AgI-Promoted Difluoromethylation of Isocyanides To Give Difluoromethylated Phenanthridines

Article abstract of DOI:10.1002/ejoc.201700470

An Ag^I-mediated ethoxycarbonyldifluoromethylation of isocyanides has been developed. This radical cascade reaction involves the addition of difluoromethylene radical to the isocyanide functionality, and subsequent homolytic aromatic substitution to give difluoromethylated phenanthridines with a good functional-group tolerance.

Full text of DOI:10.1002/ejoc.201700470

DOI: 10.1002/ejoc.201700470
Full Paper
Radical Difluoromethylation
AgI-Promoted Difluoromethylation of Isocyanides To Give
Difluoromethylated Phenanthridines
Wen Wan*[a] Xiaochen Xu,[a] Yunrong Chen,[a] Haizhen Jiang,[a] Yong Wang,[a]
Hongmei Deng,[b] and Jian Hao*[a,c]
Abstract: An AgI-mediated ethoxycarbonyldifluoromethylation isocyanide functionality, and subsequent homolytic aromatic
of isocyanides has been developed. This radical cascade reac- substitution to give difluoromethylated phenanthridines with a
tion involves the addition of difluoromethylene radical to the good functional-group tolerance.
Introduction
With respect to the CF2CO2Et moiety, to date, only Yu's group
has reported a method for the ethoxycarbonyldifluoromethyl-
ation of isocyanides; they used BrCF2CO2Et as a fluoroalkylating
reagent and fac-Ir(ppy)3 (ppy = 2-phenylpyridinato) as a photo-
redox catalyst.[7] Despite these important advances, current
strategies for the ethoxycarbonyldifluoromethylation of phen-
anthridines still suffer from the disadvantages that they require
expensive photoredox catalysts, and have limited substrate
scope. This greatly limits their use on a large scale in synthesis
and in the industry. Therefore, it is highly desirable to develop
a simple, convenient, efficient and alternative strategy to ad-
dress the synthesis of more diverse CF2CO2Et-containing phen-
anthridines through the difluoromethylation of biaryl isocyan-
ides.
Our group has always been interested in difluoromethyl-
ation. We reported an AgI-mediated ethoxycarbonyldifluoro-
methylation of terminal unactivated or activated alkenes and
aromatic rings, and constructed a wide range of complex
oxindoles with a terminal CF2CO2Et group through a radical
process.[8] Inspired by recent reports on cascade radical addi-
tion/cyclization reactions to form functionalized phenanthrid-
ines, we decided to investigate the modular synthesis of phen-
anthridines bearing a terminal CF2CO2Et group.
It is well known that the incorporation of a fluorine-containing
functional group into organic molecules such as pharmaceuti-
cals and agrochemicals has been considered to be a good strat-
egy in drug design. Such modifications can enhance the bind-
ing interactions and metabolic stabilities of the molecules, and
change their physical properties and reactivities.[1] The gem-
difluoromethylene unit (CF2) is of particular interest due to its
unique behaviour as a bioisostere, mimicking the steric and
electronic features of an oxygen atom or a carbonyl group. This
can often lead to increased dipole moments, enhanced acidity
of neighbouring groups and conformational changes.[2] Re-
cently, significant progress has been made in the difluorometh-
ylation of aromatic compounds.[3] Among the functionalized di-
fluoro moieties that have been reported, the CF2CO2Et moiety
is extremely appealing. It can be transformed into a variety of
other difluoromethylene-containing functional groups, which
overcomes the drawbacks of the recently reported perfluoro-
alkyl groups.
Phenanthridines are biologically important compounds that
occur in nature and are used as drugs or as drug candidates in
medicinal chemistry.[4] These heterocycles show antibacterial,
antitumoral, cytotoxic and antileukemic activities.[5] Fluorine-
containing phenanthridines have received great attention in re-
cent years. However, to the best of knowledge, only a handful
of examples have been developed to date in which a difluoro-
methylene moiety is incorporated into the phenanthridine.[6]
Results and Discussion
The reaction was optimized by using biaryl isocyanide 1a in
combination with Me3SiCF2CO2Et (2) as a difluoromethyl radical
precursor in the presence of an AgI salt, PhI(OAc)2 as an oxidant
and NaOAc as an initiator, at ambient temperature (Table 1). To
our delight, the target phenanthridine 3a was obtained in 6 %
yield, as determined by 19F NMR spectroscopy (Table 1, entry 1).
A variety of silver(I) salts, including Ag2CO3, AgBF4, AgOTf, AgF,
AgOAc and AgNO3, were evaluated, and we found that Ag2CO3
gave a somewhat better yield (Table 1, entries 1–6). A solvent
screen revealed that the use of 1,4-dioxane improved the yield
to 15 % (Table 1, entries 7–11). Different bases were tested, in-
cluding K2CO3, KOH, Et3N, tBuONa and K3PO4, and we found
that the yield of the reaction improved marginally to 47 %
[a] Department of Chemistry, Innovative Drug Research Center,
Shanghai University,
Shangda Road 99, Shanghai, China
E-mail: wanwen@shu.edu.cn; jhao@shu.edu.cn
http://www.chem.shu.edu.cn
[b] Laboratory of Microstructures, Shanghai University,
China
[c] Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences,
Ling Ling Road 345, Shanghai, China
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.201700470.
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when K2CO3 (0.5 equiv.) was used (Table 1, entries 12–17). A to be well tolerated under the standard conditions, and the
higher loading of K2CO3 (3.0 equiv.) improved the efficiency of difluoromethylated phenanthridines 3d, 3e and 3g were
the reaction, giving a yield of 72 % (Table 1, entry 13). Extension formed. These could then be subjected to further modification
of the reaction time to 48 h resulted in a lower yield and the at the substituted positions. Notably, aromatic heterocycles
formation of a complex mixture (Table 1, entry ). Increasing could be incorporated into the phenanthridine scaffold in rea-
the temperature to 50 °C resulted in a lower conversion to the sonable yields, which makes this approach more useful for the
expected product, and a 52 % yield (Table 1, entry 19). Replace- preparation of pharmaceuticals and gem-difluoromethylene-
ment of the nucleophilic reagent NaOAc with LiOAc or KOAc linked identical or nonidentical twin drugs twin drugs. For in-
did not improve the efficiency of the reaction (Table 1, stance, replacement of a benzene ring from the biaryl isocyan-
entries 20 and 21). Decreasing the amount of Me3SiCF2CO2Et ides with pyridine or thiophene moiety was compatible with
resulted in lower yields of the target compound 3a (Table 1, these cyclization reaction conditions. A substrate bearing an
entries 22 and 23).
