Boron-Catalyzed Azide Insertion of α-Aryl α-Diazoesters

Article abstract of DOI:10.1021/acs.joc.8b03278

A challenging metal-free azide insertion of α-aryl α-diazoesters in the presence of B(C₆F₅)₃ (5 mol %) was developed for the first time. The reaction features an easy operation, wide substrate scope, and mild conditions an

Full text of DOI:10.1021/acs.joc.8b03278

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Boron-Catalyzed Azide Insertion of #-Aryl #-Diazoesters
HTET HTET SAN, Chun-Ying Wang, Hai-Peng Zeng, Shi-Tao Fu, Min Jiang, and Xiang-Ying Tang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b03278 • Publication Date (Web): 11 Mar 2019
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Boron-Catalyzed Azide Insertion of α-Aryl α-Diazoesters
Htet Htet San,† Chun-Ying Wang,† Hai-Peng Zeng,† Shi-Tao Fu,† Min Jiang‡ and
Xiang-Ying Tang*,†
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†School of Chemistry and Chemical Engineering and Hubei Key Laboratory of
Bioinorganic Chemistry and Materia Medica, Huazhong University of Science
and Technology, 1037 Luoyu Road, Wuhan 430074, People’s Republic of China
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‡Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic
Chemistry (SIOC), Chinese Academy of Sciences, 345 Lingling Road, Shanghai
200032, People’s Republic of China
ABSTRACT: A challenging metal-free azide insertion of α-aryl α-diazoesters in the
presence of B(C6F5)3 (5 mol %) was developed for the first time. The reaction features
easy operation, wide substrate scope, mild condition and affording the corresponding
products in moderate to high yields. More importantly, alkene and alkyne functional
groups were well tolerated because no cyclopropanation or cyclopropenation was
observed. Furthermore, the corresponding azide products could be converted to
primary amines or 1,2,3-triazole derivatives after simple transformations.
R3
N
N2
N3
N
TMSN3
B(C6F5)3
N
CuAAC
CO2R2
CO2R2
R1
R1
26 examples, up to 85% yields
CO2R2
R1
mild conditions
metal-free
alkene tolerated alkyne tolerated
α-Diazo compounds are useful reactive substrates which can undergo a series of
useful transformations, such as metal catalyzed cycloadditions with unsaturated
double or triple bonds, insertion reactions with C-H or X-H bonds, carbene migratory
insertions, and other related reactions.1-2 Recently, catalytic transformations of diazo
compounds under metal free conditions, including the organocatalysis and
enzyme-catalysis, have also been intensively investigated.3 On the other hand, the
azide anion serves as a strong nucleophile and provide one of the most powerful
methods for introducing nitrogen atoms into organic molecules.4 To this regard, the
development of a practical azide insertion into α-diazoesters is highly desirable and
should have broad applications in organic synthesis. Even though transition-metal
catalyzed CF3, OCF3, SCF3 and CN insertions of α-diazoesters5 were well established
(Scheme 1, a-d), the azide insertion of diazo compounds remain a challenge, probably
due to the degradation of azide through nitrene intermediate under metal-catalysis.
Therefore, a metal free process might be an alternative choice.
Scheme 1. Transition metal and BCF catalyzed insertions of α-diazoesters
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(a) Copper-catalyzed trifluoromethylation: ref.: 5a-b
N2
CF3
TMSCF3
CO2R2
CO2R2
R1
R1
Cu(I)
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(b) Copper-or Rhodium-catalyzed trifluoromethylthiolation: ref.: 5e-g
N2
SCF3
CO2R2
CuSCF3 or Me4NSCF3
CO2R2
R1
R1
Cu(I) or Rh(II)
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Silver-catalyzed trifluoromethoxylation: ref.: 5h
N2
(c)
OCF3
CO2R2
AgOCF3 or AgF/CF3SO3CF3
CO2R2
R1
R1
(d) Copper-catalyzed hydrocyanation: ref.: 5i
N2
CN
CO2R2
OH
NC
CO2R2
R1
R1
Cu(I)
(e) This work: BCF-catalyzed azide insertion
N2
N3
B(C6F5)3
CO2R2
CO2R2
R1
R1
TMSN3
Tris(pentafluorophenyl)-borane,
B(C6F5)3
(BCF),
and
other
related
electron-deficient boron catalysts, have been recently investigated intensively for their
useful applications in organic synthesis, including reduction of unsaturated
substances,6
dehydrogenations,7
hydrosilylations,8
hydroaminations,9
hydroborations,10 dehydrogenative cross couplings,11 polymerizations12 and other
.
reactions.13 Moreover, B(C6F5)3 H2O has also been demonstrated as versatile Brønsted
acid catalyst.14 For example, the group of Moran have developed a catalytic method
for challenging azidation of tertiary aliphatic alcohols. The group of Shibuya also has
reported an interesting double hydrofunctionalization of unactivated alkynes.
Meanwhile, in FLP (Frustrated Lewis Pair) chemistry pioneered by Stephan and
Erker,15 BCF has also been most frequently used as the Lewis acid component.16
Interestingly, recent investigations have shown that BCF possesses some unique
properties in insertion reactions of α-diazoesters. The group of Prof. Zhang has
reported a novel chemoselective ortho-C-H functionalization of phenols with α-aryl
α-dizaoesters.17 We also developed an O−H Bond insertion of α-aryl α-dizaoesters
using water as the solvent.18 Inspired by the above studies and based on the basis of
our research in carbene chemistry, we envisioned that BCF may catalyzed the azide
insertion of α-aryl α-dizaoesters (Scheme 1, e).
We first test the reaction of α-diazoesters 1a and TMSN3 (1 equiv) in the presence
of B(C6F5)3 (5 mol %) in anhydrous DCM at room temperature. The reaction afforded
the desired product 2a in 56% yield along with the water insertion byproduct in 18%
yield (Table 1, entry 1). The yield of 2a increased to 71% and 80% when 2 or 3 equiv
of TMSN3 was added (Table 1, entries 2 and 3). In the absence of BCF catalyst, no
desired product was formed (Table 1, entry 4). When firstly cooled to 0 ℃ and then
slowly warmed to room temperature, the reaction gave the corresponding azide
insertion product 2a in 82% yield (Table 1, entry 5). Further studies uncovered that
the reaction was sensitive to concentration. When performing the reactions in 1 mL,
0.5 mL and 100 µL of anhydrous DCM, 2a was delivered in 63% to 40% yields
respectively (Table 1, entries 6-8). To suppress the formation of the water-insertion
byproduct, 4 Å molecular sieves were added, 2a was produced in 85% yield and only
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trace amount of water insertion product was observed (Table 1, entry 9). A solvent
screen showed that DCM is the best solvent for this transformation (Table 1, entries
10-14). Decreasing the loadings of catalyst, the reactions furnished product 2a in 50%
and 73% yields, respectively (Table 1, entries 15 and 16). When 10 mol% of the
catalyst was used, the yield of 2a was not increased (Table 1, entry 17). While
Rh2(OAC)4 was employed as catalyst, the reaction only produced 2a in less than 10%
yield (Table 1, entry 18). Finally, when 1a and BCF were mixed together for 40 min
to remove water first,17 then treated with TMSN3, the reaction could give 2a in 59%
yield. This result confirmed that BCF is the real catalyst instead of BCF.H2O (Table 1,
entry 19).
