Cyanomethylation and Cyclization of Aryl Alkynoates with Acetonitrile under Transition-Metal-Free Conditions: Synthesis of 3-Cyanomethylated Coumarins

Article abstract of DOI:10.1021/acs.joc.6b02155

Cyanomethylated coumarins were synthesized via cyanomethylation and cyclization of aryl alkynoates using cheap and available reagent acetonitrile as the cyanomethyl source in the presence of TBPB (tert-butyl peroxybenzoate) under transition-metal-free con

Full text of DOI:10.1021/acs.joc.6b02155

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Note
Cyanomethylation and Cyclization of Aryl Alkynoates with Acetonitrile under
Transition Metal-free Conditions: Synthesis of 3-Cyanomethylated Coumarins
Yulan Yu, Shengyi Zhuang, Ping Liu, and Peipei Sun
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b02155 • Publication Date (Web): 21 Oct 2016
Downloaded from http://pubs.acs.org on October 21, 2016
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Cyanomethylation and Cyclization of Aryl Alkynoates with
Acetonitrile under Transition Metal-free Conditions: Synthesis of
3-Cyanomethylated Coumarins
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Yulan Yu, Shengyi Zhuang, Ping Liu and Peipei Sun*
College of Chemistry and Materials Science, Jiangsu Provincial Key Laboratory of Material Cycle
Processes and Pollution Control, Jiangsu Collaborative Innovation Center of Biomedical
Functional Materials, Nanjing Normal University, Nanjing 210023, China
sunpeipei@njnu.edu.cn
ABSTRACT: Cyanomethylated coumarins were synthesized via cyanomethylation and
cyclization of aryl alkynoates using cheap and available reagent acetonitrile as the cyanomethyl
source in the presence of TBPB (tertꢀbutyl peroxybenzoate) under transition metalꢀfree conditions.
For the substrates with various substituents on benzene ring, the reaction proceeded smoothly to
give the corresponding products in moderate to good yields. The resulting products could be
simply converted into some other related coumarin derivatives.
Cyano group exists in a number of natural products and pharmaceuticals.1 It is also an important
structural motif in organic synthesis because this group can be easily converted into other
functional groups such as carboxylic acids, esters, amides, amines, aldehydes, tetrazoles and
ketones.2 In addition, the C–CN bond activation provided new chances for the synthesis of various
functional molecules.3 Thus, many efforts have been paid for the preparation of nitriles. Except
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virulent potassium cyanide or sodium cyanide, several compounds such as TMSCN,4
Nꢀcyanosuccinimide,5 NꢀcyanoꢀNꢀphenylꢀpꢀmethylbenzenesulfonamide (NCTS),6 etc. were
employed as the cyano sources. What is more, a series of cyanation methods were developed by
using inert acetonitrile as the cyanating reagent via C–CN bond cleavage.7 Except the direct
cyanation, cyanoalkylation provided another synthetically useful protocol for the synthesis of
nitriles.8 As a cheap and available cyanoꢀcontaining compound, the synthetic use of acetonitrile
via the methyl C (sp3)–H bond activation has been aroused much attention in recent years.
Specially, the cyanomethylation of activated alkenes have been well studied, and a cyanomethyl
radical was believed to be involved in these tandem reaction processes.9 It will be valuable to
further develop the application of this reagent in the synthesis of the useful cyanoꢀcontaining
compounds from the viewpoint of perfect atom economy.
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The addition of radicals to carbon–carbon triple bond can form the highly reactive vinyl
radicals. The sequential additions of these vinyl radicals to other πꢀsystems provide the
opportunity to construct new carbon–carbon bond, especially to produce cyclic compounds. By
this strategy, a series of coumarin derivatives, a class of very important heterocyclic compounds in
pharmaceuticals as well as in fluorescent materials,10 were synthesized via the addition of several
radicals to aryl alkynoates, in which diselenides,11 Togni’s reagent (trifluoromethylation
reagent),12 dialkyl Hꢀphosphonates,13 sulfonylhydrazides,14 sulfinic acids,15 αꢀketo acids,16 ethyl
bromodifluoroacetate,17 NIS18 and 2,4ꢀdiones19 were employed as the radical sources. As the
continuous study of our group on the covalent bond activation of inert solvents and their
application in organic synthesis,20 in this work, we selected acetonitrile as the cyanomethyl source,
through a peroxide promoted C–H bond activation and addition to carbon–carbon triple bond of
aryl alkynoates, followed by cyclization to synthesize 3ꢀcyanomethylated coumarins.
In our initial study, phenyl 3ꢀphenylpropiolate (1a) was chosen as a model substrate to react
with acetonitrile for the optimization of reaction conditions (Table 1). We were pleased to find that
peroxide could obviously promote the transformation. In the presence of 1 equiv TBPB (tertꢀbutyl
peroxybenzoate) and without any transitionꢀmetal catalyst, a cyanomethylated and cyclized
product 2ꢀ(2ꢀoxoꢀ4ꢀphenylꢀ2Hꢀchromenꢀ3ꢀyl)acetonitrile (2a) was obtained in 30% yield at 120
oC under N2 atmosphere after 16 h (entry 1). Increasing TBPB to 2.0 equiv resulted in a higher
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yield of 45% (entry 2); while the addition of 3.0 equiv TBPB did not further improve the yield of
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the product (entry 3). Several other peroxides such as DTBP (diꢀtertꢀbutyl peroxide), TBHP
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(tertꢀbutyl hydroperoxide), BPO (benzoyl peroxide) and DCP (dicumyl peroxide) were then
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9
screened, and all of them showed very low efficiency for this reaction (entries 4ꢀ7). Rising the
reaction temperature to 130 oC enhanced the yield to 62%, but at 100 oC, only a low yield of 16%
was obtained (entries 8, 9). The presence of base was proved to be beneficial for the reaction.
Thus, a series of bases were tested, and Na2CO3 gave the best result (entries 10ꢀ14). When 2 equiv
Na2CO3 was added, the yield of 2a could be increased to 83% (entry 14). In addition, if the
reaction took place in air atmosphere, there was a little decrease with the yield (entry 15).
