 5:1) to afford a white solid (66.2 mg, 84% yield); H NMR (400
MHz, CDCl3): δ 8.55 (d, J = 8.4 Hz, 1H), 8.51 (d, J = 8.4 Hz, 1H),
8.23 (d, J = 8.0 Hz, 1H), 7.97 (d, J = 8.0 Hz, 1H), 7.77−7.70 (m,
2H), 7.66 (td, J = 8.0, 1.2 Hz, 1H), 7.49 (td, J = 8.0, 0.8 Hz, 1H), 7.28
(d, J = 8.8 Hz, 2H), 6.79 (d, J = 8.4 Hz, 2H), 6.50 (s, 1H), 6.35 (s,
1H), 3.69 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 159.23,
159.22, 141.7, 135.4, 133.3, 130.7, 129.5, 129.0, 128.9, 127.3, 127.1,
126.0, 124.4, 123.4, 122.4, 122.1, 114.1, 72.2, 55.1. HRMS (ESI) m/z:
[M + H]+ calcd for C21H18NO2, 316.1332; found, 316.1330.
(4-(Methylthio)phenyl)(phenanthridin-6-yl)methanol (3h). Fol-
lowing the general procedure for the synthesis of 3, the crude product
was purified by silica gel column chromatography (eluent: hexane/
AcOEt = 5:1) to afford a white solid (53.9 mg, 65% yield); 1H NMR
(400 MHz, CDCl3): δ 8.53 (d, J = 8.4 Hz, 1H), 8.49 (d, J = 8.0 Hz,
1H), 8.21 (dd, J = 8.0, 0.8 Hz, 1H), 7.95 (d, J = 8.4 Hz, 1H), 7.76−
7.68 (m, 2H), 7.64 (td, J = 8.0, 0.8 Hz, 1H), 7.48 (t, J = 7.2 Hz, 1H),
7.27 (d, J = 8.4 Hz, 2H), 7.13 (d, J = 8.4 Hz, 2H), 6.51 (s, 1H), 6.33
(s, 1H), 2.35 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 158.8,
141.6, 139.8, 138.2, 133.2, 130.7, 129.5, 128.9, 128.2, 127.3, 127.2,
126.7, 125.8, 124.3, 123.2, 122.4, 122.0, 72.2, 15.6. HRMS (ESI) m/z:
[M + H]+ calcd for C21H18NOS, 332.1104; found, 332.1103.
(4-Iodophenyl)(phenanthridin-6-yl)methanol (3m). Following
the general procedure for the synthesis of 3, the crude product was
purified by silica gel column chromatography (eluent: hexane/AcOEt
1
= 5:1) to afford a white solid (51.4 mg, 50% yield); H NMR (400
MHz, CDCl3): δ 8.61 (d, J = 8.4 Hz, 1H), 8.56 (d, J = 8.0 Hz, 1H),
8.24 (d, J = 8.0 Hz, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.78 (t, J = 7.6 Hz,
2H), 7.70 (t, J = 8.4 Hz, 1H), 7.60 (d, J = 8.4 Hz, 2H), 7.55 (t, J = 8.0
Hz, 1H), 7.12 (d, J = 8.4 Hz, 2H), 6.53 (s, 1H), 6.33 (s, 1H);
13C{1H} NMR (100 MHz, CDCl3): δ 158.4, 142.6, 141.7, 137.9,
133.4, 130.9, 129.8, 129.6, 129.0, 127.5, 127.4, 125.7, 124.5, 123.2,
122.7, 122.2, 93.7, 72.2. HRMS (ESI) m/z: [M + H]+ calcd for
C20H15INO, 412.0193; found, 412.0194.
(3,5-Dimethylphenyl)(phenanthridin-6-yl)methanol (3n). Fol-
lowing the general procedure for the synthesis of 3, the crude
product was purified by silica gel column chromatography (eluent:
hexane/AcOEt = 5:1) to afford a white solid (50.9 mg, 65% yield); 1H
NMR (400 MHz, CDCl3): δ 8.55 (d, J = 8.4 Hz, 1H), 8.51 (d, J = 8.0
Hz, 1H), 8.25 (dd, J = 8.0, 0.8 Hz, 1H), 8.01 (d, J = 8.0 Hz, 1H),
7.78−7.70 (m, 2H), 7.66 (td, J = 8.0, 1.2 Hz, 1H), 7.50 (td, J = 8.0,
0.8 Hz, 1H), 6.97 (br, 2H), 6.85 (s, 1H), 6.52 (s, 1H), 6.30 (s, 1H),
2.20 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3): δ 159.1, 142.8,
141.7, 138.3, 133.3, 130.6, 129.7, 129.6, 128.8, 127.3, 127.1, 126.0,
125.6, 124.4, 123.5, 122.4, 122.1, 72.8, 21.2. HRMS (ESI) m/z: [M +
H]+ calcd for C22H20NO, 314.1539; found, 314.1539.
(4-Fluorophenyl)(phenanthridin-6-yl)methanol (3i). Following
the general procedure for the synthesis of 3, the crude product was
purified by silica gel column chromatography (eluent: hexane/AcOEt
1
= 5:1) to afford a white solid (45.5 mg, 60% yield); H NMR (400
MHz, CDCl3): δ 8.58 (d, J = 8.4 Hz, 1H), 8.53 (d, J = 7.2 Hz, 1H),
8.23 (dd, J = 8.0, 1.2 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.79−7.73
(m, 2H), 7.68 (td, J = 8.0, 1.2 Hz, 1H), 7.52 (td, J = 8.0, 0.8 Hz, 1H),
7.35−7.32 (m, 2H), 6.95 (t, J = 8.8 Hz, 2H), 6.53 (s, 1H), 6.37 (s,
Phenanthridin-6-yl(thiophen-2-yl)methanol (3o). Following the
general procedure for the synthesis of 3, the crude product was
purified by silica gel column chromatography (eluent: hexane/AcOEt
1H); 13C{1H} NMR (100 MHz, CDCl3): δ 162.4 (C−F, 1JC−F
=
1
= 5:1) to afford a yellow solid (24.6 mg, 34% yield); H NMR (600
246.0 Hz), 158.8, 141.7, 138.9 (C−F, 3JC−F = 3.0 Hz), 133.4, 130.8,
129.6 (C−F, 3JC−F = 2.0 Hz), 129.5, 129.0, 127.4, 127.3, 125.8, 124.4,
123.2, 122.6, 122.1, 115.6 (C−F, 2JC−F = 21.3 Hz), 71.9. HRMS
(ESI) m/z: [M + H]+ calcd for C20H15FNO, 304.1132; found,
304.1127.