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Table 1. Screening of the Reaction Conditionsa
N3
TMSN3 (y equiv)
N2
OH
OEt
B(C6F5)3 (x mol %)
OEt
OEt
+
Ph
solvent (2 mL), 0 oC-rt
4 Å MS
O
O
O
2a
1a
entry
1d
x
5
5
5
solvents
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
THF
y
1
time (h)
yield of 2a (%)b,c
56 (18)
2
2d
3d
2
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
2
71 (12)
2
80 (10)
4d
5
-
24
2
N.R.
e
5
5
5
5
5
5
5
5
5
1
82 (8)
6f
2
63 (12)
7g
2
58 (12)
8h
9i
2
40 (15)
2
85 (trace)
34 (trace)
32 (11)
10
12
24
24
24
4
Hexane
PhCl
13
32 (12)
14
15
Toluene
DCM
DCM
DCM
DCM
DCM
70 (10)
2
50 (14)
16
17
3
10
5
5
2
73 (12)
1.5
2
85 (trace)
10 (trace)
59 (10)
18j
19k
2
a0.2 mmol scale. bIsolated yields. cYields of water insertion product were shown
d
f
in the parenthesis. Room temperature. eNo catalyst was added. With 1 mL of
g
h
i
solvent. with 0.5 mL of solvent. with 0.1 mL of solvent. 4 Å MS was used.
jRh2(OAC)4 was used as catalyst. 1a and BCF were stirred for 40 min at 0 C,
k
o
then TMSN3 was added. THF = tetrahydrofuran. DCM = dichloromethane.
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With the best reaction conditions in hand (Table 1, entry 9), we next tried our
efforts to determine the generality of the reaction (Scheme 2). Substrates 1 bearing
para-substituents were all suitable for this reaction and gave corresponding products
2b−2i in moderate to good yields. The reactions of meta-substituted substrates also
delivered desired products 2j−2m in moderate yields. It was found that
ortho-substituted diazoesters were compatible with the reaction conditions and the
azide insertion products 2n and 2o were obtained in relatively lower yields, probably
due to the steric hindrance. As for dichlor-substituted diazoester, product 2p was
obtained in 69% yield. Naphthyl, thienyl and dioxole groups were also tolerated in
this reaction, producing products 2q, 2r and 2s in 59%, 55% and 74% yields.
Changing the ethyl group of the diazoesters to isopropyl, benzyl, methyl and isopentyl
groups, corresponding products 2t−2w were delivered in 68-75% yields. In addition,
upon conducting the reaction of 1a on a 1.0 mmol scale, the desired product 2a could
still be obtained in 78% yield.
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Scheme 2. Substrate Scopea
N2
N3
OEt
OEt
B(C6F5)3 (5 mol %)
TMSN3
R
R
DCM (2 mL), 0 oC-rt
4Å MS
O
O
1
2
N3
2f
R = C6H5, 2 h, , 70%
2b
R = F, 5 h, , 60%
OEt
OEt
2c
R = Cl, 3.5 h, , 73%
2d
R = MeO, 4 h, , 78%
2e
R = Me, 4 h, , 80%
R = TBDMSO, 2 h, 2g, 68%
2h
R = EtO2C, 5 h, , 81%
O
R
2i
R = BnO, 24 h, , 65%
OMe N3
Cl
N3
N3
2j
R = Cl, 5 h, , 67%
2k
R = F, 6 h, , 50%
OEt
OMe
Cl
2l
R = Me, 4.5 h, , 64%
O
O
O
2m
R = MeO, 7 h,
, 74%
2n
8 h, , 43%
2o
5 h, , 44%
N3
N3
N3
N3
N3
Cl
Cl
OEt
OEt
OEt
OEt
OiPr
O
O
O
O
O
O
O
S
2p
2q
5 h, , 59%
2r
1:5 h, , 55%
2s
3 h, , 74%
2t
5 h, , 69%
4:5 h, , 72%
N3
N3
N3
N3
OMe
OBn
O
OEt
O
O
O
O
tBu
c
2u
4 h, , 70%
2v
4 h, , 68%
2w
5 h,
, 75%
2a,
6 h,
78%
a0.2 mmol scale. bIsolated yields. c1.0 mmol scale
Moreover, alkene and alkyne substituted substrates were well tolerated to provide
corresponding products 2aa, 2ab and 2ac in 85%-70% yields respectively (Scheme
3), further demonstrating the unique property of this boron-catalyst as compared to
transition metal.
Scheme 3. Reactions of alkyene/alkyne containing α-diazoester a,b
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N3
N2
TMSN3
O
O
O
(1)
(2)
Standard condition
O
O
, 2aa
8 h
, 70%
O
N3
N2
TMSN3
Standard condition
O
O
, 2ab
4 h
, 85%
O
N3
N2
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O
O
TMSN3
Standard condition
O
O
O
(3)
O
O
, 2ac
6 h
, 70%
a0.2 mmol scale. bIsolated yields.
Click chemistry has been intensively investigated in medicinal chemistry, material
chemistry and life science.19 Therefore, the azide products were converted into
triazoles in a one-pot manner. As summarized in scheme 4, the desired triazole
products 3a-3f were obtained in 50-75% yields.
Scheme 4. One-Pot Synthesis of 1,2,3-Triazolesa
Ph
N2
1. B(C6F5)3 (5 mol %)
DCM, 0 oC-rt, Ar
N
OEt
N
N
+
TMSN3
3 equiv
R
O
2. Phenylacetylene (1 equiv)
CuTc (2 mol %), toluene
OEt
1
R
85 oC, 3 h
O
0.2 mmol
3
OEt
OEt
OEt
O
O
O
O
O
Br
Me
3d
, 66%
5 h,
N
3b
4 h, , 50%
3c
4 h, , 63%
3a
, 65%
3 h,
OiPr
Ph
OBn
O
N
O
N
3f
4 h, , 65%
3e
5 h, , 60%
a0.2 mmol scale. bIsolated yields. CuTc = copper(I) thiophene-2-carboxylate.