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Table 1. Optimization of Reaction Conditionsa
entry
1
oxidant (equiv)
TBPB (1)
TBPB (2)
TBPB (3)
DTBP (2)
TBHP (2)
BPO (2)
base (equiv)
temperature (oC)
yield (%)
30
120
120
120
120
120
120
120
130
100
130
130
130
130
--
2
45
--
3
42
--
4
ꢀꢀ
<5
5
--
<5
6
ꢀꢀ
12
7
DCP (2)
ꢀꢀ
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8
TBPB (2)
TBPB (2)
TBPB (2)
TBPB (2)
TBPB (2)
TBPB (2)
ꢀꢀ
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9
ꢀꢀ
16
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13
KOAc (2)
K2HPO4 (2)
NaHCO3 (2)
Na2CO3 (2)
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73
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TBPB (2)
TBPB (2)
NaOH (2)
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130
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78
15b
Na2CO3 (2)
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aUnless otherwise specified, the reactions were carried out in the presence of 1a (0.3 mmol),
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oxidant, base and CH3CN (2 mL) under N2 atmosphere for 16 h. bIn air atmosphere.
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With the optimized conditions in hand, we then examined the reaction of various alkynoates
with CH3CN (Table 2). Aryl phenylpropiolates with a variety of substituents on the aromatic ring
(phenoxy ring) were firstly employed as the reactants. It was interesting that the ester migration
might occur in these reaction processes and the position of C–O bond in the products was not
the same as that in the substrates, which was consistent with the previous related reports.16b,18,19
For example, when the substrates with a substituent on the paraꢀposition of the phenoxy ring were
used, the 7ꢀposition substituted coumarin derivatives were obtained (2bꢀ2l). The reactions of the
substrates with electronꢀdonating groups such as alkyl, alkoxy or phenyl on the aromatic rings
gave moderate to good yields (2bꢀ2h), and the presence of electronꢀwithdrawing groups such as
halogen or trifluoromethyl led to a little decrease of the yields (2iꢀ2l). A 3,5ꢀdimethyl substituted
substrate (1m) also gave the corresponding product (2m) in 79% yield. For the metaꢀchloro
substituted reactant (1n), a mixture of the products 2n1 and 2n2 was separated from the reaction
mixture in a ratio of 2:1. However, from oꢀtolyl phenylpropiolate (1p), we almost did not obtain
the desired product, which was obviously due to the steric hindrance. We next investigated the
influence of the substituent directly bonded to the carbon−carbon triple bond. As that were shown
in Table 2, alkynes having either an electronꢀdeficient or electronꢀrich aromatic ring gave the
corresponding coumarins in moderate yields (2q-2z), and the electronic effect of the substituent
here was not evident. When an alkyl group directly bonded to the carbon−carbon triple bond,
however, no desired coumarin derivative (2aa) was obtained.
Table 2. Cyclization of Various Alkynoates with Acetonitrilea
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2b, 82%
2a, 83%
2c, 78%
2d, 70%
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Ph
O
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CN
Ph
O
2f, 76%
2j, 70%
2g, 70%
2k, 68%
2h, 72%
2e, 73%
2i, 65%
2l, 65%
2o, 76%
2m, 79%
2n1+2n2, 72% (2:1)
2q, 55%
2p, trace
2r, 64%
2s, 60%
2w, 63%
2v, 62%
2u, 65%
2t, 68%
2z, 63%
2x, 50%
2aa, 0%
2y, 64%
aReaction conditions: 1 (0.3 mmol), TBPB (2 equiv), Na2CO3 (2 equiv) in CH3CN (2 mL) at 130
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oC under N2 atmosphere for 16 h.
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The structures of 2h and 2u were further confirmed by single crystal Xꢀray diffraction
analysis (See Supporting Information).21
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We further explored the scope of this tandem cyclization by using acetone instead of
acetonitrile. Under the same reaction conditions, 3ꢀ(2ꢀoxopropyl) substituted coumarins 3 were
obtained in satisfied yields (Scheme 1).
Scheme 1. Cyclization of Alkynoates with Acetone
3k, 70%
3a, 68%
3c, 74%
3e, 78%
As mentioned before, the cyano group is an important motif which can be converted into
various functional groups. We then decided to use this intramolecular cyclization in the synthesis
of other functionalized coumarins by the conversion of cyano group (Scheme 2). Firstly,
dissolving the cyanomethylated product 2ꢀ(2ꢀoxoꢀ4ꢀphenylꢀ2Hꢀchromenꢀ3ꢀyl)acetonitrile (2a) in
methanol, in the presence of H2SO4, 2a could be converted into methyl
2ꢀ(2ꢀoxoꢀ4ꢀphenylꢀ2Hꢀchromenꢀ3ꢀyl)acetate (4a) after heating the mixture for 24 h. In addition,
2a could be easily hydrolyzed to generate 2ꢀ(2ꢀoxoꢀ4ꢀphenylꢀ2Hꢀchromenꢀ3ꢀyl)acetamide (5a) in
the presence of H2O2 and K2CO3.
Scheme 2. Transformation of Cyanomethylated Coumarin
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In order to understand the details of the reaction mechanism, some control experiments were
carried out, as shown in Scheme 3. The reaction was completely inhibited when 4 equiv radical
scavenger
TEMPO
(2,2,6,6ꢀtetramethylꢀ1ꢀpiperidinyloxy)
or
BHT
(2,6ꢀdiꢀtertꢀbutylꢀ4ꢀmethylphenol) was added under the standard reaction conditions. These results
indicated that this reaction might proceed via a radical pathway.
Scheme 3. Control Experiments
Based on the above results and the previous related reports,11ꢀ19 a possible reaction
mechanism was proposed in Scheme 4. Initially, TBPB decomposed into tertꢀbutoxy and
benzoyloxy radical at high temperature. These radicals abstracted a hydrogen radical from CH3CN
to generate the cyanomethyl radical which added to alkynoate (1b) to produce the alkenyl radical
A. The radical intermediate A underwent an intramolecular spirocyclization to give the
spiroꢀradical intermediate B. The ester migration then took place via a carboxyl radical C to
generate the coumarin radical D. D was finally oxidized to a carbocation followed by
deprotonation to yield the product 2b.
Scheme 4. Plausible Reaction Mechanism
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In summary, we have developed a novel tandem oxidative cyclization reaction for the
preparation of cyanomethylated coumarins using cheap and available acetonitrile as the
cyanomethyl source by means of metalꢀfree catalysis. The reaction was found to tolerate a wide
range of functional groups. Furthermore, as an important precursor, cyano group can be converted
into various functional groups. The convenient and efficient pathway for the synthesis of
functionalized coumarins will have important values in synthetic and pharmaceutical chemistry.
Experimental Section
General.