MHz, CDCl3): δ 8.64 (d, J = 8.4 Hz, 1H), 8.57 (d, J = 8.4 Hz, 1H),
8.22 (d, J = 7.8 Hz, 1H), 8.11 (d, J = 7.8 Hz, 1H), 7.82 (td, J = 8.4
Hz, 1H), 7.78 (td, J = 7.2 Hz, 1H), 7.70 (t, J = 7.8 Hz, 1H), 7.60 (t, J
= 8.4 Hz, 1H), 7.20 (d, J = 5.4 Hz, 1H), 6.96 (d, J = 3.6 Hz, 1H),
6.89−6.87 (m, 1H), 6.68 (s, 1H), 6.46 (s, 1H); 13C{1H} NMR (150
MHz, CDCl3): δ 158.4, 147.0, 141.9, 133.5, 131.0, 129.7, 129.0,
127.5, 127.4, 126.7, 125.9, 125.8, 124.5, 123.4, 122.6, 122.1, 67.6.
HRMS (ESI) m/z: [M + H]+ calcd for C18H14NOS, 292.0791; found,
292.0789.
(4-Chlorophenyl)(phenanthridin-6-yl)methanol (3j). Following
the general procedure for the synthesis of 3, the crude product was
purified by silica gel column chromatography (eluent: hexane/AcOEt
1
= 5:1) to afford a white solid (46.4 mg, 58% yield); H NMR (400
MHz, CDCl3): δ 8.62 (d, J = 8.4 Hz, 1H), 8.57 (d, J = 8.0 Hz, 1H),
8.24 (d, J = 7.2 Hz, 1H), 7.95 (d, J = 8.0 Hz, 1H), 7.79 (t, J = 7.6 Hz,
2H), 7.71 (td, J = 8.0, 1.2 Hz, 1H), 7.55 (t, J = 7.6 Hz, 1H), 7.31 (d, J
= 8.4 Hz, 2H), 7.24 (d, J = 8.4 Hz, 2H), 6.53 (s, 1H), 6.36 (s, 1H);
13C{1H} NMR (100 MHz, CDCl3): δ 158.5, 141.7, 141.5, 133.8,
133.5, 130.9, 129.6, 129.2, 129.1, 129.0, 127.5, 127.4, 125.8, 124.5,
123.2, 122.7, 122.2, 72.0. HRMS (ESI) m/z: [M + H]+ calcd for
C20H15ClNO, 320.0837; found, 320.0833.
(2-Methylphenanthridin-6-yl)(phenyl)methanol (3p). Following
the general procedure for the synthesis of 3, the crude product was
purified by silica gel column chromatography (eluent: hexane/AcOEt
1
= 5:1) to afford a white solid (45.7 mg, 61% yield); H NMR (400
MHz, CDCl3): δ 8.50 (d, J = 8.0 Hz, 1H), 8.26 (s, 1H), 8.10 (d, J =
8.0 Hz, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.66 (td, J = 8.0, 0.8 Hz, 1H),
7.55 (dd, J = 8.2, 1.4 Hz, 1H), 7.44 (t, J = 8.0 Hz, 1H), 7.36 (d, J =
6.8 Hz, 2H), 7.27−7.20 (m, 3H), 6.57 (s, 1H), 6.35 (s, 1H), 2.59 (s,
3H); 13C{1H} NMR (100 MHz, CDCl3): δ 157.9, 143.1, 140.0,
137.1, 133.0, 130.5, 130.4, 129.2, 128.7, 127.9, 127.8, 127.1, 125.8,
124.2, 123.4, 122.4, 121.7, 72.6, 21.9. HRMS (ESI) m/z: [M + H]+
calcd for C21H18NO, 300.1383; found, 300.1383.
(3-Chlorophenyl)(phenanthridin-6-yl)methanol (3k). Following
the general procedure for the synthesis of 3, the crude product was
purified by silica gel column chromatography (eluent: hexane/AcOEt
1
= 5:1) to afford a white solid (44.0 mg, 55% yield); H NMR (400
MHz, CDCl3): δ 8.62 (d, J = 8.4 Hz, 1H), 8.57 (d, J = 8.4 Hz, 1H),
8.25 (dd, J = 8.4, 0.8 Hz, 1H), 7.97 (d, J = 8.0 Hz, 1H), 7.80 (t, J =
7.2 Hz, 2H), 7.71 (td, J = 8.4, 1.2 Hz, 1H), 7.57 (td, J = 8.0, 0.8 Hz,
1H), 7.36 (s, 1H), 7.29−7.27 (m, 1H), 7.22−7.20 (m, 2H), 6.54 (s,
1H), 6.35 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 158.3,
144.9, 141.7, 134.6, 133.5, 131.0, 130.1, 129.6, 129.1, 128.2, 128.0,
127.51, 127.46, 126.1, 125.7, 124.5, 123.2, 122.7, 122.2, 72.2. HRMS
(ESI) m/z: [M + H]+ calcd for C20H14ClNO, 320.0837; found,
320.0834.
(2-Fluorophenanthridin-6-yl)(phenyl)methanol (3q). Following
the general procedure for the synthesis of 3, the crude product was
purified by silica gel column chromatography (eluent: hexane/AcOEt
1
= 5:1) to afford a white solid (51.6 mg, 68% yield); H NMR (400
MHz, CDCl3): δ 8.36 (d, J = 8.4 Hz, 1H), 8.20−8.17 (m, 1H), 8.06
(dd, J = 10.0, 2.8 Hz, 1H), 7.98 (d, J = 8.0 Hz, 1H), 7.70 (td, J = 8.4,
0.8 Hz, 1H), 7.53−7.44 (m, 2H), 7.36 (d, J = 6.8 Hz, 2H), 7.29−7.22
(m, 3H), 6.39 (s, 1H), 6.36 (s, 1H); 13C{1H} NMR (100 MHz,
CDCl3): δ 161.4 (C−F, 1JC−F = 245.9 Hz), 158.3, 142.8, 138.5, 132.7
F
https://dx.doi.org/10.1021/acs.joc.0c01916
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(C−F, 4JC−F = 4.3 Hz), 131.7 (C−F, 3JC−F = 9.0 Hz), 130.7, 128.8,
128.0, 127.9, 127.7, 125.9, 125.7 (C−F, 3JC−F = 9.0 Hz), 123.3, 122.6,
117.7 (C−F, 2JC−F = 24.2 Hz), 107.1 (C−F, 2JC−F = 23.4 Hz), 72.7.
HRMS (ESI) m/z: [M + H]+ calcd for C20H15FNO, 304.1132; found,
304.1128.