A Staudinger reduction was performed and free α-amino acid 4a was obtained in
78% yield from 2a (Scheme S1, a).20 Encouraged by this result, a one-pot version of
this transformation was developed and 4a could still be formed in 68% yield from 1a
(Scheme S1, b).
To gain more mechanistic insight into this reaction, several NMR experiments
were carried out (see Figure S1 in SI). In the 19F NMR spectra, all three peaks of BCF
shifted to downfield, but not identical with anhydrous B(C6F5)3 after 1-3 equiv of
1a was added, indicating the coordination of 1a with BCF after water was consumed
(Figure S1, 1-4). However, after 1 equiv of TMSN3 was added, the set of para and
meta peaks shifted to up-field, indicating that BCF may have interactions with both 1a
and TMSN3 (Figure S1, 5).21
14b
On the basis of reported literature17 and the above experimental observations, a
plausible reaction mechanism is shown in Scheme 5. First, anhydrous BCF is
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generated after the trace amount of water was consumed via water insertion with 1.18
Then, BCF can coordinate with diazo-compounds, and meanwhile, TMSN3 was also
activated by the carbonyl group. Finally, nucleophilic attack of TMSN3 to
diazo-compounds 1 furnish silyl enol ether intermediate, which is a pair of E/Z
isomers as confirmed by 1H and 13C NMR (See Figure S5 and S6 in SI). Finally, after
hydrolysis (silica gel chromatography), the silyl enol ether is converted to the desired
products 2.
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Scheme 5. Plausible mechanism
N2
B
F
N
N
OEt
Ar
N3
N3
1
O
+
B(C6F5)
OEt
OEt
OEt
Ar
N3
Ar
Ar
O
TMSN3
OSiMe3
O
2
Si
Me3
confirmed by 1H NMR
In conclusion, we have developed a novel B(C6F5)3 catalyzed protocol for the
insertion of α-diazoesters for facile synthesis of α-azide ester derivatives under mild
conditions. Compared to Rh2(OAc)4, BCF catalyzed azide inserstion of α-diazoesters
was more efficient and no azide degradation was observed. Significantly, alkene and
alkyne groups were well tolerated, thus avoiding cyclopropanation22 or other
transformations2d when transition-metal catalysts were used. Further investigations of
BCF-catalyzed insertion reactions of α-diazoesters is currently underway in our
group.
EXPERIMENTAL SECTION
1. General Remarks: All air and moisture-sensitive manipulations were carried out
with standard Schlenk techniques under nitrogen. 1H and 13C {1H} NMR spectra were
measured at 400 MHz and 100 MHz in CDCl3. Data for 1H NMR spectra are reported
as follows: chemical shift (ppm, referenced to TMS; s = singlet, d = doublet, t =
triplet, dd = doublet of doublets, dt = doublet of triplets, m = multiplet), coupling
constant (Hz), and integration. Data for 13C {1H} NMR is reported in terms of
chemical shift (ppm) relative to residual solvent peak (CDCl3: 77.0 ppm). The HRMS
analysis was obtained on a GC-TOF mass spectrometer. Infrared spectra were
recorded on a Perkin-Elmer PE-983 spectrometer with absorption in cm-1. THF and
toluene were distilled from sodium and benzophenone prior to be used. DCE and
DCM were distilled from CaH2 prior to be used. All reactions were monitored by
TLC with Huanghai GF254 silica gel coated plates. Flash column chromatography
was carried out using 300-400 mesh silica gel at increased pressure.
Control Experiments:
1
.
19F- and H-NMR titration experiments of 1a with B(C6F5)3 nH2O in toluene-d8:
BCF (10.0 mg, 1 equiv) was added into an NMR tube, followed by 0.6 mL toluene-d8.
For the following each step, NMR was tested. Step 1, 1a (4.0 mg, 1 equiv) was then
added; Step 2, another 4.0 mg of 1a (1 equiv) was added; 12.0 mg of 1a (3 equiv) was
added; Step 4, 6 µL of TMSN3 (1 equiv) was added.
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Control IR experiments: First, the IR of pure TMSN3 was tested. Second step, 25
mol% of BCF (12.8 mg) and TMSN3 (11.5 mg, 0.1 mmol) were mixed in DCM (1
mL) and the mixture was subjected to IR. Third step, diazo compound 1a (19 mg, 0.1
mmol) was added and the resulting mixture was checked by IR. It was shown that the
characteristic peak of TMSN3 at 2131 cm-1 disappeared after BCF was added and
appeared again when 1a was added, indicating 1a has a stronger interaction with BCF
than TMSN3.
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General Procedure for Synthesis of 1.5a To a mixture of esters (1.0 equiv) and
p-toluenesulfonyl azide (TsN3) (1.2 equiv) in anhydrous acetonitrile (3 mL/mmol),
DBU (1.4 equiv) was added. The reaction mixture was stirred at room temperature for
overnight. Upon the complete consumption of the starting materials, the reaction
mixture was diluted with appropriate water, followed by extraction with ethyl acetate.
After washing with 10% NH4Cl solution and brine, the combined organic extracts
were dried over Na2SO4 and concentrated by rotary evaporation. The residue was
purified by flash chromatography (petroleum ether/ethyl acetate = 100/1 to 50/1) to
give 1.
Synthesis of Ethyl 2-diazo-2-(4-((tert-butyldimethylsilyl)oxy)phenyl)acetate 1g. The
mixture of ethyl 2-(4-hydroxyphenyl)acetate (3.604 g, 20.0 mmol, 1.0 equiv),
TBDMSCl (3.316 g, 22.0 mmol, 1.1 equiv) and imidazole (2.723 g, 40.0 mmol, 2.0
equiv) in dry DMF (20 mL) was stirred under argon atmosphere until the complete
conversion. The mixture was then added into 1M NaOH solution and extracted with
ethyl acetate and the organic layer was collected and washed consecutively with H2O,
brine and the combined organic extracts were dried over Na2SO4 and concentrated by
rotary evaporation. The residue was purified by flash chromatography (petroleum
ether/ethyl acetate = 10/1) to get the protected phenol in 80% yield (4.711 g).23
The next step was followed by the general procedure for synthesis of 1, 1 mmol scale.
Isolated yield: (deep orange oil; 218.0 mg, 68% yield).
Synthesis of Ethyl 2(4-benzyloxy) phenyl)-2-diazoacetate 1i. A mixture of ethyl
2-(4-hydroxyphenyl)acetate (1.802 g, 10 mmol,1.0 equiv), K2CO3 (2.764 g, 20 mmol,
2.0 equiv) and BnBr (1.881 g, 11 mmol, 1.1 equiv) was stirred in DMF (10 mL)
solvent at room temperature for 16 hr. Then the reaction was diluted with water and
extracted with ethyl acetate. After washing with brine solution, the combined organic
extracts were dried over Na2SO4 and concentrated by rotary evaporation. The residue
was purified by flash chromatography (petroleum ether/ethyl acetate = 10:1) to afford
the protected intermediate as a clear oily liquid (2.108g, 78%) yield.24
The next step was followed by the general procedure for synthesis of 1. 3 mmol scale.