All reactions were run in a sealed tube with a Teflon lined cap under ambient N2. Chemicals were
commercially available from chemical suppliers and were used without purification. Solvents
were dried in a standard way. Aryl phenylpropiolates were prepared according to the literature
procedures.22 The NMR spectra were recorded at 400 MHz (1H) and 100 MHz (13C) in CDCl3 or
DMSOꢀd6 using TMS as an internal standard. The following abbreviations were used to explain
the multiplicities: s = singlet, d = doublet, dd = doublet of doublet, t = triplet, dt = doublet of
triplet, td = triplet of doublet, q = quartet, m = multiplet, ddd = doublet of doublet of doublet.
Melting points are uncorrected. QꢀTOF was used for the HRMS measurements.
General experimental procedure for the synthesis of cyanomethylated coumarins. Aryl
alkynoate (1) (0.3 mmol), Na2CO3 (0.6 mmol), TBPB (0.6 mmol) were added in CH3CN (2 mL)
under N2 atmosphere. The solution was stirred at 130 oC for 16 h. After completion of the reaction,
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the resulting solution was cooled to room temperature and diluted with EtOAc (15 mL), then
washed with brine. The organic layer was dried over anhydrous Mg2SO4, filtered and concentrated
in vacuo. The residue was purified by silica gel chromatography using hexane/ethyl acetate (5:1)
to afford the pure product (2).
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3ꢀ(2ꢀOxopropyl) substituted coumarins (3a, 3c, 3e and 3k) were synthesized using the same
procedures in acetone.
Preparation of methyl 2-(2-oxo-4-phenyl-2H-chromen-3-yl)acetate (4a). To a solution of
2ꢀ(2ꢀoxoꢀ4ꢀphenylꢀ2Hꢀchromenꢀ3ꢀyl)acetonitrile (2a, 130.5 mg, 0.5 mmol) in MeOH (4 mL) in a
sealed tube was added H2O (4 drops) and H2SO4 (conc., 1.5 mL). The reaction mixture was heated
o
at 90 C for 24 h. After cooling to room temperature, the reaction mixture was slowly quenched
with saturated aqueous NaHCO3 to pH 8 and extracted with DCM (10 mL × 3). The combined
organic phases were washed with brine (15 mL), dried over anhydrous Na2SO4, and concentrated
in vacuo. The residue was purified by silica gel chromatography using hexane/ethyl acetate (5:1)
to afford the pure product 4a.
Preparation of 2-(2-oxo-4-phenyl-2H-chromen-3-yl)acetamide (5a). To a stirred solution of
2ꢀ(2ꢀoxoꢀ4ꢀphenylꢀ2Hꢀchromenꢀ3ꢀyl)acetonitrile (2a, 130.5 mg, 0.5 mmol) in DMSO (2 mL) was
added 30% H2O2 (0.5 mL) and K2CO3 (69.1 mg, 0.5 mmol) at 0 oC. Then the reaction mixture was
stirred at room temperature for 0.5 h. After completion of the reaction, the reaction mixture was
diluted with H2O (15 mL) and extracted with EtOAc (15 mL × 3). The combined organic phases
were washed with brine (15 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo.
The residue was purified by silica gel chromatography using hexane/ethyl acetate (5:1) to afford
the pure product 5a.
2-(2-Oxo-4-phenyl-2H-chromen-3-yl)acetonitrile (2a). Yellow solid (65.0 mg, 83% yield); mp
134–135 oC; 1H NMR (400 MHz, CDCl3) δ 7.63–7.57 (m, 4H), 7.43 (d, J = 8.2 Hz, 1H), 7.35 (dd,
J = 7.6, 1.6 Hz, 2H), 7.25–7.21 (m, 1H), 7.10 (dd, J = 8.0, 1.4 Hz, 1H), 3.45 (s, 2H); 13C NMR
(100 MHz, CDCl3) δ 160.3, 154.6, 153.1, 132.9, 132.5, 129.9, 129.5, 128.0, 124.7, 119.8, 117.0,
116.4, 116.3, 17.5; HRMS (ESI) m/z calcd for C17H12NO2 [M + H]+ 262.0863, found 262.0865.
2-(7-Methyl-2-oxo-4-phenyl-2H-chromen-3-yl)acetonitrile (2b). Yellow solid (67.7 mg, 82%
o
1
yield); mp 98–100 C; H NMR (400 MHz, CDCl3) δ 7.64–7.58 (m, 3H), 7.34–7.32 (m, 2H),
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7.23 (s, 1H), 7.04–7.02 (m, 1H), 6.97 (d, J = 8.1 Hz, 1H), 3.42 (s, 2H), 2.47 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 160.6, 154.6, 153.1, 144.0, 133.1, 129.7, 129.4, 128.0, 127.6, 125.9, 117.4,
117.1, 116.6, 115.0, 21.7, 17.4; HRMS (ESI) m/z calcd for C18H14NO2 [M + H]+ 276.1019, found
276.1020.
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2-(7-Ethyl-2-oxo-4-phenyl-2H-chromen-3-yl)acetonitrile (2c). Yellow solid (67.6 mg, 78% yield);
mp 75–77 oC; 1H NMR (400 MHz, CDCl3) δ 7.64–7.56 (m, 3H), 7.35–7.32 (m, 2H), 7.26 (d, J =
1.2 Hz, 1H), 7.06 (dd, J = 8.2, 1.6 Hz, 1H), 7.00 (d, J = 8.2 Hz, 1H), 3.43 (s, 2H), 2.76 (q, J = 7.6
Hz, 2H), 1.28 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 160.6, 154.6, 153.3, 150.2, 133.1,
129.7, 129.4, 128.0, 127.8, 124.7, 117.6, 116.6, 115.9, 115.0, 28.9, 17.5, 15.1; HRMS (ESI) m/z
calcd for C19H16NO2 [M + H]+ 290.1176, found 290.1173.
2-(7-Isopropyl-2-oxo-4-phenyl-2H-chromen-3-yl)acetonitrile (2d). Yellow oil (63.7 mg, 70%
yield); 1H NMR (400 MHz, CDCl3) δ 7.64–7.58 (m, 3H), 7.35–7.33 (m, 2H), 7.29 (d, J = 1.6 Hz,
1H), 7.10 (dd, J = 8.3, 1.7 Hz, 1H), 7.01 (d, J = 8.2 Hz, 1H), 3.43 (s, 2H), 3.05–2.98 (m, 1H), 1.29
(d, J = 6.9 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 160.6, 154.9, 154.6, 153.3, 133.1, 129.7, 129.4,
128.0, 127.8, 123.4, 117.7, 116.6, 115.0, 114.6, 34.2, 23.6, 17.4; HRMS (ESI) m/z calcd for
C20H18NO2 [M + H]+ 304.1332, found 304.1334.