electron-deficient pyridine moiety instead of a phenyl ring was
cyclized to give a benzo[c][2,7]naphthyridine scaffold 3k in a
reasonable yield (35 %). A substrate containing an electron-rich
thienyl moiety instead of a phenyl ring, 2-(2-thienyl)phenyl iso-
cyanide (1k), was also found to be a suitable substrate for this
annulation reaction, and thieno[3,2-c]quinoline system 3l was
formed in 17 % yield. Interestingly, when 1-(2-isocyanophenyl)-
1H-pyrrole (1m) was used in this annulation, a mixture of
mono- and bis-ethoxycarbonyldifluoromethylated pyrrolo[1,2-
a]quinoxalines was obtained in 26 % (3m) and 34 % (3m′)
yields.
Table 1. Survey of reaction conditions.[a]
Entry
AgI salt
(2.5 equiv.) (3.0 equiv.)
Nucleophile Base
Solvent
Temp Yield
[°C]
(equiv.)
[%][b]
1
2
3
4
5
6
7
8
Ag2CO3
AgBF4
AgOTf
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
LiOAc
–
–
–
–
–
–
–
–
–
–
–
NMP
NMP
NMP
NMP
NMP
NMP
DMSO
DMF
CH3CN
THF
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
6
1
4
1
4
3
3
3
Table 2. Scope of the difluoromethylenation reaction of biaryl isocyanides
with 2.[a,b]
AgF
AgOAc
AgNO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
9
0
2
10
11
12
13
14
15
16
17
18
19
20
21
22
23
1,4-dioxane r.t.
15
47
72
26
36
45
12
65
52
61
58
43
39
K2CO3 (0.5) 1,4-dioxane r.t.
K2CO3 (3)
Et3N (3)
K3PO4 (3)
NaOH (3)
tBuONa (3) 1,4-dioxane r.t.
K2CO3 (3)
K2CO3 (3)
K2CO3 (3)
K2CO3 (3)
K2CO3 (3)
K2CO3 (3)
1,4-dioxane r.t.
1,4-dioxane r.t.
1,4-dioxane r.t.
1,4-dioxane r.t.
1,4-dioxane r.t.[c]
1,4-dioxane 50
1,4-dioxane r.t.
1,4-dioxane r.t.
1,4-dioxane r.t.[d]
1,4-dioxane r.t.[e]
KOAc
NaOAc
NaOAc
[a] Reaction conditions: 2-isocyanobiphenyl (1a; 0.2 mmol), TMSCF2CO2Et (2;
TMS trimethylsilyl;
mmol), AgI salt (2.5 equiv.), PhI(OAc)2 oxidant
=
1
(2.0 equiv.), initiator (3.0 equiv.) and base in solvent (3.0 mL) for 24 h under
a nitrogen atmosphere. [b] Yields determined by 19F NMR spectroscopic anal-
ysis with PhCF3 as the internal standard. [c] Reaction time: 48 h. [d] Ratio of
1a/2 was 1:2. [e] Ratio of 1a/2 was 1:1.
Encouraged by these results, a variety of biphenyl isocyan-
ides 1a–1m were used to react with Me3SiCF2CO2Et (2) under
the optimized reaction conditions (Table 1, entry 13), in order
to study the scope and limitations of this transformation. As
shown in Table 2, the corresponding 6-difluoromethylated
phenanthridine derivatives were formed in moderate to good
yields. The substituents on both benzene rings did not affect
this transformation significantly. Electron-withdrawing substitu-
ents, such as chloro or acetyl groups, on the aryl rings proved
[a] Standard reaction conditions: 2-isocyanobiphenyl (1a; 0.2 mmol),
TMSCF2CO2Et (2; 1 mmol), Ag2CO3(2.5 equiv.), PhI(OAc)2 (2.0 equiv.), NaOAc
(3.0 equiv.) K2CO3 (3.0 equiv.) in 1,4-dioxane (3.0 mL) for 24 h under a nitro-
gen atmosphere. [b] Isolated yield.
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To test whether an in-situ-generated (ethoxycarbonyl)di- to generate isocyanide derivative F containing a difluorometh-
fluoromethyl radical species (·CF2CO2Et) was involved in the re- ylated pyrrole moiety. Subsequent addition of a second
action, we carried out an inhibition experiment on the reaction ·CF2CO2Et radical to isocyanide F produces the imidoyl radical
of 1a through the addition of the known radical scavenger G. This then cyclizes onto the pyrrole to give dihydropyrrole
TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy; 2.0 equiv.) under radical K. Oxidation of K and further rearomatization gives
the standard reaction conditions (see Supporting Information). pyrrolo[1,2-a]quinoxaline 3m′, which bears two CF2CO2Et
Complete suppression of the desired reaction was observed, groups on its heterocyclic scaffold.
and the formation of TEMPO-CF2CO2Et was detected by 19F
·
NMR spectroscopy. This suggests that a CF2CO2Et radical spe-
cies is involved in this reaction and initiates the cascade se-
quence through addition to the isocyanide, which is consistent
with literature precedent.[8c,9]
An annulation was proposed as the mechanism of these re-
·
actions (Scheme 1). Firstly, CF2CO2Et radical intermediate A is
generated and further stabilized by the combination of AgI and
PhI(OAc)2. Addition of the ·CF2CO2Et radical intermediate to the
isocyanide generates the imidoyl radical B, which cyclizes onto
the arene to give cyclohexadienyl radical C. Oxidation of C pro-
duces the corresponding carbocation D. Finally, intermediate D
is deprotonated, which leads to rearomatization to give the de-
sired gem-difluoromethylenated phenanthridine E.
Scheme 2. Proposed reaction mechanism for the formation of 3m′.