Isolated yield: (Orange oil; 596.0 mg, 67% yield).
General procedure for Synthesis of 2-azido-2-arylacetates 2. To a solution of
B(C6F5)3 (5.0 mg, 5 mol %) in anhydrous DCM (1 mL) was added TMSN3 (79.8 µL,
3 equiv, 0.6 mmol) under argon atmosphere. The reaction mixture was then cooled
down to 0 ℃. Then, diazo compounds 1 (0.2 mmol) in anhydrous DCM (1 mL) was
added dropwise with via a syringe over a period of 10 mins. After completion
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(checked by TLC), the mixture was concentrated and purified by flash
chromatography (PE/EA = 50:1 to 20:1) afforded the desired product 2.
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Procedure for the 1 mmol Scale Synthesis of α-azido phenyl ester 2a. To a 25
mL reaction tube equipped with a magnetic stir bar were added B(C6F5)3 (25.0 mg, 5
mol %) and TMSN3 (395.0 µL, 3 equiv, 3 mmol) in anhydrous DCM (5 mL) under
argon atmosphere. The reaction mixture was then cooled down to 0 ℃ by ice bath.
After cooling to 0 ℃, diazo compound (190.2 mg, 1 mmol) in anhydrous DCM (5
mL) was added dropwise with via syringe. After completion (checked by TLC), the
mixture was concentrated and purified by flash chromatography (PE/EA = 50:1 to
20:1) afforded the desired product 2a in (160.0 mg, 78%) yield.
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General procedure for Synthesis of 3. To a solution of B(C6F5)3 (5.0 mg, 5 mol
%) in anhydrous DCM (1 mL) was added TMSN3 (79.8 µL, 0.6 mmol, 3 equiv) under
argon atmosphere. The reaction mixture was then cooled down to 0 ℃. Then, diazo
compound (38.0 mg, 0.2 mmol) in anhydrous DCM (1 mL) was added dropwise with
via syringe over a period of 10 mins. After completion (checked by TLC), the mixture
was concentrated by rotary evaporation. The residue was then treated with
phenylacetylene (1 equiv) and CuTc (2 mol %) in toluene. The reaction mixture was
stirred at indicated temperature. Upon the complete, the reaction mixture was
concentrated under reduced pressure and purified by flash chromatography (PE/EA =
5:1) to afford desired product 3.
General procedure for Synthesis of 4. To a solution of B(C6F5)3 (5.0 mg, 5 mol
%) in anhydrous DCM (1 mL) was added TMSN3 (79.8 µL, 0.6 mmol, 3 equiv) under
argon atmosphere. The reaction mixture was then cooled down to 0 ℃. Then, diazo
compound (38.0 mg, 0.2 mmol) in anhydrous DCM (1 mL) and added dropwise with
via a syringe over a period of 10 mins. After completion (checked by TLC), the
mixture was concentrated by rotary evaporation. PPh3 (78.6 mg, 0.3 mmol, 1.5 equiv)
in THF/H2O (10:1) was added. The reaction mixture was stirred at room temperature
for 12 h. After completion (checked by TLC), the reaction mixture was concentrated
under reduced pressure. The residue was purified by preparative TLC (PE/EtOAc =
2/1) to give 4.
Procedure for deuterium labeling experiment. To a solution of B(C6F5)3 (5.0
mg, 5 mol %) in anhydrous DCM (1 mL) was added TMSN3 (79.8 µL, 3 equiv, 0.6
mmol) and D2O (9.0 µL, 2.5 equiv) under argon atmosphere. The reaction mixture
was then cooled down to 0 ℃ . Then, diazo compound (38.0 mg, 0.2 mmol) in
anhydrous DCM (1 mL) was added dropwise with via a syringe over a period of 10
mins. After completion (checked by TLC), the mixture was concentrated and purified
by flash chromatography (PE/EA = 50:1 to 20:1) to give the desired product 2a-d (28
mg, 68% yield), which was then subjected to 1H NMR test. Ethyl
2-azido-2-Phenylacetate 2a-d, (D contain = 75%). Colorless oil; 28 mg, 68% yield;
1H NMR (400 MHz, CDCl3): δ 7.41 (s, 4H), 4.95 (s, 0.25H), 4.32-4.17 (m, 2H), 1.26
(t, J = 7.2 Hz, 3H).
Ethyl 2-azido-2-phenylacetate (2a), known compound.25 Colorless oil; 35.0 mg, 85%
1
yield; H NMR (400 MHz, CDCl3): δ 7.41-7.39 (m, 5H), 4.94 (s, 1H), 4.30-4.19 (m,
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2H), 1.26 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 169.1, 134.0,
129.2, 129.1, 127.6, 65.3, 62.1, 14.0.
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Ethyl 2-azido-2-(4-fluorophenyl)acetate (2b), unknown compound. Colorless oil; 27.0
mg, 60% yield; 1H NMR (400 MHz, CDCl3): δ 7.38 (dd, J = 5.2 Hz, 8.4 Hz, 2H), 7.10
(dd, J = 8.6, 8.6 Hz, 2H), 4.95 (s, 1H), 4.29-4.21 (m, 2H), 1.26 (t, J = 7.2 Hz, 3H);
13C{1H} NMR (100 MHz, CDCl3): δ 168.9, 163.1 (d, J = 247.3 Hz), 129.9 (d, J = 3.2
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Hz), 129.5 (d, J = 8.4 Hz), 116.1 (d, J = 21.7 Hz), 64.6, 62.3, 14.0; F NMR (376
MHz, CDCl3 ) δ -111.87 ~ -111.95 (m); IR (KBr): ѵ 3078, 2986, 2939, 2109, 1897,
1744, 1605, 1511 cm-1. HRMS (ESI) m/z: [M + Na]+ calcd. for C10H10FN3O2Na
246.0649, found: 246.0652.
Ethyl 2-azido-2-(4-chlorophenyl)acetate (2c), unknown compound. Colorless oil; 35.0
mg, 73% yield; 1H NMR (400 MHz, CDCl3): δ 7.39 (d, J = 8.4 Hz, 2H), 7.34 (d, J =
8.0 Hz, 2H), 4.95 (s, 1H), 4.27-4.22 (m, 2H), 1.26 (t, J = 7.2 Hz, 3H); 13C{1H} NMR
(100 MHz, CDCl3): δ 168.7, 135.3, 132.5, 129.3, 128.9, 64.6, 62.4, 14.0. IR (KBr): ѵ
2985, 2933, 2110, 1744, 1596, 1493, 1200, 1023 cm-1. HRMS (ESI) m/z: [M + Na]+
calcd. for C10H10ClN3O2Na 262.0354, found: 262.0356.