2-(7-tert-Butyl-2-oxo-4-phenyl-2H-chromen-3-yl)acetonitrile (2e). Yellow oil (69.5 mg, 73%
1
yield); H NMR (400 MHz, CDCl3) δ 7.63–7.56 (m, 3H), 7.43 (d, J = 1.8 Hz, 1H), 7.34 (dd, J =
7.8, 1.7 Hz, 2H), 7.26 (dd, J = 8.5, 1.9 Hz, 1H), 7.03 (d, J = 8.4 Hz, 1H), 3.44 (s, 2H), 1.36 (s, 9H);
13C NMR (100 MHz, CDCl3) δ 160.6, 157.2, 154.5, 153.1, 133.1, 129.8, 129.4, 128.0, 127.5,
122.3, 117.4, 116.6, 115.2, 113.7, 35.3, 31.0, 17.4; HRMS (ESI) m/z calcd for C21H20NO2 [M +
H]+ 318.1489, found 318.1492.
2-(7-Methoxy-2-oxo-4-phenyl-2H-chromen-3-yl)acetonitrile (2f). Yellow oil (66.4 mg, 76% yield);
1H NMR (400 MHz, CDCl3) δ 7.63–7.57 (m, 3H), 7.33 (dd, J = 7.8, 1.7 Hz, 2H), 6.99 (d, J = 8.9
Hz, 1H), 6.91 (d, J = 2.5 Hz, 1H), 6.78 (dd, J = 8.9, 2.5 Hz, 1H), 3.90 (s, 3H), 3.40 (s, 2H); 13C
NMR (100 MHz, CDCl3) δ 163.3, 160.7, 154.9, 154.7, 133.2, 129.7, 129.4, 128.9, 127.9, 116.7,
113.4, 112.9, 112.7, 100.8, 55.9, 17.3; HRMS (ESI) m/z calcd for C18H14NO3 [M + H]+ 292.0968,
found 292.0966.
2-(2-Oxo-7-phenoxy-4-phenyl-2H-chromen-3-yl)acetonitrile (2g). Yellow oil (74.2 mg, 70% yield);
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1H NMR (400 MHz, CDCl3) δ 7.69–7.54 (m, 3H), 7.48–7.40 (m, 2H), 7.34 (dd, J = 7.7, 1.7 Hz,
2H), 7.27–7.23 (m, 1H), 7.10 (dd, J = 8.6, 1.0 Hz, 2H), 7.03 (d, J = 8.9 Hz, 1H), 6.92 (d, J = 2.4
Hz, 1H), 6.85 (dd, J = 8.9, 2.4 Hz, 1H), 3.41 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 161.9, 160.4,
154.8, 154.5, 133.0, 130.3, 129.8, 129.5, 129.3, 127.9, 125.3, 120.4, 116.6, 114.8, 114.6, 113.6,
104.9, 17.4; HRMS (ESI) m/z calcd for C23H16NO3 [M + H]+ 354.1125, found 354.1125.
2-(2-Oxo-4,7-diphenyl-2H-chromen-3-yl)acetonitrile (2h). Yellow solid (72.8 mg, 72% yield); mp
133–135 oC; 1H NMR (400 MHz, CDCl3) δ 7.68–7.62 (m, 6H), 7.53–7.45 (m, 4H), 7.38 (dd, J =
7.8, 1.6 Hz, 2H), 7.17 (d, J = 8.3 Hz, 1H), 3.47 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 160.5,
154.4, 153.4, 145.6, 138.7, 132.9, 129.9, 129.5, 129.2, 128.8, 128.3, 128.0, 127.2, 123.5, 118.7,
116.5, 115.8, 115.0, 17.6; HRMS (ESI) m/z calcd for C23H16NO2 [M+H]+ 338.1176, found
338.1178.
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2-(7-Fluoro-2-oxo-4-phenyl-2H-chromen-3-yl)acetonitrile (2i). Yellow solid (54.4 mg, 65% yield);
mp 159–160 oC; 1H NMR (400 MHz, CDCl3) δ 7.65–7.58 (m, 3H), 7.33 (dd, J = 7.7, 1.7 Hz, 2H),
7.15–7.08 (m, 2H), 6.98–6.93 (m, 1H), 3.42 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 164.6 (d, J =
256.6 Hz), 160.0, 154.2 (d, J = 13.0 Hz), 154.2 (d, J = 1.0 Hz), 132.7, 130.1, 130.0 (d, J = 10.3
Hz), 129.9, 129.6, 127.9, 116.6 (d, J = 2.8 Hz), 116.3, 115.2 (d, J = 3.0 Hz), 112.8 (d, J = 22.6 Hz),
104.5 (d, J = 25.8 Hz), 17.5; HRMS (ESI) m/z calcd for C17H11FNO2 [M + H]+ 280.0768, found
280.0771.
2-(7-Chloro-2-oxo-4-phenyl-2H-chromen-3-yl)acetonitrile (2j). Yellow solid (62.0 mg, 70%
yield); mp 140–141 oC; 1H NMR (400 MHz, CDCl3) δ 7.66–7.60 (m, 3H), 7.42 (d, J = 1.9 Hz, 1H),
7.34–7.32 (m, 2H), 7.19 (dd, J = 8.6, 2.0 Hz, 1H), 7.05 (d, J = 19.5 Hz, 1H), 3.43 (s, 2H); 13C
NMR (100 MHz, CDCl3) δ 159.7, 154.0, 153.2, 138.5, 132.5, 130.1, 129.6, 128.9, 127.9, 125.3,
118.5, 117.2, 116.3, 116.2, 17.5; HRMS (ESI) m/z calcd for C17H11ClNO2 [M + H]+ 296.0473,
found 296.0472.
2-(7-Bromo-2-oxo-4-phenyl-2H-chromen-3-yl)acetonitrile (2k). Yellow solid (69.2 mg, 68%
yield); mp 105–107 oC; 1H NMR (400 MHz, CDCl3) δ 7.65–7.59 (m, 4H), 7.36ꢀ7.32 (m,3H), 6.96
(d, J = 8.6 Hz, 1H), 3.43 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 159.6, 154.0, 153.1, 132.4, 130.1,
129.6, 129.0, 128.1, 127.9, 126.6, 120.2, 118.9, 116.5, 116.1, 17.6; HRMS (ESI) m/z calcd for
C17H11BrNO2 [M + H]+ 339.9968, found 339.9969.