Conclusions
An efficient and convenient method for the synthesis of ethoxy-
carbonyldifluoromethylated phenanthridines has been devel-
oped by means of an AgI-mediated cascade gem-difluorometh-
ylenation/cyclization of isocyanides with TMSCF2CO2Et under
Scheme 1. Proposed reaction mechanism for the formation of 3a–3m.
mild reaction conditions. This provides an alternative strategy
As noted above, aromatic heterocycles, such as pyridine,
for the synthesis of structurally diverse CF2CO2Et-containing
thiophene and pyrrole, were successfully incorporated into the
gem-difluoromethylenated phenanthridines. These compounds
phenanthridine scaffold. However, an exception was found
when bis-ethoxycarbonyldifluoromethylated phenanthridine
3m′ was obtained from an N-pyrrole-substituted isocyanide de-
rivative. To study the formation of this bis-ethoxycarbonyldi-
offer a range of possibilities for synthetic post-functionalization
for the preparation of pharmaceutically and biologically active
phenanthridine derivatives, as well as functional materials.
fluoromethylated phenanthridine, we carried out the reaction
of monoethoxycarbonyl difluoromethylated phenanthridine 3m
with an excess of TMSCF2CO2Et under the standard reaction
conditions. Unfortunately, a conversion of the substrate 3m into General Remarks: 1H, 13C and 19F NMR spectra were recorded in
Experimental Section
l
CDCl3 with a Bruker AV-500 spectrometer. Chemical shifts for H
NMR spectra are reported in ppm downfield from tetramethylsilane,
and residual CHCl3 was used as an internal reference (δ = 7.26 ppm
for 1H). Chemical shifts for 13C NMR spectra are reported in ppm,
and internal CDCl3 (δ = 77.16 ppm for 13C) was used as an internal
reference. Chemical shifts for 19F NMR spectra are reported in ppm
downfield from internal fluorotrichloromethane (CFCl3). Coupling
constants (J) are given in Hertz (Hz). The terms m, s, d, t and q refer
to multiplet, singlet, doublet, triplet and quartet, respectively; br.
refers to a broad signal. Infrared spectra (IR) were recorded with an
3m′ of less than 10 % was obtained, even when the reaction
time was extended to 72 h. This indicates that 3m′ was not
formed by direct difluoromethylation of the pyrrole ring from
pyrrolo[1,2-a]quinoxaline derivative 3m. These results suggest
that a C–H difluoromethylation of the pyrrole ring takes place
before difluoromethylation of the isocyanide functionality.[10]
Thus, a more reasonable mechanism for the formation of 3m′
is proposed as shown in Scheme 2. Firstly, the in-situ-generated
·CF2CO2Et radical intermediate undergoes direct C–H difluoro-
methylation at the α position of the electron-rich pyrrole ring Avatar 370 FTIR spectrometer, absorbance frequencies are given at
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maximum intensity in cm–1. Melting points were obtained with an
X-4 digital melting-point apparatus. High-resolution mass spectra
(HRMS) and mass spectra (MS) were recorded using the electron
impact (EI) or electrospray ionization (ESI) techniques.
chlorophenyl)boronic acid was used instead of phenylboronic acid.
Compound 1d was obtained (88 % over two steps) as an off-white
solid. 1H NMR (500 MHz, CDCl3): δ = 7.52–7.42 (m, 6 H), 7.39 (dd,
J = 7.9, 6.5 Hz, 2 H) ppm.
1-(2′-Isocyano-[1,1′-biphenyl]-4-yl)ethan-1-one (1e): This com-
pound was prepared by the same procedure described for 1a, ex-
cept that (4-acetylphenyl)boronic acid was used instead of phenyl-
boronic acid. Compound 1e was obtained (82 % over two steps) as
an off-white solid. 1H NMR (500 MHz, CDCl3): δ = 8.10–8.05 (m, 2
H), 7.65–7.59 (m, 2 H), 7.55–7.47 (m, 2 H), 7.47–7.40 (m, 2 H), 2.66
(s, 3 H) ppm.
General Procedure for Synthesis of Substrates (Derivatives of
Isocyanides):[11] 2-Bromoaniline (20 mmol), phenylboronic acid
(24 mmol), K2CO3 (2
M aq.; 45 mL) and DME (40 mL) were added to
an oven-dried three-necked flask under a gentle stream of nitrogen.
The mixture was stirred for 30 min at room temperature under a
nitrogen atmosphere. PdCl2(PPh3)2 (280 mg, 0.40 mmol) was then
added at room temperature, and the mixture was stirred overnight
at 80 °C under nitrogen. The reaction mixture was then cooled to
room temperature and diluted with EtOAc. The organic layer was
washed with water and dried with MgSO4, and the volatiles were
removed in vacuo. The residue was subjected to column chroma-
tography on silica gel (petroleum ether/EtOAc, 30:1) to give [1,1′-
biphenyl]-2-amine (89 %).
2-Isocyano-5-methyl-1,1′-biphenyl (1f): This compound was pre-
pared by the same procedure described for 1a, except that 2-
bromo-4-methylaniline was used instead of 2-bromoaniline. Com-
pound 1f was obtained (88 % over two steps) as a pale yellow solid.
1H NMR (500 MHz, CDCl3): δ = 7.52–7.48 (m, 2 H), 7.48–7.45 (m, 2
H), 7.45–7.39 (m, 1 H), 7.37 (d, J = 8.1 Hz, 1 H), 7.23 (d, J = 2.0 Hz,
1 H), 7.17 (dd, J = 8.2, 1.9 Hz, 1 H), 2.41 (s, 3 H) ppm.
[1,1′-Biphenyl]-2-amine (18 mmol) and THF (30 mL) were added to
an oven-dried three-necked flask equipped with a dropping funnel
under a nitrogen atmosphere, and the solution was cooled to 0 °C.
Acetic formic anhydride [prepared from the reaction of acetic anhy-
dride (3.8 mL) with formic acid (1.7 mL) at 55 °C for 2 h] was trans-
ferred to the dropping funnel and added to the solution of [1,1′-
biphenyl]-2-amine dropwise at 0 °C. After the addition was com-
plete, the mixture was warmed to room temperature and stirred for
2 h. After this time, the reaction was quenched with sat. aqueous
NaHCO3, and the mixture was extracted with EtOAc (3 ×). The or-
ganic extract was dried with Na2SO4 and concentrated under re-
duced pressure to give the formamide as a pale yellow oil. This
material was used in the subsequent dehydration without further
purification.
5-Chloro-2-isocyano-1,1′-biphenyl (1g): This compound was pre-
pared by the same procedure described for 1a, except that 2-
bromo-4-chloroaniline was used instead of 2-bromoaniline. Com-
pound 1g was obtained (87 % over two steps) as an off-white solid.