8.6, 1.4 Hz, 1H), 7.86 (td, J = 8.4, 1.2 Hz, 1H), 7.75 (td, J = 8.0, 1.2
Hz, 1H), 7.40 (d, J = 8.4 Hz, 2H), 7.32−7.22 (m, 3H), 6.40 (br, 2H);
13C{1H} NMR (100 MHz, CDCl3): δ 159.2, 142.5, 142.4, 135.6,
130.2, 129.9, 129.1 (C−F, 2JC−F = 32.8 Hz), 129.0, 128.3, 127.9,
127.7, 126.7 (C−F, 3JC−F = 3.0 Hz), 123.65(C−F, 1JC−F = 271.0 Hz),
123.66, 123.5(C−F, 4JC−F = 4.3 Hz), 122.7, 122.5, 72.9. HRMS (ESI)
m/z: [M + H]+ calcd for C21H15F3NO, 354.1100; found, 354.1102.
(8-Fluorophenanthridin-6-yl)(phenyl)methanol (3x). Following
the general procedure for the synthesis of 3, the crude product was
purified by silica gel column chromatography (eluent: hexane/AcOEt
(2-Chlorophenanthridin-6-yl)(phenyl)methanol (3r). Following
the general procedure for the synthesis of 3, the crude product was
purified by silica gel column chromatography (eluent: hexane/AcOEt
1
= 5:1) to afford a white solid (56.8 mg, 71% yield); H NMR (400
MHz, CDCl3): δ 8.41−8.38 (m, 2H), 8.12 (d, J = 8.8 Hz, 1H), 7.98
(d, J = 8.4 Hz, 1H), 7.72−7.66 (m, 2H), 7.51 (t, J = 8.0 Hz, 1H), 7.36
(d, J = 6.8 Hz, 2H), 7.29−7.22 (m, 3H), 6.36 (br, 2H); 13C{1H}
NMR (100 MHz, CDCl3): δ 159.4, 142.7, 140.1, 133.1, 132.2, 131.0,
130.9, 129.4, 128.8, 128.03, 127.95, 127.7, 126.0, 125.4, 123.4, 122.4,
121.7, 72.7. HRMS (ESI) m/z: [M + H]+ calcd for C20H15ClNO,
320.0837; found, 320.0835.
1
= 5:1) to afford a white solid (52.3 mg, 69% yield); H NMR (400
MHz, CDCl3): δ 8.50−8.47 (m, 1H), 8.40 (d, J = 8.4 Hz, 1H), 8.22
(d, J = 8.0 Hz, 1H), 7.74 (t, J = 7.6 Hz, 1H), 7.65 (t, J = 7.6 Hz, 1H),
7.58 (dd, J = 9.6, 2.4 Hz, 1H), 7.43 (td, J = 8.8, 2.4 Hz, 1H), 7.37 (d, J
= 7.2 Hz, 2H), 7.30−7.22 (m, 3H), 6.44 (s, 1H), 6.26 (s, 1H);
13C{1H} NMR (100 MHz, CDCl3): δ 160.9 (C−F, 1JC−F = 247.6
(2-Chlorophenanthridin-6-yl)(4-methoxyphenyl)methanol (3s).
Following the general procedure for the synthesis of 3, the crude
product was purified by silica gel column chromatography (eluent:
hexane/AcOEt = 5:1) to afford a white solid (74.3 mg, 85% yield); 1H
NMR (400 MHz, CDCl3): δ 8.43−8.41 (m, 2H), 8.12 (d, J = 8.8 Hz,
1H), 7.98 (d, J = 8.0 Hz, 1H), 7.72 (td, J = 8.4, 1.2 Hz, 1H), 7.68 (dd,
J = 8.6, 2.2 Hz, 1H), 7.53 (td, J = 8.0, 0.8 Hz, 1H), 7.26 (d, J = 8.8 Hz,
2H), 6.80 (d, J = 8.8 Hz, 2H), 6.33−6.29 (m, 2H), 3.71 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3): δ 159.6, 159.3, 140.1, 135.1,
133.1, 132.2, 130.9, 129.3, 129.0, 127.9, 126.1, 125.4, 123.4, 122.5,
121.7, 114.2, 72.2, 55.1. HRMS (ESI) m/z: [M + H]+ calcd for
C21H17ClNO2, 350.0942; found, 350.0943.
Hz), 158.2 (C−F, 4JC−F = 4.0 Hz), 142.3, 141.3, 129.9 (C−F, 4JC−F
1.8 Hz), 129.6, 128.9, 128.8, 128.2, 127.7, 127.6, 125.0 (C−F, 3JC−F
=
=
8.5 Hz), 124.5(d, J = 8.1 Hz), 123.9, 121.8, 120.0 (C−F, 2JC−F = 23.8
Hz), 110.6 (C−F, 2JC−F = 21.7 Hz), 72.8. HRMS (ESI) m/z: [M +
H]+ calcd for C20H15FNO, 304.1132; found, 304.1134.
(8-Chlorophenanthridin-6-yl)(phenyl)methanol (3y). Following
the general procedure for the synthesis of 3, the crude product was
purified by silica gel column chromatography (eluent: hexane/AcOEt
1
= 5:1) to afford a white solid (43.2 mg, 54% yield); H NMR (400
MHz, CDCl3): δ 8.48 (t, J = 8.8 Hz, 2H), 8.24 (d, J = 8.4 Hz, 1H),
7.97 (d, J = 2.0 Hz, 1H), 7.79 (td, J = 8.0, 0.8 Hz, 1H), 7.72−7.67 (m,
2H), 7.38 (d, J = 7.2 Hz, 2H), 7.32−7.23 (m, 3H), 6.39 (s, 1H), 6.31
(s, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 158.1, 142.4, 141.7,
133.3, 131.7, 131.4, 129.7, 129.3, 128.9, 128.2, 127.74, 127.69, 125.3,
124.33, 124.27, 123.8, 122.0, 72.7. HRMS (ESI) m/z: [M + H]+ calcd
for C20H15ClNO, 320.0837; found, 320.0837.
(8-(Methylthio)phenanthridin-6-yl)(phenyl)methanol (3z). Fol-
lowing the general procedure for the synthesis of 3, the crude
product was purified by silica gel column chromatography (eluent:
hexane/AcOEt = 5:1) to afford a white solid (50.5 mg, 61% yield); 1H
NMR (400 MHz, CDCl3): δ 8.47 (d, J = 8.0 Hz, 1H), 8.43 (d, J = 8.8
Hz, 1H), 8.23 (d, J = 8.0 Hz, 1H), 7.75 (td, J = 8.4, 1.2 Hz, 1H),
7.69−7.58 (m, 3H), 7.36 (d, J = 6.8 Hz, 2H), 7.31−7.24 (m, 3H),
6.61 (s, 1H), 6.29 (s, 1H), 2.38 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3): δ 157.9, 142.9, 141.3, 138.8, 130.6, 129.6, 128.9, 128.6,
128.1, 127.9, 127.4, 124.3, 123.9, 122.7, 121.8, 121.1, 73.0, 15.3.