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2-(7-(Trifluoromethyl)-2-oxo-4-phenyl-2H-chromen-3-yl)acetonitrile (2l). Yellow oil (64.2 mg, 65%
yield); 1H NMR (400 MHz, CDCl3) δ 7.69–7.61 (m, 4H), 7.46 (dd, J = 8.3, 1.2 Hz, 1H), 7.35 (dd,
J = 7.6, 1.9 Hz, 2H), 7.25 (d, J = 8.3 Hz, 1H), 3.48 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 159.4,
153.5, 152.7, 134.0 (q, J = 33.8 Hz), 132.1, 130.3, 129.7, 128.9, 127.9, 124.5, 123.0 (q, J = 274.6
Hz), 121.2 (q, J = 3.5 Hz), 118.6, 115.9, 114.4 (q, J = 3.9 Hz), 17.7; HRMS (ESI) m/z calcd for
C18H11F3NO2 [M + H]+ 330.0736, found 330.0733.
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2-(6,8-Dimethyl-2-oxo-4-phenyl-2H-chromen-3-yl)acetonitrile (2m). Yellow solid (68.6 mg, 79%
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yield); mp 142–144 oC; H NMR (400 MHz, CDCl3) δ 7.64–7.56 (m, 3H), 7.32 (dd, J = 7.7, 1.5
Hz, 2H), 7.25 (s, 1H), 6.69 (s, 1H), 3.42 (s, 2H), 2.48 (s, 3H), 2.25 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 160.6, 154.9, 149.6, 135.0, 133.8, 133.4, 129.7, 129.4, 127.9, 126.1, 125.3, 119.3, 116.6,
115.7, 20.8, 17.5, 15.5; HRMS (ESI) m/z calcd for C19H16NO2 [M + H]+ 290.1176, found
290.1179.
2-(6-Chloro-2-oxo-4-phenyl-2H-chromen-3-yl)acetonitrile
(2n1)
and
2-(8-Chloro-2-oxo-4-phenyl-2H-chromen-3-yl)acetonitrile (2n2). Yellow oil (63.7 mg, 72% yield);
1H NMR (400 MHz, CDCl3) δ 7.66–7.60 (m, 5.20H), 7.53 (dd, J = 8.8, 2.5 Hz, 1.15H), 7.39–7.33
(m, 4.34H), 7.18–7.14 (m, 0.57H), 7.05 (d, J = 2.4 Hz, 0.92H), 7.01 (dd, J = 8.1, 1.5 Hz, 0.47H),
3.45 (s, 1H), 3.44 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 159.7, 159.2, 154.3, 153.5, 151.4, 148.8,
132.8, 132.6, 132.5, 132.2, 130.2, 130.2, 130.1, 129.7, 129.6, 127.9, 127.9, 127.2, 126.6, 124.7,
122.0, 121.3, 121.0, 118.5, 117.5, 117.1, 116.1, 17.6, 17.6; HRMS (ESI) m/z calcd for
C17H11ClNO2 [M + H]+ 296.0473, found 296.0470.
2-(2-Oxo-4-phenyl-2H-benzo[g]chromen-3-yl)acetonitrile (2o). Yellow solid (70.9 mg, 76%
o
yield); mp 150–151 C;1H NMR (400 MHz, CDCl3) δ 8.59 (s, 1H), 7.86 (s, 1H), 7.70–7.58 (m,
6H), 7.39–7.38 (m, 2H), 7.06 (d, J = 8.8 Hz, 1H), 3.50 (s, 2H); 13C NMR (100 MHz, CDCl3) δ
160.4, 155.5, 150.4, 135.0, 133.3, 129.8, 129.5, 129.3, 128.0, 127.8, 127.5, 124.5, 122.9, 122.8,
122.6, 116.5, 115.6, 115.0, 21.1; HRMS (ESI) m/z calcd for C21H14NO2 [M + H]+ 312.1019, found
312.1016.
2-(7-Methyl-2-oxo-4-p-tolyl-2H-chromen-3-yl)acetonitrile (2q). Yellow oil (47.7 mg, 55% yield);
1H NMR (400 MHz, CDCl3) δ 7.41 (d, J = 7.7 Hz, 2H), 7.21 (d, J = 7.8 Hz, 3H), 7.04–6.99 (m,
2H), 3.44 (s, 2H), 2.49 (s, 3H), 2.47 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 160.7, 154.9, 153.1,
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143.9, 139.9, 130.1, 130.0, 127.9, 127.7, 125.8, 117.6, 117.1, 116.7, 114.9, 21.7, 21.4, 17.5;
HRMS (ESI) m/z calcd for C19H16NO2 [M + H]+ 290.1176, found 290.1178.
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2-(4-(4-Methoxyphenyl)-7-methyl-2-oxo-2H-chromen-3-yl)acetonitrile (2r). Yellow oil (58.6 mg,
64% yield);1H NMR (400 MHz, CDCl3) δ 7.26 (d, J = 8.5 Hz, 2H), 7.20 (s, 1H), 7.11 (d, J = 8.6
Hz, 2H), 7.03 (s, 2H), 3.92 (s, 3H), 3.45 (s, 2H), 2.46 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
160.7, 160.6, 154.6, 153.1, 143.9, 129.5, 127.7, 125.8, 125.0, 117.7, 117.1, 116.8, 115.0, 114.8,
55.5, 21.7, 17.5; HRMS (ESI) m/z calcd for C19H16NO3 [M + H]+ 306.1125, found 306.1127.
2-(4-(4-tert-Butylphenyl)-7-methyl-2-oxo-2H-chromen-3-yl)acetonitrile (2s). Yellow solid (59.6
mg, 60% yield); mp 210–211 oC; 1H NMR (400 MHz, CDCl3) δ 7.62–7.60 (m, 2H), 7.28–7.24 (m,
3H), 7.03 (d, J = 0.8 Hz, 2H), 3.44 (s, 2H), 2.48 (s, 3H), 1.43 (s, 9H);13C NMR (100 MHz, CDCl3)
δ 160.7, 154.9, 153.1, 153.0, 143.9, 130.0, 127.8, 127.8, 126.3, 125.8, 117.6, 117.1, 116.9, 114.9,
35.0, 31.3, 21.7, 17.6; HRMS (ESI) m/z calcd for C22H22NO2 [M + H]+ 332.1645, found
332.1647.