Ethyl 2-azido-2-(4-methoxyphenyl)acetate (2d), known compound.26 Colorless oil;
36.4 mg, 78% yield; 1H NMR (400 MHz, CDCl3): δ 7.32 (d, J = 8.4 Hz, 2H), 6.93 (d,
J = 8.4 Hz, 2H), 4.89 (s, 1H), 4.31-4.16 (m, 2H), 3.82 (s, 3H), 1.26 (t, J = 7.2 Hz,
3H); 13C{1H} NMR (100 MHz, CDCl3) δ 169.3, 160.2, 128.9, 125.9, 114.4, 64.8,
62.0, 55.3, 14.0.
Ethyl 2-azido-2-(p-tolyl)acetate (2e), unknown compound. Colorless oil; 35.0 mg,
1
80% yield; H NMR (400 MHz, CDCl3): δ 7.27 (d, J = 8.0 Hz, 2H), 7.21 (d, J = 8.0
Hz, 2H), 4.90 (s, 1H), 4.01-4.16 (m, 2H), 2.36 (s, 3H), 1.25 (t, J = 7.2 Hz, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 169.2, 139.2, 130.9, 129.7, 127.5, 65.1, 62.0,
21.2, 14.0. IR (KBr): ѵ 2961, 2929, 2861, 2106, 1743, 1611, 1463, 1269 cm-1. HRMS
(ESI) m/z: [M + Na]+ calcd. for C11H13N3O2Na 242.0900, found: 242.0902.
Ethyl 2-([1,1'-biphenyl]-4-yl)-2-azidoacetate (2f), unknown compound. Colorless oil;
39.4 mg, 70% yield; 1H NMR (400 MHz, CDCl3): δ 7.63 (d, J = 7.8 Hz, 2H), 7.58 (d,
J = 7.8 Hz, 2H), 7.47-7.42 (m, 4H), 7.38-7.34 (m, 1H), 4.99 (s, 1H), 4.34-4.19 (m,
2H), 1.28 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 169.1, 142.1,
140.1, 132.8, 128.8, 128.0, 127.7, 127.6, 127.1, 65.1, 62.2, 14.0. IR (KBr): ѵ 3060,
3032, 2984, 2936, 2107, 1743, 1604, 1566 cm-1. HRMS (ESI) m/z: [M + Na]+ calcd.
for C16H15N3O2Na 304.1056, found: 304.1058.
Ethyl 2-azido-2-(4-((tert-butyldimethylsilyl)oxy)phenyl)acetate (2g), unknown
compound. Colorless oil; 45.3 mg, 68% yield; 1H NMR (400 MHz, CDCl3): δ 7.24 (d,
J = 8.4 Hz, 2H), 6.85 (d, J = 8.4 Hz, 2H), 4.87 (s, 1H), 4.26-4.21 (m, 2H), 1.25 (t, J =
13
7.2 Hz, 3H), 0.98 (s, 9H), 0.21 (s, 6H); C{1H} NMR (100 MHz, CDCl3) δ 169.3,
156.5, 128.9, 126.6, 120.5, 64.9, 62.0, 25.6, 18.1, 14.0, -4.5. IR (KBr): ѵ 3038, 2957,
2934, 2894, 2860, 2106, 1745, 1511 cm-1. HRMS (ESI) m/z: [M + Na]+ calcd. for
C16H25N3O3SiNa 358.1557, found: 358.1561.
Ethyl 4-(1-azido-2-ethoxy-2-oxoethyl)benzoate (2h), unknown compound. Colorless
oil; 45.0 mg, 81% yield; 1H NMR (400 MHz, CDCl3): δ 8.09 (d, J = 8.0 Hz, 2H), 7.48
(d, J = 8.0 Hz, 2H), 5.04 (s, 1H), 4.39 (q, J = 6.8 Hz, 2H), 4.27-4.23 (m, 2H), 1.39 (t,
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J = 6.8 Hz, 3H), 1.25 (t, J = 6.8 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 168.5,
165.8, 138.6, 131.3, 130.2, 127.5, 64.9, 62.3, 61.2, 14.2, 14.0. IR (KBr): ѵ 2984,
2939, 2907, 2110, 1744, 1612, 1578, 1279 cm-1. HRMS (ESI) m/z: [M + Na]+ calcd.
for C13H15N3 O4Na 300.0955, found: 300.0958.
Ethyl 2-azido-2-(4-(benzyloxy)phenyl)acetate (2i), unknown compound. Colorless oil;
40.2 mg, 65% yield; 1H NMR (400 MHz, CDCl3): δ 7.44-7.37 (m, 4H), 7.35-7.30 (m,
3H), 6.99 (d, J = 8.4 Hz, 2H), 5.07 (s, 2H), 4.89 (s, 1H), 4.29-4.17 (m, 2H), 1.25 (t, J
= 7.2 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 169.3, 159.4, 136.6, 129.0,
128.6, 128.1, 127.5, 126.2, 115.3, 70.1, 64.8, 62.0; IR (KBr): ѵ 3066, 3035, 2984,
2936, 2872, 2106, 1887, 1742 cm-1; HRMS (ESI) m/z: [M + Na]+ calcd. for
C17H17N3O3Na 334.1162, found: 334.1166.
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Ethyl 2-azido-2-(3-chlorophenyl)acetate (2j), unknown compound. Colorless oil; 32.0
mg, 67% yield; 1H NMR (400 MHz, CDCl3): δ 7.40-7.33 (m, 3H), 7.29-7.26 (m, 1H),
13
4.94 (s, 1H), 4.31-4.30 (m, 2H), 1.27 (t, J = 7.2 Hz, 3H); C{1H} NMR (100 MHz,
CDCl3): δ 168.5, 135.9, 134.9, 130.3, 129.4, 127.8, 125.6, 64.7, 62.4, 14.0. IR (KBr):
ѵ 3067, 2985, 2936, 2110, 1744, 1577, 1477, 1333 cm-1. HRMS (ESI) m/z: [M + Na]+
calcd. for C10H10ClN3O2Na 262.0354, found: 262.0357.