HRMS (ESI) m/z: [M + H]+ calcd for C21H18NOS, 332.1104; found,
332.1104.
(8-Methylphenanthridin-6-yl)(phenyl)methanol (3t). Following
the general procedure for the synthesis of 3, the crude product was
purified by silica gel column chromatography (eluent: hexane/AcOEt
1
= 5:1) to afford a white solid (53.9 mg, 72% yield); H NMR (400
MHz, CDCl3): δ 8.45 (d, J = 8.4 Hz, 1H), 8.40 (d, J = 8.4 Hz, 1H),
8.20 (dd, J = 8.4, 0.8 Hz, 1H), 7.74−7.69 (m, 2H), 7.63 (td, J = 8.4,
1.6 Hz, 1H), 7.51 (d, J = 8.4 Hz, 1H), 7.38 (t, J = 7.6 Hz, 2H), 7.27
(t, J = 6.8 Hz, 2H), 7.23−7.19 (m, 1H), 6.57 (s, 1H), 6.35 (s, 1H),
2.40 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 158.6, 143.0,
141.4, 137.3, 132.5, 131.2, 129.4, 128.7, 128.4, 127.9, 127.8, 127.1,
125.3, 124.5, 123.5, 122.3, 121.9, 72.6, 21.7. HRMS (ESI) m/z: [M +
H]+ calcd for C21H18NO, 300.1383; found, 300.1384.
(8-Methoxyphenanthridin-6-yl)(phenyl)methanol (3u). Follow-
ing the general procedure for the synthesis of 3, the crude product was
purified by silica gel column chromatography (eluent: hexane/AcOEt
1
= 5:1) to afford a white solid (52.0 mg, 66% yield); H NMR (400
MHz, CDCl3): δ 8.42−8.39 (m, 2H), 8.21 (d, J = 8.0 Hz, 1H), 7.69
(t, J = 7.2 Hz, 1H), 7.63 (t, J = 7.6 Hz, 1H), 7.39 (d, J = 7.2 Hz, 2H),
7.32−7.23 (m, 5H), 6.68 (s, 1H), 6.26 (s, 1H), 3.71 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3): δ 158.2, 157.9, 142.9, 140.8, 129.4, 128.8,
128.0, 127.8, 127.6, 127.2, 124.50, 124.47, 124.0, 121.5, 121.4, 106.0,
73.0, 55.2. HRMS (ESI) m/z: [M + H]+ calcd for C21H18NO2,
316.1332; found, 316.1333.
(8-Methoxyphenanthridin-6-yl)(p-tolyl)methanol (3aa). Follow-
ing the general procedure for the synthesis of 3, the crude product was
purified by silica gel column chromatography (eluent: hexane/AcOEt
1
= 5:1) to afford a yellow solid (56.0 mg, 68% yield); H NMR (400
MHz, CDCl3): δ 8.43 (t, J = 8.8 Hz, 2H), 8.21 (d, J = 8.0 Hz, 1H),
7.70 (td, J = 8.0, 0.8 Hz, 1H), 7.64 (td, J = 8.0, 1.2 Hz, 1H), 7.33 (dd,
J = 8.8, 2.4 Hz, 1H), 7.28−7.26 (m, 3H), 7.08 (d, J = 8.0 Hz, 2H),
6.62 (s, 1H), 6.24 (s, 1H), 3.74 (s, 3H), 2.26 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3): δ 158.3, 158.1, 140.9, 140.0, 137.7, 129.5, 127.8,
127.7, 127.6, 127.2, 124.6, 124.5, 124.0, 121.6, 121.4, 106.1, 72.8,
55.3, 21.1. HRMS (ESI) m/z: [M + H]+ calcd for C22H20NO2,
330.1489; found, 330.1484.
(4-Chlorophenyl)(8-methoxyphenanthridin-6-yl)methanol
(3ab). Following the general procedure for the synthesis of 3, the
crude product was purified by silica gel column chromatography
(eluent: hexane/AcOEt = 5:1) to afford a white solid (61.2 mg, 70%
yield); 1H NMR (400 MHz, CDCl3): δ 8.49 (d, J = 9.2 Hz, 1H), 8.46
(d, J = 8.0 Hz, 1H), 8.21 (dd, J = 7.8, 1.0 Hz, 1H), 7.72 (td, J = 7.2,
1.6 Hz, 1H), 7.70 (td, J = 8.0, 1.2 Hz, 1H), 7.38 (dd, J = 9.0, 2.6 Hz,
1H), 7.32 (d, J = 8.8 Hz, 2H), 7.25 (d, J = 8.4 Hz, 2H), 7.20 (d, J =
2.4 Hz, 1H), 6.64 (s, 1H), 6.25 (s, 1H), 3.77 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3): δ 158.4, 157.5, 141.5, 140.8, 133.9, 129.5, 129.2,
129.0, 128.0, 127.8, 127.4, 124.6, 124.4, 124.3, 121.6, 121.5, 106.0,
72.2, 55.4. HRMS (ESI) m/z: [M + H]+ calcd for C21H17ClNO2,
350.0942; found, 350.0941.
(8-(tert-Butyl)phenanthridin-6-yl)(phenyl)methanol (3v). Follow-
ing the general procedure for the synthesis of 3, the crude product was
purified by silica gel column chromatography (eluent: hexane/AcOEt
1
= 5:1) to afford a white solid (68.3 mg, 80% yield); H NMR (400
MHz, CDCl3): δ 8.43 (d, J = 3.6 Hz, 1H), 8.41 (d, J = 4.4 Hz, 1H),
8.19 (dd, J = 8.0, 0.8 Hz, 1H), 7.96 (d, J = 2.0 Hz, 1H), 7.75 (dd, J =
8.8, 2.0 Hz, 1H), 7.67 (td, J = 7.2, 1.2 Hz, 1H), 7.58 (td, J = 8.4, 1.2
Hz, 1H), 7.42−7.40 (m, 2H), 7.24 (t, J = 7.2 Hz, 2H), 7.20−7.16 (m,
1H), 6.74 (s, 1H), 6.36 (s, 1H), 1.26 (s, 9H); 13C{1H} NMR (100
MHz, CDCl3): δ 159.0, 150.1, 143.1, 141.4, 131.1, 129.3, 128.9,
128.6, 128.3, 127.82, 127.78, 127.0, 124.3, 123.1, 122.2, 121.9, 73.0,
34.9, 31.0. HRMS (ESI) m/z: [M + H]+ calcd for C24H24NO,
342.1852; found, 342.1854.
Phenyl(8-(trifluoromethyl)phenanthridin-6-yl)methanol (3w).