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2-(4-(4-Fluorophenyl)-7-methyl-2-oxo-2H-chromen-3-yl)acetonitrile (2t). Yellow solid (59.8 mg,
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68% yield); mp 127–128 C; H NMR (400 MHz, CDCl3) δ 7.37–7.30 (m, 4H), 7.24 (s, 1H),
7.07–7.04 (m, 1H), 6.95 (d, J = 8.2 Hz, 1H), 3.44 (s, 2H), 2.48 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 163.3 (d, J = 249.2 Hz), 160.4, 153.7, 153.1, 144.2, 130.1 (d, J = 8.4 Hz), 129.8 (d, J =
16.0Hz), 128.9 (d, J = 3.6 Hz), 127.4, 126.1, 117.4, 117.2, 116.8 (d, J = 22.0 Hz), 115.9 (d, J =
115.0Hz), 21.7, 17.4; HRMS (ESI) m/z calcd for C18H13FNO2 [M + H]+ 294.0925, found
294.0924.
2-(4-(4-Chlorophenyl)-7-methyl-2-oxo-2H-chromen-3-yl)acetonitrile (2u). Yellow solid (60.3 mg,
65% yield); mp 145–146 oC; 1H NMR (400 MHz, CDCl3) δ 7.60 (d, J = 8.3 Hz, 2H), 7.30 (d, J =
8.4 Hz, 2H), 7.22 (s, 1H), 7.06–7.04 (m, 1H), 6.94 (d, J = 8.1 Hz, 1H), 3.42 (s, 2H), 2.47 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 160.3, 153.4, 153.1, 144.3, 136.1, 131.4, 129.8, 129.5, 127.3,
126.0, 117.2, 117.1, 116.4, 115.3, 21.7, 17.4; HRMS (ESI) m/z calcd for C18H13ClNO2 [M + H]+
310.0629, found 310.0628.
2-(4-(4-Bromophenyl)-7-methyl-2-oxo-2H-chromen-3-yl)acetonitrile (2v). Yellow solid (65.7 mg,
62% yield); mp 124–125 oC; 1H NMR (400 MHz, CDCl3) δ 7.77–7.75 (m, 2H), 7.24–7.22 (m, 3H),
7.06–7.04 (m, 1H), 6.94 (d, J = 8.2 Hz, 1H), 3.43 (s, 2H), 2.48 (s, 3H); 13C NMR (100 MHz,
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HRMS (ESI) m/z calcd for C18H13BrNO2 [M + H]+ 354.0124, found 354.0123.
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2-(4-(3-Chlorophenyl)-7-methyl-2-oxo-2H-chromen-3-yl)acetonitrile (2w). Yellow solid (58.4 mg,
63% yield); mp 119–120 oC;1H NMR (400 MHz, CDCl3) δ 7.58 (d, J = 3.9 Hz, 2H), 7.33 (s, 1H),
7.29–7.24 (m, 2H), 7.06 (d, J = 8.1 Hz, 1H), 6.95–6.92 (m, 1H), 3.52–3.36 (m, 2H), 2.48 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 160.3, 153.1, 153.0, 144.4, 135.6, 134.7, 130.9, 130.1, 128.0,
127.3, 126.3, 126.1, 117.2, 117.0, 116.3, 115.3, 21.7, 17.4; HRMS (ESI) m/z calcd for
C18H13ClNO2 [M + H]+ 310.0629, found 310.0626.
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2-(7-Methyl-2-oxo-4-m-tolyl-2H-chromen-3-yl)acetonitrile (2x). Yellow oil (43.4 mg, 50%
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yield); H NMR (400 MHz, CDCl3) δ 7.50–7.47 (m, 1H), 7.38 (d, J = 7.9 Hz, 1H), 7.22 (s, 1H),
7.12–7.10 (m, 2H), 7.04–6.98 (m, 2H), 3.42 (s, 2H), 2.47 (s, 6H); 13C NMR (100 MHz, CDCl3) δ
160.6, 154.9, 153.1, 143.9, 139.3, 133.0, 130.5, 129.3, 128.4, 127.7, 125.9, 125.0, 117.5, 117.0,
116.7, 114.8, 21.7, 21.5, 17.5; HRMS (ESI) m/z calcd for C19H16NO2 [M + H]+ 290.1176, found
290.1177.
2-(4-([1,1'-Biphenyl]-4-yl)-7-methyl-2-oxo-2H-chromen-3-yl)acetonitrile (2y). Yellow solid (67.4
mg, 64% yield); mp 110–111 oC; 1H NMR (400 MHz, CDCl3) δ 7.84 (d, J = 8.3 Hz, 2H), 7.71 (dd,
J = 5.2, 3.3 Hz, 2H), 7.54 (dd, J = 10.2, 4.8 Hz, 2H), 7.45–7.41 (m, 3H), 7.28 (d, J = 7.3 Hz, 1H),
7.07 (s, 2H), 3.50 (s, 2H), 2.50 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 160.6, 154.4, 153.2, 144.1,
142.7, 139.8, 131.8, 129.1, 128.5, 128.1, 128.0, 127.6, 127.2, 125.9, 117.4, 117.2, 116.7, 115.1,
21.7, 17.6; HRMS (ESI) m/z calcd for C24H18NO2 [M + H]+ 352.1332, found 352.1330.
2-(7-Methyl-4-(naphthalen-2-yl)-2-oxo-2H-chromen-3-yl)acetonitrile (2z). Yellow oil (61.4 mg,
63% yield);1H NMR (400 MHz, CDCl3) δ 8.09 (d, J = 8.5 Hz, 1H), 8.01–7.94 (m, 2H), 7.85 (d, J
= 0.7 Hz, 1H), 7.69–7.62 (m, 2H), 7.41 (dd, J = 8.4, 1.7 Hz, 1H), 7.28–7.27 (m, 1H), 7.04–6.99 (m,
2H), 3.51–3.42 (m, 2H), 2.49 (s, 3H);13C NMR (100 MHz, CDCl3) δ 160.6, 154.7, 153.1, 144.1,
133.4, 133.0, 130.4, 130.2, 129.4, 128.5, 128.4, 128.0, 127.7, 127.6, 127.6, 127.4, 125.9, 125.0,
117.5, 117.2, 116.7, 115.2, 21.7, 17.6; HRMS (ESI) m/z calcd for C22H16NO2 [M + H]+ 326.1176,
found 326.1176.