1H NMR (500 MHz, CDCl3): δ = 7.53–7.45 (m, 5 H), 7.43 (dd, J = 5.4,
3.1 Hz, 2 H), 7.35 (dd, J = 8.5, 2.3 Hz, 1 H) ppm.
2-Isocyano-4-methoxy-1,1′-biphenyl (1h): This compound was
prepared by the same procedure described for 1a, except that 2-
bromo-5-methoxyaniline was used instead of 2-bromoaniline. Com-
1
pound 1h was obtained (86 % over two steps) as a green solid. H
NMR (500 MHz, CDCl3): δ = 7.51–7.43 (m, 4 H), 7.42–7.37 (m, 1 H),
7.34 (dd, J = 8.4, 0.6 Hz, 1 H), 7.07–6.96 (m, 2 H), 3.86 (s, 3 H) ppm.
2-Isocyano-5-trifluoromethyl-1,1′-biphenyl (1i): This compound
was prepared by the same procedure described for 1a, except that
2-bromo-4-trifluoromethyl-phenylamine was used instead of 2-
bromoaniline. Compound 1i was obtained (56 % over two steps) as
THF (30 mL), NEt3 (150 mmol) and all of the formamide obtained
above were added to an oven-dried three-necked flask equipped
with a dropping funnel under a nitrogen atmosphere. The resulting
solution was cooled to 0 °C. POCl3 (36 mmol) was added dropwise,
and the mixture was stirred for 2 h at 0 °C after the addition was
complete. After this time, the reaction was quenched with sat.
aqueous Na2CO3, and the mixture was stirred for 1 h. The mixture
was extracted with CH2Cl2 (3 ×). The organic phase was dried with
MgSO4, and the solvent was evaporated under reduced pressure.
The residue was purified by column chromatography (petroleum
ether/EtOAc, 40:1) to give 1a (78 %) as a green oil.
1
a dark blue solid. H NMR (500 MHz, CDCl3): δ = 7.71 (d, J = 2.0 Hz,
1 H), 7.67–7.60 (m, 2 H), 7.52 (d, J = 4.4 Hz, 4 H), 7.50–7.44 (m, 1 H)
ppm.
2-Isocyano-4′,5-dimethyl-1,1′-biphenyl (1j): This compound was
prepared by the same procedure described for 1a, except that 2-
bromo-4-methylaniline was used instead of 2-bromoaniline, p-tolyl-
boronic acid was used instead of phenylboronic acid. Compound
1j was obtained (82 % over two steps) as a pale green solid. 1H
NMR (500 MHz, CDCl3): δ = 7.42–7.38 (m, 2 H), 7.36 (d, J = 8.1 Hz,
1 H), 7.30–7.26 (m, 2 H), 7.21 (d, J = 1.9 Hz, 1 H), 7.14 (ddd, J = 8.0,
2.0, 0.8 Hz, 1 H), 2.41 (s, 3 H), 2.40 (s, 3 H) ppm.
2-Isocyano-1,1′-biphenyl (1a): Green oil. 1H NMR (500 MHz,
CDCl3): δ = 7.55–7.51 (m, 2 H), 7.51–7.47 (m, 3 H), 7.47–7.41 (m, 3
H), 7.38 (ddd, J = 7.9, 6.9, 2.0 Hz, 1 H) ppm.
2-Isocyano-4′-methyl-1,1′-biphenyl (1b): This compound was pre-
pared by the same procedure described for 1a, except that p-tolyl-
boronic acid was used instead of phenylboronic acid. Compound
1b was obtained (84 % over two steps) as a green oil. 1H NMR
(500 MHz, CDCl3): δ = 7.51 (dd, J = 7.9, 1.3 Hz, 1 H), 7.49–7.42 (m,
4 H), 7.38 (ddd, J = 7.9, 6.9, 2.1 Hz, 1 H), 7.32 (d, J = 7.9 Hz, 2 H),
2.45 (s, 3 H) ppm.
4-(2-Isocyanophenyl)pyridine (1k): This compound was prepared
by the same procedure described for 1a, except that pyridin-4-yl-
boronic acid was used instead of phenylboronic acid. Compound
1k was obtained (70 % over two steps) as a brown solid. M.p. 61–
63 °C. H NMR (500 MHz, CDCl3): δ = 8.79–8.69 (m, 2 H), 7.58–7.39
(m, 6 H) ppm.
1
2-(2-Isocyano-5-methylphenyl)thiophene (1l): This compound
was prepared by the same procedure described for 1a, except that
2-Bromo-4-methyl-phenylamine and thiophen-2-ylboronic acid was
used instead of 2-Bromo-phenylamine and phenylboronic acid.
Compound 1l was obtained (50 % over two steps) as a dark yellow
2-Isocyano-4′-methoxy-1,1′-biphenyl (1c): This compound was
prepared by the same procedure described for 1a, except that (4-
methoxyphenyl)boronic acid was used instead of phenylboronic
acid. Compound 1c was obtained (85 % over two steps) as a pale
green solid. 1H NMR (500 MHz, CDCl3): δ = 7.48–7.41 (m, 3 H), 7.41–
7.34 (m, 2 H), 7.23 (dd, J = 7.4, 1.7 Hz, 1 H), 7.09–6.99 (m, 2 H), 3.84
(s, 3 H) ppm.
1
solid. H NMR (500 MHz, CDCl3): δ = 7.53 (dd, J = 3.6, 1.2 Hz, 1 H),
7.42 (dd, J = 5.2, 1.2 Hz, 1 H), 7.36 (d, J = 8.2 Hz, 2 H), 7.15 (dd, J =
5.2, 3.6 Hz, 1 H), 7.12 (dd, J = 8.0, 1.9 Hz, 1 H), 2.40 (s, 3 H) ppm.