Following the general procedure for the synthesis of 3, the crude
product was purified by silica gel column chromatography (eluent:
hexane/AcOEt = 5:1) to afford a white solid (53.9 mg, 61% yield); 1H
NMR (400 MHz, CDCl3): δ 8.69 (d, J = 8.8 Hz, 1H), 8.55 (d, J = 8.0
Hz, 1H), 8.34 (s, 1H), 8.29 (dd, J = 8.4, 0.8 Hz, 1H), 7.94 (dd, J =
G
https://dx.doi.org/10.1021/acs.joc.0c01916
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(8-Fluoro-2-methylphenanthridin-6-yl)(phenyl)methanol (3ac).
Following the general procedure for the synthesis of 3, the crude
product was purified by silica gel column chromatography (eluent:
hexane/AcOEt = 5:1) to afford a white solid (46.0 mg, 58% yield); 1H
NMR (400 MHz, CDCl3): δ 8.54 (dd, J = 9.2, 5.6 Hz, 1H), 8.24 (s,
1H), 8.13 (d, J = 8.4 Hz, 1H), 7.58 (td, J = 9.2, 1.8 Hz, 2H), 7.46 (td,
J = 9.2, 2.8 Hz, 1H), 7.36 (d, J = 7.2 Hz, 2H), 7.31−7.24 (m, 3H),
6.46 (s, 1H), 6.26 (s, 1H), 2.63 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3): δ 160.9 (C−F, 1JC−F = 247.4 Hz), 157.1, 142.5, 139.7, 137.7,
130.5, 129.8, 129.4, 129.0, 128.2, 127.8, 125.1 (C−F, 3JC−F = 8.5 Hz),
124.6 (C−F, 3JC−F = 8.1 Hz), 123.9, 121.5, 119.8 (C−F, 2JC−F = 23.8
Hz), 110.5 (C−F, 2JC−F = 21.7 Hz), 72.8, 22.0. HRMS (ESI) m/z:
[M + H]+ calcd for C21H17FNO, 318.1289; found, 318.1288.
(2-Fluoro-8-methylphenanthridin-6-yl)(phenyl)methanol (3ad).
Following the general procedure for the synthesis of 3, the crude
product was purified by silica gel column chromatography (eluent:
hexane/AcOEt = 5:1) to afford a white solid (47.6 mg, 60% yield); 1H
NMR (400 MHz, CDCl3): δ 8.23 (d, J = 8.4 Hz, 1H), 8.17 (dd, J =
8.8, 5.6 Hz, 1H), 8.01 (dd, J = 10.0, 2.4 Hz, 1H), 7.74 (s, 1H), 7.50
(d, J = 8.4 Hz, 1H), 7.44 (td, J = 8.4, 2.4 Hz, 1H), 7.38 (d, J = 7.2 Hz,
2H), 7.30−7.22 (m, 3H), 6.43 (d, J = 4.8 Hz, 1H), 6.33 (d, J = 4.8
Hz, 1H), 2.41 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 161.4
(C−F, 1JC−F = 245.7 Hz), 158.0 (C−F, 4JC−F = 2.3 Hz), 142.9, 138.2,
138.1, 132.5, 131.6 (C−F, 3JC−F = 9.0 Hz), 130.6 (C−F, 4JC−F = 4.1
Hz), 128.7, 127.9, 127.7, 125.8 (C−F, 3JC−F = 9.2 Hz), 125.4, 123.5,
122.5, 117.2 (C−F, 2JC−F = 24.2 Hz), 106.9 (C−F, 2JC−F = 23.3 Hz),
72.5, 21.8. HRMS (ESI) m/z: [M + H]+ calcd for C21H17FNO,
318.1289; found, 318.1289.
(m, 2H), 7.65 (td, J = 8.4, 1.2 Hz, 1H), 7.63−7.60 (m, 1H), 7.47 (t, J
= 7.8 Hz, 2H); 13C{1H} NMR (150 MHz, CDCl3): δ 194.8, 157.5,
142.6, 136.2, 133.9, 133.3, 131.2, 130.8, 130.6, 129.1, 128.5, 128.2,
127.8, 127.3, 124.4, 123.8, 122.3, 122.1. HRMS (ESI) m/z: [M + H]+
calcd for C20H14NO, 284.1070; found, 284.1071.
General Procedure for the Synthesis of 3a from 1a and 4a.
Phenylglyoxylic acid (1a, 0.75 mmol), phenanthridin-6-yl(phenyl)-
methanone (4a, 0.25 mmol), and pyridine (6.0 equiv) were added
into an air-tight reaction tube (10 mL) with 2.0 mL of 1,1,2-
trichloroethane. The tube containing the reactants and solvent was
evacuated using a pump and back-filled with high-purified nitrogen
(>99.99%). The reaction mixture was stirred at room temperature
under irradiation with a 3 W LED (420 5 nm) for 10 h. After the
reaction, 1,1,2-trichloroethane was evaporated under reduced
pressure. The resulting crude mixture was purified by flash
chromatography on silica gel (petroleum ether/EtOAc = 7:1) to
provide the desired product 3a (38.5 mg) in 52% yield.
General Procedure for the Reaction of 1a, 2c, and 4a.
Phenylglyoxylic acid (1a, 0.75 mmol), 2-isocyano-4′-methoxy-1,1′-
biphenyl (2c, 0.25 mmol), phenanthridin-6-yl(phenyl)methanone
(4a, 0.25 mmol), and pyridine (6.0 equiv) were added into an air-
tight reaction tube (10 mL) with 2.0 mL of 1,1,2-trichloroethane. The
tube containing the reactants and solvent was evacuated using a pump
and back-filled with high-purified nitrogen (>99.99%). The reaction
mixture was stirred at room temperature under photoirradiation with
a 3 W LED (420
5 nm) for 10 h. After the reaction, volatile
materials were evaporated under reduced pressure. The resulting
crude mixture was purified by flash chromatography on silica gel
(petroleum ether/EtOAc = 9:1) to provide the hydrogenated product
3a (30 mg) and 3x (18 mg) in 42 and 23% yield, respectively, and
produce 4b in 12% yield (9.4 mg).
(8-Methoxyphenanthridin-6-yl)(phenyl)methanone (4b). White
solid; 1H NMR (600 MHz, CDCl3): δ 8.61 (d, J = 9.0 Hz, 1H), 8.56−
8.54 (m, 1H), 8.18−8.17 (m, 1H), 8.05 (d, J = 7.8 Hz, 2H), 7.74−
7.70 (m, 2H), 7.63 (t, J = 7.2 Hz, 1H), 7.53−7.47 (m, 4H), 3.87 (s,
3H); 13C{1H} NMR (150 MHz, CDCl3): δ 194.9, 159.0, 156.1,
141.8, 136.3, 133.9, 130.9, 130.6, 128.5, 128.3, 128.0, 127.8, 125.2,
124.7, 123.9, 122.5, 121.7, 106.6, 55.5. HRMS (ESI) m/z: [M + H]+
calcd for C21H16NO2, 314.1176; found, 314.1175.