3-(2-Oxopropyl)-4-phenyl-2H-chromen-2-one (3a). Yellow solid (56.7 mg, 68% yield); mp 123–
o
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124 C; H NMR (400 MHz, CDCl3) δ 7.54–7.49 (m, 4H), 7.40 (dd, J = 8.3, 1.0 Hz, 1H), 7.28–
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7.26 (m, 2H), 7.19–7.15 (m, 1H), 7.04 (dd, J = 8.0, 1.5 Hz, 1H), 3.52 (s, 2H), 2.20 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 204.8, 161.6, 153.0, 152.8, 134.2, 131.3, 129.1, 128.9, 128.1, 127.4,
124.2, 121.0, 120.4, 116.8, 43.1, 30.2; HRMS (ESI) m/z calcd for C18H15O3 [M + H]+ 279.1016,
found 279.1011.
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7-Ethyl-3-(2-oxopropyl)-4-phenyl-2H-chromen-2-one (3c). Yellow oil (68.0 mg, 74% yield); H
NMR (400 MHz, CDCl3) δ 7.51 (dd, J = 5.1, 1.9 Hz, 3H), 7.27–7.23 (m, 3H), 7.00 (d, J = 1.6 Hz,
1H), 6.94 (d, J = 8.2 Hz, 1H), 3.49 (s, 2H), 2.74 (q, J = 7.6 Hz, 2H), 2.18 (s, 3H), 1.27 (t, J = 7.6
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 204.9, 161.9, 153.1, 148.7, 134.4, 129.0, 128.8, 128.1,
127.2, 124.2, 119.8, 118.2, 115.7, 43.0, 30.2, 28.8, 15.2; HRMS (ESI) m/z calcd for C20H19O3 [M
+ H]+ 307.1329, found 307.1329.
7-tert-Butyl-3-(2-oxopropyl)-4-phenyl-2H-chromen-2-one (3e). Yellow oil (78.2 mg, 78% yield);
1H NMR (400 MHz, CDCl3) δ 7.51 (dd, J = 5.0, 1.9 Hz, 3H), 7.41 (d, J = 1.9 Hz, 1H), 7.28–7.19
(m, 3H), 6.97 (d, J = 8.4 Hz, 1H), 3.50 (s, 2H), 2.18 (s, 3H), 1.35 (s, 9H); 13C NMR (100 MHz,
CDCl3) δ 204.9, 162.0, 155.7, 152.9, 152.9, 134.4, 129.0, 128.8, 128.1, 127.0, 121.7, 120.0, 118.0,
113.5, 43.0, 35.1, 31.1, 30.2; HRMS (ESI) m/z calcd for C22H23O3 [M + H]+ 335.1642, found
335.1640.
7-Bromo-3-(2-oxopropyl)-4-phenyl-2H-chromen-2-one (3k). Yellow solid (74.8 mg, 70% yield);
mp 101–102 oC; 1H NMR (400 MHz, CDCl3) δ 7.55–7.50 (m, 4H), 7.29–7.23 (m, 3H), 6.89 (d, J
= 8.5 Hz, 1H), 3.49 (s, 2H), 2.18 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 204.5, 160.9, 153.0,
152.4, 133.7, 129.3, 129.1, 128.5, 128.0, 127.6, 125.1, 121.3, 119.9, 119.5, 43.1, 30.3; HRMS
(ESI) m/z calcd for C18H14BrO3 [M + H]+ 357.0121, found 357.0120.
Methyl 2-(2-oxo-4-phenyl-2H-chromen-3-yl)acetate (4a).23 Yellow solid (122.0 mg, 83% yield);
mp 115–116 oC; 1H NMR (400 MHz, CDCl3) δ 7.56–7.49 (m, 4H), 7.38 (dd, J = 8.3, 0.8 Hz, 1H),
7.30–7.28 (m, 2H), 7.19–7.14 (m, 1H), 7.05 (dd, J = 8.0, 1.5 Hz, 1H), 3.67 (s, 3H); 3.41 (s, 2H);
13C NMR (100 MHz, CDCl3) δ 170.8, 161.5, 153.0, 152.9, 134.0, 131.5, 129.2, 129.0, 128.2,
127.6, 124.3, 120.4, 120.2, 116.8, 52.2, 34.2.
2-(2-Oxo-4-phenyl-2H-chromen-3-yl)acetamide (5a). Yellow solid (128.4 mg, 92% yield); mp 89–
90 oC; 1H NMR (400 MHz, DMSOꢀd6) δ 7.61–7.54 (m, 4H), 7.47 (d, J = 8.3 Hz, 1H), 7.39 (s, 1H),
7.34 (d, J = 7.5 Hz, 2H), 7.27–7.23 (m, 1H), 6.95 (d, J = 8.1 Hz, 2H), 3.12 (s, 2H); 13C NMR (100
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MHz, DMSOꢀd6) δ 171.2, 161.2, 152.7, 152.1, 134.4, 131.8, 129.4, 129.3, 128.6, 127.4, 124.9,
121.8, 120.6, 116.8, 35.6; HRMS (ESI) m/z calcd for C17H14NO3 [M + H]+ 280.0968, found
280.0970.
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■ ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at DOI:
Copies of 1H NMR and 13C NMR spectra for all products, and the crystal structures of 2h and 2u.
■ AUTHOR INFORMATION
Corresponding Author
*Eꢀmail: sunpeipei@njnu.edu.cn
Notes
The authors declare no competing financial interest.
■ ACKNOWLEDGMENTS
This work was supported by the National Natural Science Foundation of China (Project 21272117,
21502097, 21672104), the Key International (Regional) Joint Research Program of NSFC (Grant
No. 21420102002), the Natural Science Foundation of the Education Department of Jiangsu
province (15KJB150015), and the Priority Academic Program Development of Jiangsu Higher
Education Institutions. The authors also thank Mr. Hailong Liu for the determination of HRMS.
■ REFERENCES
(1) (a) Rappoport, Z. Chemistry of the Cyano Group; John Wiley & Sons: London, 1970. (b)
Fleming, F. F. Nat. Prod. Rep. 1999, 16, 597. (c) Fleming, F. F.; Yao, L.; Ravikumar, P. C.; Funk,
L.; Shook, B. C. J. Med. Chem. 2010, 53, 7902.
(2) (a) Larock, R. C. Comprehensive Organic Transformations: A Guide to Functional Group
Preparations; VCH: New York, 1989. (b) Anbarasan, P.; Schareina, T.; Beller, M. Chem. Soc. Rev.
2011, 40, 5049. (c) Wang, M.ꢀX. Acc. Chem. Res. 2015, 48, 602.
(3) (a) Wang, R.; Falck, J. R. RSC Adv. 2014, 4, 1062. (b) Wen, Q.; Lu, P.; Wang, Y. RSC Adv.
2014, 4, 47806. (c) Kou, X.; Fan, J.; Tong, X.; Shen, Z. Chin. J. Org. Chem. 2013, 33, 1407.
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Page 17 of 18
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
(4) (a) Chatani, N.; Hanafusa, T. J. Org. Chem. 1986, 51, 4714. (b) Sammis, G. M.; Jacobsen,
E. N. J. Am. Chem. Soc. 2003, 125, 4442. (c) Mita, T.; Sasaki, K.; Kanai, M.; Shibasaki, M. J. Am.
Chem. Soc. 2005, 127, 514. (d) Yamaguchi, K.; Xu, N.; Jin, X.; Suzuki K.; Mizuno, N. Chem.
Commun. 2015, 51, 10034.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(5) (a) Anbarasan, P.; Neumann, H.; Beller, M. Angew. Chem., Int. Ed. 2011, 50, 519. (b) Pawar,
A. B.; Chang, S. Org. Lett. 2015, 17, 660.
(6) (a) Gong, T.ꢀJ.; Xiao, B.; Cheng, W.ꢀM.; Su, W.; Xu, J.; Liu, Z.ꢀJ.; Liu, L.; Fu, Y. J. Am.
Chem. Soc. 2013, 135, 10630. (b) Li, J.; Ackermann, L. Angew. Chem., Int. Ed. 2015, 54, 3635. (c)
Liu, W.; Ackermann, L. Chem. Commun. 2014, 50, 1878. (d) Dong, J.; Wu, Z.; Liu, Z.; Liu, P.;
Sun, P. J. Org. Chem. 2015, 80, 12588.
(7) (a) Kou, X.; Zhao, M.; Qiao, X.; Zhu, Y.; Tong, X.; Shen, Z. Chem.–Eur. J. 2013, 19, 16880.
(b) Zhu, Y.; Zhao, M.; Lu, W.; Li, L.; Shen, Z. Org. Lett. 2015, 17, 2602. (c) Zhu, Y.; Li, L.; Shen,
Z. Chem.–Eur. J. 2015, 21, 13246. (d) Pan, C.; Jin, H.; Xu, P.; Liu, X.; Cheng, Y.; Zhu, C. J. Org.
Chem. 2013, 78, 9494. (e) Zhao, M.; Zhang, W.; Shen, Z. J. Org. Chem. 2015, 80, 8868.
(8) Lypez, R.; Palomo, C. Angew. Chem., Int. Ed. 2015, 54, 13170.
(9) (a) Li, Y.; Liu, B.; Li, H.ꢀB.; Wang, Q.; Li, J.ꢀH. Chem. Commun. 2015, 51, 1024. (b)
Bunescu, A.; Wang, Q.; Zhu, J. Angew. Chem., Int. Ed. 2015, 54, 3132. (c) ChatalovaꢀSazepin, C.;
Wang, Q.; Sammis, G. M.; Zhu, J. Angew. Chem., Int. Ed. 2015, 54, 5443. (d) Li, Z.; Xiao, Y.; Liu,
Z.ꢀQ. Chem. Commun. 2015, 51, 9969. (e) Pan, C.; Zhang, H.; Zhu, C. Org. Biomol. Chem. 2015,
13, 361. (f) Chu, X.ꢀQ.; Xing, Z.ꢀH.; Meng, H.; Xu, X.ꢀP.; Ji, S.ꢀJ. Org. Chem. Front. 2016, 3,
165.
(10) (a) Santana, L.; Uriarte, E.; Roleira, F.; Milhazes, N.; Borges, F. Curr. Med. Chem. 2004,
11, 3239. (b) Dandriyal, J.; Singla, R.; Kumar, M.; Jaitak, V. Eur. J. Med. Chem. 2016, 119, 141. (c)
Xu, Q.; Ouyang, J.; Yang, Y.; Ito, T.; Kido, J. Appl. Phys. Lett. 2003, 83, 4695.
(11) Mantovani, A. C.; Goulart, T. A. C.; Back, D. F.; Menezes, P. H.; Zeni, G. J. Org.
Chem. 2014, 79, 10526.
(12) Li, Y.; Lu, Y.; Qiu, G.; Ding, Q. Org. Lett. 2014, 16, 4240.
(13) Mi, X.; Wang, C.; Huang, M.; Zhang, J.; Wu, Y.; Wu, Y. Org. Lett. 2014, 16, 3356.
(14) Wei, W.; Wen, J.; Yang, D.; Guo, M.; Wang, Y.; You, J.; Wang, H. Chem. Commun. 2015,
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Page 18 of 18
1
2
3
51, 768.
4
5
6
7
8
9
(15) Yang, W.; Yang, S.; Li, P.; Wang, L. Chem. Commun. 2015, 51, 7520.
(16) (a) Yan, K.; Yang, D.; Wei, W.; Wang, F.; Shuai, Y.; Li, Q.; Wang, H. J. Org. Chem. 2015,
80, 1550. (b) Liu, T.; Ding, Q.; Zong, Q. Qiu, G. Org. Chem. Front. 2015, 2, 670.
(17) Fu, W.; Zhu, M.; Zou, G.; Xu, C.; Wang, Z.; Ji, B. J. Org. Chem. 2015, 80, 4766.
(18) Ni, S.; Cao, J.; Mei, H.; Han, J.; Li, S.; Pan, Y. Green Chem. 2016, 18, 3935.
(19) Liu, T.; Ding, Q.; Qiu, G.; Wu, J. Tetrahedron 2016, 72, 279.
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11
12
13
14
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25
26
27
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41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(20) (a) Ji, J.; Liu, P.; Sun, P. Chem. Commun. 2015, 51, 7546. (b) Du, B.; Jin, B.; Sun, P. Org.
Lett. 2014, 16, 3032. (c) Xu, Y.; Cong, T.; Liu, P.; Sun, P. Org. Biomol. Chem. 2015, 13, 9742.
(21) CCDC 1501379 (2h) and CCDC 1495624 (2u) contain supplementary crystallographic
data for this paper.
(22) Song, C. E.; Jung, D.; Choung, S. Y.; Roh, E. J.; Lee, S. Angew. Chem., Int. Ed. 2004, 43,
6183.
(23) Gabriele, B.; Mancuso, R.; Salerno, G.; Plastina, P. J. Org. Chem. 2008, 73, 756.
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