Ethyl 2-azido-2-(3-fluorophenyl)acetate (2k), unknown compound. Colorless oil; 22.4
1
mg, 50% yield; H NMR (400 MHz, CDCl3): δ 7.42-7.36 (m, 1H), 7.18 (d, J = 7.6
13
Hz, 1H), 7.13-7.08 (m, 2H), 4.99 (s, 1H), 3.80 (s, 3H); C{1H} NMR (100 MHz,
CDCl3): δ 169.0, 162.9 (d, J = 246.4 Hz), 136.1 (d, J = 7.2 Hz), 130.7 (d, J = 8.2 Hz),
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123.3 (d, J = 3.0 Hz), 116.4 (d, J = 21.0 Hz), 114.7 (d, J = 22.7 Hz), 64.7, 53.1; F
NMR (376 MHz, CDCl3 ) δ -111.24 ~ -111.30 (m). IR (KBr): ѵ 3070, 2958, 2851,
2111, 1749, 1594, 1450, 1264 cm-1. HRMS (ESI) m/z: [M + Na]+ calcd for
C9H8FN3O2Na 232.0493; found: 232.0495.
Ethyl 2-azido-2-(m-tolyl)acetate (2l), unknown compound. Colorless oil; 28.0 mg,
64% yield; 1H NMR (400 MHz, CDCl3): δ 7.32-7.28 (m, 1H), 7.21-7.17 (m, 3H), 4.90
(s, 1H), 4.32-4.17 (m, 2H), 2.38 (s, 3H), 1.26 (t, J = 7.2Hz, 3H); 13C{1H} NMR (100
MHz, CDCl3) δ 169.2, 138.9, 133.8, 130.0, 128.9, 128.3, 124.7, 65.3, 62.1, 21.4, 14.0.
IR (KBr): ѵ 2983, 2928, 2868, 2108, 1744, 1608, 1464, 1189 cm-1. HRMS (ESI) m/z:
[M + Na]+ calcd for C11H13N3O2Na 242.0900, found: 242.0902.
Ethyl 2-azido-2-(3-methoxyphenyl)acetate (2m), unknown compound. Colorless oil;
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35.0 mg, 74% yield; H NMR (400 MHz, CDCl3): δ 7.32 (dd, J = 8.4, 8.4 Hz, 1H),
6.98-6.92 (m, 3H), 4.91 (s, 1H), 4.12-4.17 (m, 2H), 3.82 (s, 3H), 1.26 (t, J = 7.2 Hz,
13
3H); C{1H} NMR (100 MHz, CDCl3) δ 168.9, 159.9, 135.3, 130.1, 119.8, 114.9,
113.0, 65.2, 62.1, 55.3, 14.0. IR (KBr): ѵ 2983, 2941, 2839, 2109, 1743, 1604, 1463,
1266 cm-1. HRMS (ESI) m/z: [M + Na]+ calcd. for C11H13N3O3Na 258.0849, found:
258.0852.
Ethyl 2-azido-2-(2-methoxyphenyl)acetate (2n), known compound.27 Colorless oil;
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20.2 mg, 43% yield; H NMR (400 MHz, CDCl3): δ 7.37 (dd, J = 7.8, 7.8 Hz, 1H),
7.27 (d, J = 6.0 Hz, 1H), 6.99 (dd, J = 7.6, 7.6 Hz, 1H), 6.95 (d, J = 7.8 Hz, 1H), 5.25
(s, 1H), 4.29-4.22 (m, 2H), 3.86 (s, 3H), 1.26 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (100
MHz, CDCl3) δ 169.5, 156.9, 130.6, 128.9, 122.8, 120.9, 111.1, 61.9, 60.2, 55.6, 14.0.
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Methyl 2-azido-2-(2-chlorophenyl)acetate (2o), unknown compound. Colorless oil;
20.0 mg, 44% yield; 1H NMR (400 MHz, CDCl3): δ 7.47-7.45 (m, 1H), 7.41-7.39 (m,
1H), 7.35-7.32 (m, 2H), 5.51 (s, 1H), 3.80 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3):
δ 169.1, 133.9, 132.1, 130.4, 130.1, 128.8, 127.4, 62.0, 53.1. IR (KBr): ѵ 3068, 3009,
2956, 2847, 2109, 1751, 1575, 1439 cm-1. HRMS (ESI) m/z: [M + Na]+ calcd. for
C9H8ClN3O2Na 248.0197, found: 248.0199.
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Ethyl 2-azido-2-(3,4-dichlorophenyl)acetate (2p), unknown compound. Colorless oil;
38.0 mg, 69% yield; H NMR (400 MHz, CDCl3): δ 7.51-7.47 (m, 2H), 7.25 (d, J =
1
8.4 Hz, 1H), 4.95 (s, 1H), 4.28-4.23 (m, 2H), 1.28 (t, J = 7.2 Hz, 3H); 13C{1H} NMR
(100 MHz, CDCl3): δ 168.2, 134.1, 133.5, 133.2, 130.9, 129.5, 126.7, 64.2, 62.6,
14.0. IR (KBr): ѵ 3094, 2986, 2934, 2112, 1745, 1594, 1472, 1201 cm-1. HRMS (ESI)
m/z: [M + Na]+ calcd. for C10H9Cl2N3O2Na 295.9964, found: 295.9964.
Ethyl 2-azido-2-(naphthalene-2-yl)acetate (2q), known compound,27 pale yellow oil;
30.0 mg 59% yield; 1H NMR (400 MHz, CDCl3): δ 7.90-7.86 (m, 4H), 7.54-7.48 (m,
3H), 5.13 (s, 1H), 4.32-4.20 (m, 2H), 1.26 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (100
MHz, CDCl3): δ 169.1, 133.5, 133.1, 131.4, 129.1, 128.3, 127.8, 127.2, 126.9, 126.7,
124.8, 65.6, 62.3, 14.1.
Ethyl 2-azido-2-(thiophen-3-yl)acetate (2r), unknown compound. Colorless oil; 23.0
mg, 55% yield; 1H NMR (400 MHz, CDCl3): δ 7.39-7.37 (m, 2H), 7.14-7.13 (m, 1H),
4.78 (s, 1H), 4.33-4.20 (m, 2H), 1.29 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 168.9, 133.9, 127.1, 126.4, 124.4, 62.2, 60.8, 14.0. IR (KBr): ѵ 3108, 2985,
2937, 2110, 1743, 1469, 1254, 1187 cm-1. HRMS (ESI) m/z: [M + Na]+ calcd. for
C8H9N3O2SNa 234.0308, found: 234.0310.
Ethyl 2-azido-2-(benzo[d][1,3]dioxol-5-yl)acetate (2s), unknown compound.
Colorless oil; 37.0 mg, 74% yield; 1H NMR (400 MHz, CDCl3): δ 6.88-6.80 (m, 3H),
5.99 (s, 2H), 4.86 (s, 1H), 4.31-4.16 (m, 2H), 1.34 (t, J = 7.2 Hz, 3H); 13C{1H} NMR
(100 MHz, CDCl3) δ 169.1, 148.4, 148.2, 127.6, 121.7, 108.5, 107.9, 101.5, 65.1,
62.1, 14.0. IR (KBr): ѵ 2985, 2905, 2782, 2109, 1851, 1743, 1610, 1494 cm-1. HRMS
(ESI) m/z: [M + Na]+ calcd. for C11H11N3O4Na 273.0642, found: 273.0643.
Isopropyl 2-azido-2-phenylacetate (2t), unknown compound. Colorless oil; 31.5 mg,
72% yield; 1H NMR (400 MHz, CDCl3): δ 7.40-7.39 (m, 5H), 5.15-5.08 (m, 1H), 4.90
(s, 1H), 1.28 (d, J = 6.4 Hz, 3H), 1.18 (d, J = 6.4 Hz, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 168.6, 134.1, 129.1, 129.0, 127.6, 70.0, 65.4, 21.7, 21.4. IR (KBr): ѵ 3067,
3035, 2985, 2938, 2108, 1740, 1603, 1456 cm-1. HRMS (ESI) m/z: [M + Na]+ calcd.
for C11H13N3O2Na+: 242.0900, found: 242.0902.
Benzyl 2-azido-2-phenylacetate (2u), known compound.28 Colorless oil; 37.2 mg, 70%
yield; 1H NMR (400 MHz, CDCl3): δ 7.38-7.36 (m, 5H), 7.32-7.31 (m, 3H), 7.26-7.24
(m, 2H), 5.24 (d, J = 12.0 Hz, 1H), 5.16 (dd, J = 12.0 Hz, 1H), 4.99 (s, 1H); 13C{1H}
NMR (100 MHz, CDCl3) δ 168.9, 134.9, 133.7, 129.3, 129.0, 128.5, 128.4, 128.2,
127.6, 67.6, 65.3.
Methyl 2-azido 2-(4-tert-butyl)phenyl)acetate (2v), unknown compound. Colorless
oil; 33.5 mg, 68% yield; 1H NMR (400 MHz, CDCl3): δ 7.43 (d, J = 8.4 Hz, 2H), 7.31
(d, J = 8.4 Hz, 2H), 4.94 (s, 1H), 3.78 (s, 3H), 1.32 (s, 9H); 13C{1H} NMR (100 MHz,
CDCl3) δ 169.8, 152.4, 130.8, 127.3, 126.1, 64.9, 52.9, 34.7, 31.2. IR (KBr): ѵ 3033,
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2962, 2908, 2871, 2107, 1917, 1749, 1612 cm-1. HRMS (ESI) m/z: [M + Na]+ calcd.
for C13H17N3O2Na+: 270.1213, found: 270.1216.
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Isopentyl 2-azido-2-phenylacetate (2w), unknown compound. Colorless oil; 37.0 mg,
75% yield; 1H NMR (400 MHz, CDCl3): δ 7.40-7.39 (m, 5H), 4.97 (s, 1H), 4.32-4.19
(m, 2H), 1.59-1.56 (m, 1H), 1.53-1.47 (m, 2H), 0.85 (t, J = 5.8 Hz, 6H); 13C{1H}
NMR (100 MHz, CDCl3) δ 169.2, 134.0, 129.2, 129.0, 127.6, 65.4, 64.8, 37.0, 24.9,
22.3. IR (KBr): ѵ 3067, 3035, 2961, 2931, 2873, 2107, 1744, 1603 cm-1. HRMS (ESI)
m/z: [M + Na]+ calcd. for C13H17N3O2Na 270.1213, found: 270.1216.
Allyl 2-azido-2-phenylacetate (2aa), unknown compound. Colorless oil; 30.0 mg,
70% yield; 1H NMR (400 MHz, CDCl3): δ 7.40 (s, 5H), 5.91-5.81 (m, 1H), 5.27-5.20
(m, 2H), 4.99 (s, 1H), 4.67 (s, 2H); 13C{1H} NMR (100 MHz, CDCl3): δ 168.8,
133.8, 131.1, 129.3, 129.1, 127.6, 119.1, 66.4, 65.3. IR (KBr): ѵ 3068, 3034, 2949,
2108, 1745, 1649, 1603, 1454 cm-1. HRMS (ESI) m/z: [M + Na]+ calcd. for
C11H11N3O2Na 240.0743, found: 240.0745.
Prop-2-yn-1-yl 2-azido-2-phenylacetate (2ab), unknown compound. Colorless oil;
36.5 mg, 85% yield; 1H NMR (400 MHz, CDCl3): δ 7.42-7.40 (m, 5H), 5.01 (s, 1H),
4.81 (dd, J = 15.6, 2.0 Hz, 1H), 4.72 (dd, J = 15.6, 2.4 Hz, 1H), 2.49 (s, 1H); 13C{1H}
NMR (100 MHz, CDCl3): δ 168.4, 133.3, 129.4, 129.1, 127.7, 76.5, 75.8, 65.0, 53.3.
IR (KBr): ѵ 3295, 3067, 3035, 2952, 2108, 1753, 1454, 1169 cm-1. HRMS (ESI) m/z:
[M + Na]+ calcd. for C11H9N3O2Na+: 238.0587; found: 238.0591.
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Prop-2-yn-1-yl
2-azido-2-(benzo[d][1,3]dioxol-5-yl)acetate
(2ac),
unknown
1
compound. Colorless oil; 36.3 mg, 70% yield; H NMR (400 MHz, CDCl3): δ
6.88-6.81 (m, 3H), 6.00 (s, 2H), 4.92 (s, 1H), 4.79 (dd, J = 15.2, 1.6 Hz, 1H), 4.71
(dd, J = 15.2, 1.6 Hz, 1H), 2.51 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 168.3,
148.6, 148.3, 126.8, 121.8, 108.6, 107.9, 101.5, 76.5, 75.8, 64.8, 53.3. IR (KBr): ѵ
3293, 2904, 2783, 2109, 1752, 1610, 1495, 1250 cm-1. HRMS (ESI) m/z: [M + Na]+
calcd. for C12H9N3O4Na 282.0485; found: 282.0491.
Ethyl 2-phenyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)acetate (3a), known compound.29
White solid, 40.0 mg, 65% yield; 1H NMR (400 MHz, CDCl3): δ 7.90 (s, 1H), 7.81 (d,
J = 7.2 Hz, 2H), 7.44-7.37 (m, 7H), 7.33-7.28 (m, 1H), 6.62 (s, 1H), 4.40-4.26 (m,
2H), 1.31 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 167.7, 147.8,
133.2, 130.4, 129.8, 129.5, 128.7, 128.2, 127.9, 125.7, 119.6, 66.1, 62.7, 14.0.