4′-Chloro-2-isocyano-1,1′-biphenyl (1d): This compound was pre- 1-(2-Isocyano-phenyl)-1H-pyrrole (1m): 2-Iodoaniline (20 mmol),
pared by the same procedure described for 1a, except that (4- pyrrole acid (24 mmol), CuI (2 mmol), DMEDA (N,N′-dimethylethyl-
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enediamine; 4 mmol), K3PO4 (44 mmol) and toluene (50 mL) were gave compound 3d (54 %) as a pale yellow solid. 1H NMR (500 MHz,
added to an oven-dried three-necked flask under a gentle stream
of nitrogen, and the mixture was stirred for 2 h at 110 °C. The
reaction mixture was then cooled to room temperature and diluted
with EtOAc. The organic layer was washed with water and dried
CDCl3): δ = 8.56 (d, J = 8.9 Hz, 1 H), 8.58 (d, J = 2.0 Hz, 1 H), 8.49–
8.46 (m, 1 H), 8.08 (dd, J = 6.1, 3.4 Hz, 1 H), 7.82 (dd, J = 8.9, 2.1 Hz,
1 H), 7.75 (dd, J = 6.2, 3.3 Hz, 2 H), 4.60 (q, J = 7.1 Hz, 2 H), 1.51 (t,
J = 7.1 Hz, 3 H) ppm. 19F NMR (471 MHz, CDCl3): δ = –98.76 ppm.
with MgSO4. The volatiles were removed in vacuo, and the residue 13C NMR (126 MHz, CDCl3): δ = 163.3 (t, J = 30.9 Hz), 149.1 (t, J =
was subjected to column chromatography on silica gel to give 2-
(1H-pyrrol-1-yl)aniline. Compound 1m was then prepared as de-
scribed above to give 1m (42 %). 1H NMR (500 MHz, CDCl3): δ =
7.56–7.44 (m, 2 H), 7.42–7.31 (m, 2 H), 7.02 (t, J = 2.2 Hz, 2 H), 6.39
(t, J = 2.2 Hz, 2 H) ppm.
29.5 Hz), 141.6, 134.0, 132.2, 131.9, 130.9, 129.3, 129.3, 125.5 (t, J =
5.4 Hz), 124.2, 124.1, 123.0, 121.9, 115.5 (t, J = 254.4 Hz), 63.1,
14.1 ppm. IR (KBr): ν = 2992, 2955, 2907, 1771, 1571, 1516, 1471,
˜
1366, 1150, 1098, 1019, 945 cm–1
C
. HRMS (ESI): calcd. for
17H12ClF2NO2 [M + H]+ 336.0603; found 336.0598.
General Procedure for Synthesis of 6-Difluoromethyl Phenan-
thridines:[6e,7] A Schlenk tube (10 mL) was loaded with Ag2CO3
(1.25 mmol), NaOAc (1.5 mmol), PhIOAc (1 mmol), K2CO3 (1.5 mmol),
biarylisonitrile (0.5 mmol) and preactivated powdered molecular
sieves (4 Å; 60 mg). TMSCF2CO2Et (2.5 mmol) and 1,4-dioxane (5 mL)
were then added under the protection of N2. The mixture was
stirred at ambient temperature for 24 h. Th reaction was quenched
with water, and the mixture was extracted with ethyl acetate (3 ×
10 mL). The combined organic layers were dried with anhydrous
Na2SO4, and the solvents were evaporated under vacuum. The resi-
due was purified by flash column chromatography on silica gel to
give the desired phenanthridines 3.
Ethyl (8-Acetylphenanthridin-6-yl)difluoroacetate (3e): Purifica-
tion by silica gel chromatography (petroleum ether/EtOAc, 5:1) gave
compound 3e (58 %) as a pale yellow solid. M.p. 129–133 °C. 1H
NMR (500 MHz, CDCl3): δ = 9.05 (d, J = 1.9 Hz, 1 H), 8.63 (d, J =
8.7 Hz, 1 H), 8.51 (dd, J = 7.5, 2.1 Hz, 1 H), 8.38 (dd, J = 8.7, 1.7 Hz,
1 H), 8.11–8.04 (m, 1 H), 7.81–7.71 (m, 2 H), 4.58 (q, J = 7.1 Hz, 2 H),
2.76 (s, 3 H), 1.49 (t, J = 7.1 Hz, 3 H) ppm. 19F NMR (471 MHz, CDCl3):
δ = –98.08 ppm. 13C NMR (126 MHz, CDCl3): δ = 196.9, 163.3 (t, J =
30.8 Hz), 150.4 (t, J = 28.8 Hz), 142.4, 136.6, 135.7, 130.9, 130.2,
129.4, 129.3, 127.4 (t, J = 5.0 Hz), 124.0, 123.0, 122.6, 121.7, 115.5 (t,
J = 254.3 Hz), 63.2, 26.6, 14.1 ppm. IR (KBr): ν = 2990, 2927, 2859,
˜
1771, 1683, 1615, 1528, 1404, 1361, 1298, 1256, 1148, 1095, 1010,
950 cm–1. HRMS (ESI): calcd. for C19H16F2NO3 [M + H]+ 344.1093;
found 344.1091.
Ethyl Difluoro(phenanthridin-6-yl)acetate (3a): Purification by sil-
ica gel chromatography (petroleum ether/EtOAc, 20:1) gave com-
1
pound 3a (70 %) as a pale yellow solid. H NMR (500 MHz, CDCl3):
Ethyl Difluoro-(2-methylphenanthridin-6-yl)acetate (3f): Purifi-
cation by silica gel chromatography (petroleum ether/EtOAc, 50:1)
gave compound 3f (61 %) as a pale yellow solid. 1H NMR (500 MHz,
CDCl3): δ = 8.56 (d, J = 8.1 Hz, 1 H), 8.53–8.49 (m, 1 H), 8.22 (d, J =
6.8 Hz, 1 H), 7.94 (dd, J = 8.4, 2.9 Hz, 1 H), 7.80 (tdd, J = 8.5, 4.0,
1.5 Hz, 1 H), 7.67 (dddd, J = 8.3, 6.9, 3.1, 1.2 Hz, 1 H), 7.50 (dt, J =
8.5, 2.6 Hz, 1 H), 4.59 (dt, J = 7.8, 6.7 Hz, 2 H), 2.61 (s, 3 H), 1.51 (t,
J = 7.1 Hz, 3 H) ppm. 19F NMR (471 MHz, CDCl3): δ = –98.54 ppm.