(2-Chloro-8-fluorophenanthridin-6-yl)(phenyl)methanol (3ae).
Following the general procedure for the synthesis of 3, the crude
product was purified by silica gel column chromatography (eluent:
hexane/AcOEt = 5:1) to afford a white solid (60.0 mg, 71% yield); 1H
NMR (400 MHz, CDCl3): δ 8.43 (dd, J = 9.2, 5.2 Hz, 1H), 8.38 (d, J
= 2.0 Hz, 1H), 8.15 (d, J = 8.8 Hz, 1H), 7.69 (dd, J = 8.8, 2.4 Hz,
1H), 7.61 (dd, J = 9.6, 2.4 Hz, 1H), 7.48 (td, J = 9.2, 2.4 Hz, 1H),
7.36 (d, J = 6.8 Hz, 2H), 7.32−7.25 (m, 3H), 6.26 (s, 1H), 6.23 (s,
1H); 13C{1H} NMR (100 MHz, CDCl3): δ 161.4 (C−F, 1JC−F
=
249.0 Hz), 158.7, 142.1, 139.8, 133.7, 131.1, 129.4, 129.0, 128.3,
127.7, 125.2 (C−F, 3JC−F = 8.7 Hz), 125.0, 124.9 (C−F, 3JC−F = 8.0
Hz), 121.6, 120.3 (C−F, 2JC−F = 25.0 Hz), 110.9 (C−F, 2JC−F = 21.9
Hz), 72.9. HRMS (ESI) m/z: [M + H]+ calcd for C20H14ClFNO,
338.0742; found, 338.0741.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c01916.
■
sı
(3-Methylphenanthridin-6-yl)(phenyl)methanol (3af). Following
the general procedure for the synthesis of 3, the crude product was
purified by silica gel column chromatography (eluent: hexane/AcOEt
1
= 5:1) to afford a white solid (53.1 mg, 71% yield); H NMR (400
Characterization of EDA complexes, mechanism inves-
1
tigation, and copies of H and 13C NMR spectra of all
MHz, CDCl3): δ 8.53 (d, J = 8.4 Hz, 1H), 8.41 (d, J = 8.4 Hz, 1H),
8.04 (s, 1H), 7.97 (d, J = 8.4 Hz, 1H), 7.71 (t, J = 7.2 Hz, 1H), 7.52−
7.45 (m, 2H), 7.35 (d, J = 7.2 Hz, 2H), 7.28−7.21 (m, 3H), 6.59 (s,
1H), 6.37 (s, 1H), 2.61 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3):
δ 158.9, 143.0, 141.9, 139.2, 133.4, 130.7, 129.1, 129.0, 128.7, 127.9,
127.8, 126.9, 125.9, 123.1, 122.3, 122.1, 121.9, 72.7, 21.5. HRMS
(ESI) m/z: [M + H]+ calcd for C21H18NO, 300.1383; found,
300.1381.
new compounds (PDF)
Crystallographic data of 3a (CIF)
AUTHOR INFORMATION
Corresponding Authors
■
Lei Wang − Advanced Research Institute and Department of
Chemistry, Taizhou University, Taizhou, Zhejiang 318000, P.
R. China; Department of Chemistry; Key Laboratory of Green
and Precise Synthetic Chemistry, Ministry of Education, Huaibei
Normal University, Huaibei, Anhui 235000, P. R. China; State
Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Shanghai 200032, P. R. China;
orcid.org/0000-0001-6580-7671; Email: leiwang88@
hotmail.com
Tao Miao − Department of Chemistry; Key Laboratory of Green
and Precise Synthetic Chemistry, Ministry of Education, Huaibei
Normal University, Huaibei, Anhui 235000, P. R. China; State
Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Shanghai 200032, P. R. China;
Email: taomiao@chnu.edu.cn
(10-Chlorophenanthridin-6-yl)(phenyl)methanol (3ag). Follow-
ing the general procedure for the synthesis of 3, the crude product was
purified by silica gel column chromatography (eluent: hexane/AcOEt
1
= 5:1) to afford a white solid (40.8 mg, 51% yield); H NMR (400
MHz, CDCl3): δ 9.79 (d, J = 8.4 Hz, 1H), 8.27 (dd, J = 8.0, 1.2 Hz,
1H), 7.98 (d, J = 8.0 Hz, 1H), 7.83−7.79 (m, 2H), 7.69 (td, J = 8.8,
1.2 Hz, 1H), 7.39 (t, J = 8.0 Hz, 1H), 7.33 (d, J = 6.8 Hz, 2H), 7.29−
7.22 (m, 3H), 6.46 (d, J = 5.2 Hz, 1H), 6.35 (d, J = 4.8 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3): δ 158.6, 142.7, 134.5, 131.8,
130.4, 129.8, 129.3, 128.8, 128.1, 127.7, 127.1, 126.8, 126.4, 125.9,
125.3, 123.6, 72.9. HRMS (ESI) m/z: [M + H]+ calcd for
C20H15ClNO, 320.0837; found, 320.0835.
Phenanthridin-6-yl(phenyl)methanone (4a). White solid; 1H
NMR (600 MHz, CDCl3): δ 8.70 (d, J = 8.4 Hz, 1H), 8.64 (dd, J
= 5.2, 1.2 Hz, 1H), 8.21 (dd, J = 5.2, 1.2 Hz, 1H), 8.14 (d, J = 8.4 Hz,
1H), 8.04 (dd, J = 8.0, 0.9 Hz, 2H), 7.89−7.86 (m, 1H), 7.79−7.73
H
https://dx.doi.org/10.1021/acs.joc.0c01916
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
Catalysis: A Facile Approach to Ynones. Angew. Chem., Int. Ed.
2015, 54, 8374−8377. (d) Liu, J.; Liu, Q.; Yi, H.; Qin, C.; Bai, R.; Qi,
X.; Lan, Y.; Lei, A. Visible-light-mediated Decarboxylation/Oxidative
Amidation of α-Ketoacids with Amines under Mild Reaction
Conditions Using O2. Angew. Chem., Int. Ed. 2014, 53, 502−506. ,
and references cited therein
(5) (a) Johnstone, R. A. W.; Wilby, A. H.; Entwistle, I. D.
Heterogeneous Catalytic Transfer Hydrogenation and Its Relation to
Other Methods for Reduction of Organic Compounds. Chem. Rev.
1985, 85, 129−170. (b) Smith, M. March’s Advanced Organic
Chemistry: Reactions, Mechanisms, and Structure; Wiley: Hoboken,
2006; pp 1703−1869. (c) The Handbook of Homogeneous Hydro-
genation; Elsevier, C. J., De Vries, J. G., Eds.; Wiley-VCH: Weinheim,
Authors
Wei Shi − Advanced Research Institute and Department of
Chemistry, Taizhou University, Taizhou, Zhejiang 318000, P.
R. China; Department of Chemistry; Key Laboratory of Green
and Precise Synthetic Chemistry, Ministry of Education, Huaibei
Normal University, Huaibei, Anhui 235000, P. R. China
Fang Ma − Department of Chemistry; Key Laboratory of Green
and Precise Synthetic Chemistry, Ministry of Education, Huaibei
Normal University, Huaibei, Anhui 235000, P. R. China;
orcid.org/0000-0001-7178-7232
Pinhua Li − Department of Chemistry; Key Laboratory of Green
and Precise Synthetic Chemistry, Ministry of Education, Huaibei
Normal University, Huaibei, Anhui 235000, P. R. China; State
Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Shanghai 200032, P. R. China;
orcid.org/0000-0002-8528-8087
̈
2007. (d) Samec, J. S. M.; Backvall, J.-E.; Andersson, P. G.; Brandt, P.
Mechanistic Aspects of Transition Metal-Catalyzed Hydrogen Trans-
fer Reactions. Chem. Soc. Rev. 2006, 35, 237−248.
(6) For selected reviews, see: (a) Foster, R. Electron Donor-
Acceptor Complexes. J. Phys. Chem. 1980, 84, 2135−2141.
(b) Rosokha, S. V.; Kochi, J. K. Fresh Look at Electron-Transfer
Mechanisms via the Donor/Acceptor Bindings in the Critical
Encounter Complex. Acc. Chem. Res. 2008, 41, 641−653. (c) Lima,
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c01916
C. G. S.; de M Lima, T.; Duarte, M.; Jurberg, I. D.; Paixao, M. W.
̃
Notes
Organic Synthesis Enabled by Light-Irradiation of EDA Complexes:
Theoretical Background and Synthetic Applications. ACS Catal. 2016,
6, 1389−1407. (d) Crisenza, G. E. M.; Mazzarella, D.; Melchiorre, P.
Synthetic Methods Driven by the Photoactivity of Electron Donor-
Acceptor Complexes. J. Am. Chem. Soc. 2020, 142, 5461−5476.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was financially supported by the National Natural
Science Foundation of China (21772062, 22071171, and
21602072) and the National Science Foundation of Anhui
Education Department (KJ2019ZD66 and KJ2017A388).
́
́
(7) (a) Arceo, E.; Jurberg, I. D.; Alvarez-Fernandez, A.; Melchiorre,
P. Photochemical Activity of a Key Donor-Acceptor Complex can
Drive Stereoselective Catalytic α-Alkylation of Aldehydes. Nat. Chem.
2013, 5, 750−756. (b) Silvi, M.; Arceo, E.; Jurberg, I. D.; Cassani, C.;
Melchiorre, P. Enantioselective Organocatalytic Alkylation of
Aldehydes and Enals Driven by the Direct Photoexcitation of
Enamines. J. Am. Chem. Soc. 2015, 137, 6120−6123. (c) Bahamonde,
A.; Melchiorre, P. Mechanism of the Stereoselective α-Alkylation of
Aldehydes Driven by the Photochemical Activity of Enamines. J. Am.
Chem. Soc. 2016, 138, 8019−8030. (d) Cao, Z.-Y.; Ghosh, T.;
Melchiorre, P. Enantioselective Radical Conjugate Additions Driven
by a Photoactive Intramolecular Iminium-ion-based EDA Complex.
Nat. Commun. 2018, 9, 3274.
REFERENCES
■
(1) (a) Penteado, F.; Lopes, E. F.; Alves, D.; Perin, G.; Jacob, R. G.;
Lenardao
̃
, E. J. α-Keto Acids: Acylating Agents in Organic Synthesis.
Chem. Rev. 2019, 119, 7113−7278. (b) Xu, W.-T.; Huang, B.; Dai, J.-
J.; Xu, J.; Xu, H.-J. Catalyst-free Singlet Oxygen-promoted
Decarboxylative Amidation of α-Keto Acids with Free Amines. Org.
Lett. 2016, 18, 3114−3117. (c) Wei, Y.; Hu, P.; Zhang, M.; Su, W.
Metal-catalyzed Decarboxylative C-H Functionalization. Chem. Rev.
2017, 117, 8864−8907. (d) Collet, F.; Song, B.; Rudolphi, F.;
Gooßen, L. J. Development of Decarboxylative Coupling Processes
for the Synthesis of Azomethines and Ketones. Eur. J. Org. Chem.
2011, 2011, 6486−6501.
(2) (a) Gooßen, L. J.; Rudolphi, F.; Oppel, C.; Rodríguez, N.
Synthesis of Ketones from α-Oxocarboxylates and Aryl Bromides by
Cu/Pd-catalyzed Decarboxylative Cross-coupling. Angew. Chem., Int.
Ed. 2008, 47, 3043−3045. (b) Fang, P.; Li, M.; Ge, H. Room
Temperature Palladium-Catalyzed Decarboxylative ortho-Acylation of
Acetanilides with α-Oxocarboxylic Acids. J. Am. Chem. Soc. 2010, 132,
11898−11899. (c) Wang, H.; Guo, L.-N.; Duan, X.-H. Decarbox-
ylative Acylation of Cyclic Enamides with α-Oxocarboxylic Acids by
Palladium-Catalyzed C-H Activation at Room Temperature. Org. Lett.
2012, 14, 4358−4361. (d) Li, H.; Li, P.; Zhao, Q.; Wang, L.
Unprecedented ortho-Acylation of Azoxybenzenes with α-Oxocarbox-
ylic Acids by Pd-Catalyzed C−H Activation and Decarboxylation.
Chem. Commun. 2013, 49, 9170−9172. , and references cited therein
(3) Liu, J.; Fan, C.; Yin, H.; Qin, C.; Zhang, G.; Zhang, X.; Yi, H.;
Lei, A. Synthesis of 6-Acyl Phenanthridines by Oxidative Radical
Decarboxylation-Cyclization of α-Oxocarboxylates and Isocyanides.
Chem. Commun. 2014, 50, 2145−2147.
(8) (a) Nappi, M.; Bergonzini, G.; Melchiorre, P. Metal-Free
Photochemical Aromatic Perfluoroalkylation of α-Cyanoarylacetates.