Ethyl 2-(4-bromophenyl)-2-(4-phenyl-1H-1,2,3-triazol-1-yl)acetate (3b), unknown
1
compound. Yellow solid, m.p. = 94 ℃~96 ℃, 38.4 mg, 50% yield; H NMR (400
MHz, CDCl3): δ 7.29 (s, 1H), 7.81 (d, J = 7.2 Hz, 2H), 7.43-7.30 (m, 7H), 6.59 (s,
1H), 4.40-4.26 (m, 2H), 1.31 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ
167.3, 148.0, 136.0, 131.7, 130.3, 129.7, 129.3, 128.8, 128.3, 125.7, 119.4, 65.4, 62.9,
14.0. IR (KBr): ѵ 3134, 3101, 3053, 3031, 2954, 1899, 1747, 1580 cm-1. HRMS (ESI)
m/z: [M + Na]+ calcd. for C18H16BrN3O2Na+: 408.0324; found: 408.0320.
Ethyl 2-(4-methylphenyl)-2-(4-phenyl-1H-1,2,3-triazol-1-yl)acetate (3c), unknown
1
compound. Yellow solid, m.p. = 96 ℃~ 98 ℃, 40.3 mg, 63% yield; H NMR (400
MHz, CDCl3): δ 7.86 (s, 1H), 7.80 (d, J = 7.2 Hz, 2H), 7.39 (dd, J = 8.0, 8.0 Hz, 2H),
7.33-7.30 (m, 3H), 7.26-7.23 (m, 2H), 6.58 (s, 1H), 4.39-4.25 (m, 2H), 2.38 (s, 3H),
13
1.30 (t, J = 7.2 Hz, 3H); C{1H} NMR (100 MHz, CDCl3) δ 167.8, 147.7, 139.9,
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130.5, 130.1, 128.7, 128.1, 127.9, 125.7, 119.6, 65.9, 62.6, 21.2, 14.0. IR (KBr): ѵ
3123, 2941, 1746, 1612, 1516, 1480, 1305, 1227 cm-1. HRMS (ESI) m/z: [M + H]+
calcd. for C19H20N3O2 322.1550; found: 322.1553.
Isopentyl
2-phenyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)acetate
(3d),
unknown
1
compound. White solid, m.p. = 106 ℃~108 ℃, 46.0 mg, 66% yield; H NMR (400
MHz, CDCl3): δ 7.90 (s, 1H), 7.81 (d, J = 7.6 Hz, 2H), 7.44-7.37 (m, 7H), 7.33-7.28
(m, 1H), 6.62 (s, 1H), 4.31-4.28 (m, 2H), 1.64-1.52 (m, 3H), 0.88 (d, J = 6.4 Hz, 6H);
13C{1H} NMR (100 MHz, CDCl3) δ 167.7, 147.8, 133.2, 130.4, 129.7, 129.4, 128.7,
128.1, 127.9, 125.7, 119.6, 66.1, 65.3, 36.9, 24.9, 22.3. IR (KBr): ѵ 3470, 3131, 3099,
3031, 2957, 1746, 1641, 1224 cm-1. HRMS (ESI) m/z: [M + H]+ calcd. for
C21H24N3O2 350.1864; found: 350.1866.
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Benzyl 2-phenyl -2-(4-phenyl-1H-1,2,3-triazol-1-yl)acetate (3e), unknown compound.
1
White solid, m.p. = 138 ℃ ~140 ℃ , 44.3 mg, 60% yield; H NMR (400 MHz,
CDCl3): δ 7.87 (s, 1H), 7.79 (d, J = 7.2 Hz, 2H), 7.40-7.29 (m, 13H), 6.67 (s, 1H),
13
5.28 (s, 2H); C{1H} NMR (100 MHz, CDCl3) δ 167.5, 147.8, 134.4, 132.9, 130.3,
129.7, 129.4, 128.7, 128.6, 128.4, 128.1, 127.9, 125.7, 119.6, 68.2, 66.0. IR (KBr): ѵ
3475, 3112, 3086, 3033, 2919, 1960, 1892, 1750 cm-1. HRMS (ESI) m/z: [M + H]+
+
calcd. for C23H20N3O2 : 370.1550; found: 370.1554.
Isopropyl
2-phenyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)acetate
(3f),
unknown
1
compound. White solid, m.p. = 112 ℃~115 ℃, 42.0 mg, 65% yield; H NMR (400
MHz, CDCl3): δ 7.90 (s, 1H), 7.81 (d, J = 7.6 Hz, 2H), 7.43-7.36 (m, 7H), 7.32-7.28
(m, 1H), 6.59 (s, 1H), 5.23-5.13 (m, 1H), 1.31 (d, J = 6.4 Hz, 3H), 1.25 (d, J = 6.4 Hz,
13
3H); C{1H} NMR (100 MHz, CDCl3) δ 167.1, 147.8, 133.3, 130.4, 129.6, 129.4,
128.7, 128.1, 127.8, 125.7, 119.6, 70.8, 66.1, 21.6, 21.4. IR (KBr): ѵ 3479, 3120,
2982, 2876, 1750, 1640, 1585, 1556 cm-1. HRMS (ESI) m/z: [M + H]+ calcd. for
C19H20N3O2 322.1550; found: 322.1552.
Ethyl 2-amino-2-phenylacetate (4a), known compound.30 Yellow oily liquid, 28.0 mg,
78% yield from 2a; 1H NMR (400 MHz, CDCl3): δ 7.39-7.27 (m, 5H), 4.59 (s, 1H),
13
4.24-4.08 (m, 2H), 1.95 (s, 2H), 1.21 (t, J = 7.2 Hz, 3H); C{1H} NMR (100 MHz,
CDCl3) δ 173.9, 140.4, 128.7, 127.9, 126.7, 61.3, 58.8, 14.0.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications
website at DOI: 10.1021/acs.joc.xxxxxx.
Control Experiments, 1H and 13C NMR {1H} spectra of products (PDF)
AUTHOR INFORMATION
Corresponding Author
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*E-mail: xytang@hust.edu.cn
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ORCID
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Xiang-Ying Tang: 0000-0003-3959-3715
Notes
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The authors declare no competing financial interest.
ACKNOWLEDGMENT
We are grateful for the financial support provided by the National Natural Science
Foundation of China (21871100), the Fundamental Research Funds for the Central
Universities (2017KFYXJJ166), Huazhong University of Science and Technology
(HUST), and the Opening Fund of Hubei Key Laboratory of Bioinorganic Chemistry
and Materia Medica (No. BCMM201805). We also thank the Analytical and Testing
Center of HUST, Analytical and Testing Center of the School of Chemistry and
Chemical Engineering (HUST) for access to their facilities.
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