13C NMR (126 MHz, CDCl3): δ = 163.8 (t, J = 30.6 Hz), 149.1 (t, J =
28.9 Hz), 140.0, 139.0, 133.4, 130.8, 130.6, 130.4, 127.6, 126.0 (t, J =
4.9 Hz), 124.6, 122.3, 122.3 (t, J = 2.0 Hz), 121.5, 116.0 (t, J =
δ = 8.64 (d, J = 8.5 Hz, 1 H), 8.54 (ddt, J = 9.7, 7.6, 2.4 Hz, 2 H),
8.13–8.07 (m, 1 H), 7.87 (ddd, J = 8.3, 7.0, 1.3 Hz, 1 H), 7.78–7.69 (m,
3 H), 4.60 (q, J = 7.1 Hz, 2 H), 1.51 (t, J = 7.1 Hz, 3 H) ppm. 19F NMR
(471 MHz, CDCl3): δ = –98.71 ppm. 13C NMR (126 MHz, CDCl3): δ =
163.7 (t, J = 30.9 Hz), 150.1 (t, J = 29.0 Hz), 141.7, 133.8, 131.2, 130.8,
128.9, 128.8, 127.8, 126.2 (t, J = 4.9 Hz), 124.8, 122.4, 122.2 (t, J =
2.1 Hz), 122.0, 115.8 (t, J = 254.0 Hz), 63.0, 14.1 ppm. IR (KBr): ν =
˜
2993, 1715, 1446, 1364, 1299, 1153, 1099, 1012, 937, 822, 769, 728,
678 cm–1
.
Ethyl Difluoro-(8-methylphenanthridin-6-yl)acetate (3b): Purifi-
cation by silica gel chromatography (petroleum ether/EtOAc, 20:1)
gave compound 3b (50 %) as a pale yellow solid. M.p. 85–89 °C. 1H
NMR (500 MHz, CDCl3): δ = 8.51–8.45 (m, 2 H), 8.35–8.27 (m, 1 H),
8.15–8.04 (m, 1 H), 7.73–7.69 (m, 2 H), 7.68 (dd, J = 8.5, 1.7 Hz, 1 H),
4.61 (q, J = 7.2 Hz, 2 H), 2.61 (s, 3 H), 1.52 (t, J = 7.1 Hz, 3 H) ppm.
19F NMR (471 MHz, CDCl3): δ = –98.83 ppm. 13C NMR (126 MHz,
CDCl3): δ = 163.8 (t, J = 30.8 Hz), 149.8 (t, J = 28.9 Hz), 141.4, 137.9,
132.9, 131.7, 130.7, 128.7, 128.5, 125.4 (t, J = 4.6 Hz), 124.9, 122.4,
122.3, 121.8, 116.0 (t, J = 254.0 Hz), 62.9, 21.9, 14.1 ppm. IR (KBr):
253.7 Hz), 62.9, 22.0, 14.1 ppm. IR (KBr): ν = 2989, 1766, 1446, 1371,
˜
1295, 1153, 1093, 1023, 936, 830, 759, 725, 673 cm–1. HRMS (ESI):
calcd. for C18H16F2NO2 [M + H]+ 316.1144; found 316.1145.
Ethyl (2-Chlorophenanthridin-6-yl)difluoroacetate (3g): Purifica-
tion by silica gel chromatography (petroleum ether/EtOAc, 50:1)
gave compound 3g (69 %) as a pale yellow solid. 1H NMR (500 MHz,
CDCl3): δ = 8.52–8.45 (m, 2 H), 8.42 (d, J = 2.3 Hz, 1 H), 7.99 (d, J =
8.7 Hz, 1 H), 7.85 (ddd, J = 8.3, 7.0, 1.2 Hz, 1 H), 7.73 (ddd, J = 8.3,
7.0, 1.2 Hz, 1 H), 7.64 (dd, J = 8.7, 2.2 Hz, 1 H), 4.57 (q, J = 7.1 Hz, 2
H), 1.48 (t, J = 7.1 Hz, 3 H) ppm. 19F NMR (471 MHz, CDCl3): δ =
–98.71 ppm. 13C NMR (126 MHz, CDCl3): δ = 163.4 (t, J = 30.8 Hz),
150.3 (t, J = 29.1 Hz), 139.9, 135.0, 132.7, 132.1, 131.5, 129.6, 128.5,
126.2 (t, J = 4.9 Hz), 125.8, 122.4, 122.3, 121.7, 115.6 (t, J = 254.1 Hz),
ν = 2986, 2916, 1768, 1449, 1374, 1291, 1152, 1097, 1019, 953, 858,
˜
776, 738 cm–1. HRMS (ESI): calcd. for C18H16F2NO2 [M + H]+
316.1144; found 316.1147.
Ethyl Difluoro-(8-methoxyphenanthridin-6-yl)acetate (3c): Puri-
fication by silica gel chromatography (petroleum ether/EtOAc, 50:1)
gave compound 3c (55 %) as a pale brown solid. 1H NMR (500 MHz,
CDCl3): δ = 8.59 (d, J = 9.1 Hz, 1 H), 8.50 (dd, J = 8.0, 1.6 Hz, 1 H),
8.12–8.06 (m, 1 H), 7.87 (q, J = 2.2 Hz, 1 H), 7.76–7.64 (m, 2 H), 7.53
(dd, J = 9.1, 2.6 Hz, 1 H), 4.56 (q, J = 7.1 Hz, 2 H), 4.01 (s, 3 H), 1.47
(t, J = 7.1 Hz, 3 H) ppm. 19F NMR (471 MHz, CDCl3): δ = –99.95 ppm.
13C NMR (126 MHz, CDCl3): δ = 163.7 (t, J = 31.2 Hz), 158.7, 149.0
(t, J = 28.8 Hz), 140.9, 130.7, 128.8, 128.2, 127.9, 124.9, 124.0, 123.6,
122.2, 121.5, 115.9 (t, J = 253.7 Hz), 105.7 (t, J = 5.1 Hz), 63.0, 55.5,
63.1, 14.1 ppm. IR (KBr): ν = 2991, 2934, 1764, 1605, 1565, 1520,
˜
1483, 1372, 1295, 1154, 1096, 1016, 937 cm–1. HRMS (ESI): calcd. for
C17H13ClF2NO2 [M + H]+ 336.0597; found 336.0594.