Angew. Chem., Int. Ed. 2014, 53, 4921−4925. (b) Liu, Y.; Chen, X.-L.;
Sun, K.; Li, X.-Y.; Zeng, F.-L.; Liu, X.-C.; Qu, L.-B.; Zhao, Y.-F.; Yu,
B. Visible-Light Induced Radical Perfluoroalkylation/Cyclization
Strategy to Access 2-Perfluoroalkyl Benzothiazoles/Benzoselenazoles
by EDA complex. Org. Lett. 2019, 21, 4019−4024. (c) Jiang, H.; He,
Y.; Cheng, Y.; Yu, S. Radical Alkynyltrifluoromethylation of Alkenes
Initiated by an Electron Donor-Acceptor Complex. Org. Lett. 2017,
19, 1240−1243. (d) Cheng, Y.; Yuan, X.; Ma, J.; Yu, S. Direct
Aromatic C-H Trifluoromethylation via an Electron-Donor-Acceptor
Complex. Chem.Eur. J. 2015, 21, 8355−8359.
(9) (a) Zhu, M.; Zhou, K.; Zhang, X.; You, S.-L. Visible-Light-
Promoted Cascade Alkene Trifluoromethylation and Dearomatization
of Indole Derivatives via Intermolecular Charge Transfer. Org. Lett.
2018, 20, 4379−4383. (b) Ghosh, S.; Kumar, G.; Naveen, N.;
Pradhan, S.; Chatterjee, I. EDA Complex Directed N-Centred Radical
Generation from Nitrosoarenes: A Divergent Synthetic Approach.
Chem. Commun. 2019, 55, 13590−13593.
(10) (a) Yang, M.; Cao, T.; Xu, T.; Liao, S. Visible-Light-Induced
Deaminative Thioesterification of Amino Acid Derived Katritzkysalts
via Electron Donor-Acceptor Complex Formation. Org. Lett. 2019, 21,
8673−8678. (b) Zhang, J.; Li, Y.; Xu, R.; Chen, Y. Donor-Acceptor
Complex Enables Alkoxylradical Generation for Metal-Free C(sp3)-
C(sp3) Cleavage and Allylation/Alkenylation. Angew. Chem., Int. Ed.
2017, 56, 12619−12623. (c) Liu, J.-L.; Zhu, Z.-F.; Liu, F.
Oxycyanation of Vinyl Ethers with 2,2,6,6-Tetramethyl-N-oxopiper-
idinium Enabled by Electron Donor-Acceptor Complex. Org. Lett.
2018, 20, 720−723. (d) Kandukuri, S. R.; Bahamonde, A.; Chatterjee,
(4) (a) Wang, G.-Z.; Shang, R.; Cheng, W.-M.; Fu, Y.
Decarboxylative 1,4-Addition of α-Oxocarboxylic Acids with Michael
Acceptors Enabled by Photoredox Catalysis. Org. Lett. 2015, 17,
4830−4833. (b) Chu, L.; Lipshultz, J. M.; MacMillan, D. W. C.
Merging Photoredox and Nickel Catalysis: The Direct Synthesis of
Ketones by the Decarboxylative Arylation of α-Oxo Acids. Angew.
Chem., Int. Ed. 2015, 54, 7929−7933. (c) Tan, H.; Li, H.; Ji, W.;
Wang, L. Sunlight-Driven Decarboxylative Alkynylation of α-Keto
Acids with Bromoacetylenes by Hypervalent Iodine Reagent
I
https://dx.doi.org/10.1021/acs.joc.0c01916
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
́
I.; Jurberg, I. D.; Escudero-Adan, E. C.; Melchiorre, P. X-Ray
Characterization of an Electron Donor-Acceptor Complex that Drives
the Photochemical Alkylation of Indoles. Angew. Chem., Int. Ed. 2015,
54, 1485−1489. (e) Li, Y.; Miao, T.; Li, P.; Wang, L. Photo-Driven
Synthesis of C6-Polyfunctionalized Phenanthridines from Three-
component Reactions of Isocyanides, Alkynes, and Sulfinic Acids by
Electron Donor-Acceptor Complex. Org. Lett. 2018, 20, 1735−1739.
(f) Li, Y.; Ma, F.; Li, P.; Miao, T.; Wang, L. Hydrogen and Sulfonyl
Radical Generation for the Hydrogenation and Arylsulfonylation of
Alkenes Driven by Photochemical Activity of Hydrogen Bond Donor-
Acceptor Complexes. Adv. Synth. Catal. 2019, 361, 1606−1616.
(g) Lygin, A. V.; de Meijere, A. Isocyanides in the Synthesis of
Nitrogen Heterocycles. Angew. Chem., Int. Ed. 2010, 49, 9094−9124.
(h) Qiu, G.; Ding, Q.; Wu, J. Recent Advances in Isocyanide Insertion
Chemistry. Chem. Soc. Rev. 2013, 42, 5257−5269. (i) Song, B.; Xu, B.
Metal-Catalyzed C−H Functionalization Involving Isocyanides. Chem.
Soc. Rev. 2017, 46, 1103−1123. (j) Zhang, B.; Studer, A. Recent
Advances in the Synthesis of Nitrogen Heterocycles via Radical
Cascade Reactions UsingIsonitriles as Radical Acceptors. Chem. Soc.
Rev. 2015, 44, 3505−3521.
(11) Benesi, H. A.; Hildebrand, J. H. A Spectrophotometric
Investigation of the Interaction of Iodine with Aromatic Hydro-
carbons. J. Am. Chem. Soc. 1949, 71, 2703−2707.
(12) (a) Furukawa, K.; Inada, H.; Shibuya, M.; Yamamoto, Y.
Chemoselective Conversion from α-Hydroxy Acids to α-Keto Acids
Enabled by Nitroxyl-Radical-Catalyzed Aerobic Oxidation. Org. Lett.
2016, 18, 4230−4233. (b) Crich, D.; Zou, Y. Catalytic Oxidation
Adjacent to Carbonyl Groups and at Benzylic Positions with a
Fluorous Seleninic Acid in the Presence of Iodoxybenzene. J. Org.
Chem. 2005, 70, 3309−3311.
(13) (a) Zhang, B.; Muck-Lichtenfeld, C.; Daniliuc, C. G.; Studer, A.
̈
6-Trifluoromethylphenanthridines through Radical Trifluoromethyla-
tion of Isonitriles. Angew. Chem., Int. Ed. 2013, 52, 10792−10795.
(b) Kobiki, Y.; Kawaguchi, S.-i.; Ogawa, A. Palladium-Catalyzed
Synthesis of α-Diimines from Triarylbismuthines and Isocyanides.
Org. Lett. 2015, 17, 3490−3493.
J
https://dx.doi.org/10.1021/acs.joc.0c01916
J. Org. Chem. XXXX, XXX, XXX−XXX