Ethyl Difluoro-(3-methoxyphenanthridin-6-yl)acetate (3h): Puri-
fication by silica gel chromatography (petroleum ether/EtOAc, 50:1)
gave compound 3h (52 %) as a pale yellow solid. 1H NMR (500 MHz,
CDCl3): δ = 8.52–8.45 (m, 2 H), 8.40 (d, J = 9.0 Hz, 1 H), 7.81 (ddd,
J = 8.3, 7.0, 1.2 Hz, 1 H), 7.64 (ddd, J = 8.2, 7.0, 1.2 Hz, 1 H), 7.46 (d,
J = 2.7 Hz, 1 H), 7.34 (dd, J = 9.0, 2.7 Hz, 1 H), 4.57 (q, J = 7.1 Hz, 2
H), 3.95 (s, 3 H), 1.46 (t, J = 7.1 Hz, 3 H) ppm. 19F NMR (471 MHz,
CDCl3): δ = –98.75 ppm. 13C NMR (126 MHz, CDCl3): δ = 163.7 (t,
J = 31.1 Hz), 160.2, 150.4 (t, J = 28.6 Hz), 143.4, 134.0, 131.2, 126.7,
126.1 (t, J = 4.8 Hz), 123.2, 121.9, 121.4, 120.0, 118.9, 115.6 (t, J =
14.1 ppm. IR (KBr): ν = 2998, 2928, 2852, 1770, 1617, 1574, 1530,
˜
1457, 1379, 1292, 1224, 1096, 892 cm–1
.
Ethyl (8-Chlorophenanthridin-6-yl)difluoroacetate (3d): Purifica-
tion by silica gel chromatography (petroleum ether/EtOAc, 50:1)
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254.1 Hz), 110.3, 63.0, 55.6, 14.0 ppm. IR (KBr): ν = 2990, 2936, 2844,
gel chromatography (petroleum ether/EtOAc, 50:1) gave compound
3m (26 %) as a dark yellow solid. M.p. 70–71 °C. H NMR (500 MHz,
˜
1
1767, 1615, 1478, 1374, 1302, 1252, 1210, 1095, 1031, 931, 829 cm–1
.
HRMS (ESI): calcd. for C18H16F2NO3 [M + H]+ 332.1093; found CDCl3): δ = 8.04 (dd, J = 2.7, 1.2 Hz, 1 H), 7.97 (dd, J = 8.2, 1.5 Hz,
332.1095.
1 H), 7.87 (dd, J = 8.2, 1.3 Hz, 1 H), 7.63–7.56 (m, 1 H), 7.50–7.40 (m,
1 H), 7.24–7.15 (m, 1 H), 6.96 (dd, J = 4.2, 2.7 Hz, 1 H), 4.48 (q, J =
7.1 Hz, 2 H), 1.41 (t, J = 7.1 Hz, 3 H) ppm. 19F NMR (471 MHz, CDCl3):
δ = –105.83 ppm. 13C NMR (126 MHz, CDCl3): δ = 162.9 (t, J =
31.7 Hz), 146.1 (t, J = 29.5 Hz), 134.1, 130.9, 129.5, 127.8, 125.5,
121.8, 115.2, 114.7, 113.7, 113.0 (t, J = 253.5 Hz), 108.1 (t, J = 3.3 Hz),
Ethyl
Difluoro-(2-trifluoromethylphenanthridin-6-yl)acetate
(3i): Purification by silica gel chromatography (petroleum ether/
EtOAc, 50:1) gave compound 3i (27 %) as a dark red solid. M.p. 93–
95 °C. 1H NMR (500 MHz, CDCl3): δ = 8.89 (s, 1 H), 8.72 (d, J = 8.3 Hz,
1 H), 8.60 (dd, J = 6.4, 4.2 Hz, 1 H), 8.24 (d, J = 8.5 Hz, 1 H), 7.99
(ddd, J = 8.3, 7.0, 1.2 Hz, 1 H), 7.95 (dd, J = 8.6, 1.9 Hz, 1 H), 7.84
(ddd, J = 8.3, 7.1, 1.2 Hz, 1 H), 4.60 (q, J = 7.1 Hz, 2 H), 1.50 (t, J =
7.1 Hz, 3 H) ppm. 19F NMR (471 MHz, CDCl3): δ = –62.08,
–98.95 ppm. 13C NMR (126 MHz, CDCl3): δ = 163.3 (t, J = 30.7 Hz),
152.3 (t, J = 29.3 Hz), 143.0, 133.5, 132.0, 131.7, 130.4 (q, J = 32.7 Hz),
129.1, 128.8, 126.5 (t, J = 4.9 Hz), 125.0 (q, J = 3.4 Hz), 124.5, 124.0
(q, J = 272.7 Hz), 122.5, 119.9 (q, J = 4.3 Hz), 115.4 (t, J = 254.6 Hz),
63.2, 14.0 ppm. IR (KBr): ν = 2925, 2859, 1768, 1612, 1544, 1467,
˜
1374, 1308, 1106, 767, 715 cm–1. HRMS (ESI): calcd. for C15H13F2N2O2
[M + H]+ 291.0940; found 291.0945.
Ethyl [1-(Ethoxycarbonyldifluoromethyl)pyrrolo[1,2-a]quinox-
alin-4-yl]difluoroacetate (3m′): Compound 3m′ was synthesized
in the same way except that the reaction time was 72 h. Purification
by silica gel chromatography (petroleum ether/EtOAc, 50:1) gave
compound 3m′ (34 %) as a bright yellow solid. M.p. 78–81 °C. 1H
NMR (500 MHz, CD2Cl2): δ = 8.23 (d, J = 8.6 Hz, 1 H), 8.07 (dd, J =
8.0, 1.7 Hz, 1 H), 7.72 (ddd, J = 8.8, 7.2, 1.7 Hz, 1 H), 7.62 (ddd, J =
8.2, 7.1, 1.1 Hz, 1 H), 7.31 (d, J = 1.1 Hz, 2 H), 4.51 (q, J = 7.1 Hz, 2
H), 4.42 (q, J = 7.1 Hz, 2 H), 1.42 (dd, J = 7.6, 6.7 Hz, 3 H), 1.30 (t,
J = 7.1 Hz, 3 H) ppm. 19F NMR (471 MHz, CD2Cl2): δ = –93.01,
–105.45 ppm. 13C NMR (126 MHz, CDCl3): δ = 162.9 (t, J = 33.7 Hz),
162.5 (t, J = 31.3 Hz), 145.9 (t, J = 29.5 Hz), 135.1, 131.5, 130.0, 128.0,
126.3, 125.6, 122.4 (t, J = 31.0 Hz), 118.7 (t, J = 6.8 Hz), 116.8 (t, J =
7.8 Hz), 113.0 (t, J = 253.9 Hz), 111.0 (t, J = 247.2 Hz), 107.3 (t, J =
63.1, 14.0 ppm. IR (KBr): ν = 2996, 2949, 1762, 1430, 1368, 1306,
˜
1230, 1175, 1124, 1016, 934 cm–1
. HRMS (ESI): calcd. for
C18H13F5NO2 [M + H]+ 370.0861; found 370.0864.
Ethyl (2,8-Dimethylphenanthridin-6-yl)difluoroacetate (3j): Puri-
fication by silica gel chromatography (petroleum ether/EtOAc, 20:1)
gave compound 3j (54 %) as a pale yellow solid. M.p. 113–116 °C.
1H NMR (500 MHz, CDCl3): δ = 8.42 (d, J = 8.5 Hz, 1 H), 8.26 (s, 1 H),
8.21 (s, 1 H), 7.93 (d, J = 8.3 Hz, 1 H), 7.61 (dd, J = 8.5, 1.7 Hz, 1 H),
7.48 (dd, J = 8.4, 1.8 Hz, 1 H), 4.58 (q, J = 7.1 Hz, 2 H), 2.59 (s, 3 H),
2.57 (s, 3 H), 1.49 (t, J = 7.2 Hz, 3 H) ppm. 19F NMR (471 MHz, CDCl3):
δ = –98.71 ppm. 13C NMR (126 MHz, CDCl3): δ = 163.8 (t, J =
30.9 Hz), 148.7 (t, J = 29.1 Hz), 139.7, 138.9, 137.7, 132.6, 131.3,
130.3, 130.2, 125.3 (t, J = 4.6 Hz), 124.7, 122.5, 122.2, 121.4, 116.1 (t,
3.7 Hz), 64.0, 63.4, 14.0, 13.7 ppm. IR (KBr): ν = 2991, 2924, 2860,
˜
1769, 1622, 1550, 1463, 1380, 1301, 1246, 1110, 1060, 755 cm–1
.
HRMS (ESI-TOF): calcd. for C19H17F4N2O4 [M + H]+ 413.1119; found
413.1124.
J = 253.7 Hz), 62.9, 22.1, 21.8, 14.1 ppm. IR (KBr): ν = 2923, 1715,
˜
1425, 1362, 1222, 1091, 902, 736 cm–1. HRMS (ESI): calcd. for
C19H18F2NO2 [M + H]+ 330.1300; found 330.1302.
Acknowledgments
Ethyl (Benzo[c][2,7]naphthyridin-5-yl)difluoroacetate (3k): Puri-
fication by silica gel chromatography (petroleum ether/EtOAc, 3:1)
gave compound 3k (35 %) as a yellow solid. 1H NMR (500 MHz,
CDCl3): δ = 9.88 (s, 1 H), 8.97 (d, J = 5.8 Hz, 1 H), 8.52 (dd, J = 8.0,
1.4 Hz, 1 H), 8.39 (d, J = 5.7 Hz, 1 H), 8.11 (dd, J = 8.2, 1.4 Hz, 1 H),
7.92–7.71 (m, 2 H), 4.57 (q, J = 7.1 Hz, 2 H), 1.47 (t, J = 7.2 Hz, 3 H)
ppm. 19F NMR (471 MHz, CDCl3): δ = –97.49 ppm. 13C NMR
(126 MHz, CDCl3): δ = 163.0 (t, J = 30.5 Hz), 150.1 (t, J = 29.5 Hz),
150.0, 148.9, 142.8, 138.5, 131.3, 131.0, 129.6, 122.7, 122.5, 117.6,
This work was financially supported by the National Natural Sci-
ence Foundation of China (Nos. 21572128, 21672139) and the
Science Foundation of Shanghai Municipal Commission of Sci-
ences and Technology (No. 15230724800). The authors thank
the Laboratory of Micro-structures of Shanghai University for
structure analysis.
Keywords: Fluorinated compounds · Fluorine · Radicals ·
Cyclization · Isocyanides · Nitrogen heterocycles
115.6, 115.1 (t, J = 254.0 Hz), 63.2, 14.1 ppm. IR (KBr): ν = 2987,
˜
2933, 2866, 1777, 1603, 1569, 1515, 1471, 1414, 1371, 1304, 1155,
1104, 937 cm–1. HRMS (ESI): calcd. for C16H13F2N2O2 [M + H]+
303.0940; found 303.0943.
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Ethyl Difluoro-(8-methyl-thieno[3,2-c]quinolin-4-yl)acetate (3l):
Purification by silica gel chromatography (petroleum ether/EtOAc,
1
3:1) gave compound 3l (21 %) as a yellow solid. M.p. 63–65 °C. H
NMR (500 MHz, CDCl3): δ = 8.09 (d, J = 8.5 Hz, 1 H), 7.93–7.86 (m,
2 H), 7.64 (d, J = 5.4 Hz, 1 H), 7.55 (dd, J = 8.5, 1.9 Hz, 1 H), 4.52 (q,
J = 7.1 Hz, 2 H), 2.63 (s, 3 H), 1.44 (t, J = 7.1 Hz, 3 H) ppm. 19F NMR
(471 MHz, CDCl3): δ = –101.56 ppm. 13C NMR (126 MHz, CDCl3): δ =
163.4 (t, J = 31.6 Hz), 146.9, 145.6 (t, J = 29.9 Hz), 140.3, 139.1, 131.1,
130.5, 128.8, 126.9, 124.7, 123.4 (t, J = 3.9 Hz), 122.3, 114.3 (t, J =
251.9 Hz), 63.1, 21.8, 14.0 ppm. IR (KBr): ν = 2925, 2857, 1771, 1656,
˜
1513, 1458, 1380, 1280, 1177, 1106, 1024, 827, 744 cm–1. HRMS
(ESI): calcd. for C16H14F2NO2S [M + H]+ 322.0708; found 322.0711.
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Ethyl Difluoro(pyrrolo[1,2-a]quinoxalin-4-yl)acetate (3m): Com-
pound 3m was synthesized in the same way, except that 1-(2-iso-
cyano-phenyl)-1H-pyrrole (1m; 1.0 mmol,
2
equiv.) and
TMSCF2CO2Et (2; 0.5 mmol, 1 equiv.) were used. Purification by silica
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.
Received: April 5, 2017
Eur. J. Org. Chem. 2017, 3145–3151
www.eurjoc.org
3151
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim