Copper-Catalyzed Nitrogenation of Aromatic and Aliphatic Aldehydes: A Direct Route to Carbamoyl Azides

Article abstract of DOI:10.1055/s-0039-1690683

An efficient copper-catalyzed synthesis of carbamoyl azides directly from aldehydes has been developed. Both aromatic aldehydes and aliphatic aldehydes, together with other commercially available reactants, can be used as substrates in this radical relay reaction. Broad substrate scope, simple operation, readily available reagents, and good functionality tolerance make this method very attractive.

Full text of DOI:10.1055/s-0039-1690683

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2019, 51, A–E
paper
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en
R. Wei et al.
Paper
Synthesis
Copper-Catalyzed Nitrogenation of Aromatic and Aliphatic
Aldehydes: A Direct Route to Carbamoyl Azides
Rongbiao Weia,b
Liang Geb
O
R
O
[Cu]/TBPB
+
TMSN3
N
N3
R
H
H
Hongli Baob
Saihu Liao*a
Yajun Li*b
0
0
0
0-0
0
0
3-1
0
3
0-
5
0
8
9
Aliphatic aldehydes and aryl aldehydes
TBPB as the oxidant and initiator
Yield up to 93%
Copper catalysis
a College of Chemistry, Fuzhou University, 2 Xueyuan Road, Fuzhou, Fujian 350108, P. R. of China
shliao@fzu.edu.cn
b State Key Laboratory of Structural Chemistry, Key Laboratory of Coal to Ethylene Glycol and Its
Related Technology, Center for Excellence in Molecular Synthesis, Fujian Institute of Research on
the Structure of Matter, University of Chinese Academy of Sciences, 155 Yangqiao Road West,
Fuzhou, Fujian 350002, P. R. of China
liyajun@fjirsm.ac.cn
Received: 24.07.2019
a) Synthesis of carbamoyl azides with high-valent Iodine reagents
Accepted after revision: 01.09.2019
Published online: 23.09.2019
DOI: 10.1055/s-0039-1690683; Art ID: ss-2019-h0416-op
+ or I3+
O
O
I
azido
sources
+
R
N
N3
R
H
H
b) Jiao's work with KI/TBHP system
Abstract An efficient copper-catalyzed synthesis of carbamoyl azides
directly from aldehydes has been developed. Both aromatic aldehydes
and aliphatic aldehydes, together with other commercially available re-
actants, can be used as substrates in this radical relay reaction. Broad
substrate scope, simple operation, readily available reagents, and good
functionality tolerance make this method very attractive.
O
O
KI/TBHP
+
TMSN3
Ar
N
N3
Ar
H
H
c) Our work: Copper-catalyzed synthesis of carbamoyl azides
O
O
[Cu]/TBPB
+
TMSN3
R
N
N3
R
H
Key words copper catalyst, carbamoyl azides, aromatic aldehydes,
H
aliphatic aldehydes, nitrogenation, radical
Aliphatic aldehydes and aryl aldehydes
TBPB as the oxidant and initiator
Yield up to 93%
Copper catalysis
Carbamoyl azides are valuable intermediates and build-
ing blocks in organic synthesis,1 because they can be easily
converted into amines,2 amides,3 ureas,4 urethanes,5 or
tetrazoles.6 Generally, carbamoyl azides are prepared by the
reaction of carboxylic acid or acid derivatives with trimeth-
ylsilyl azide or sodium azide, forming acyl azides. This is
followed by a Curtius rearrangement7 and subsequent addi-
tion of hydrazoic acid.8 Alternatively, taking advantages of
the versatile functionality transformations, aldehydes can
be used for the preparation of carbamoyl azides9 but the
documented methods for the synthesis of carbamoyl azides
from aldehydes often employed unstable or air sensitive
iodine(I) or iodine(III) reagents (Scheme 1). Consequently,
practical approaches for the convenient transformation of
aldehydes to carbamoyl azides are still highly sought-after.
Recently, progress towards transformation of aldehydes
to carbamoyl azides with the help of the potassium
iodide/tert-butyl hydroperoxide (TBHP) system was report-
ed10 (Scheme 1). Although improvements have been made,
this reaction does not work with aliphatic aldehydes. In
2019, we disclosed an iron-catalyzed radical acyl-azidation
of alkenes at ambient temperature.11 This allows both aro-
matic aldehydes and aliphatic aldehydes to be used as the
Scheme 1 The synthesis of carbamoyl azides from aldehydes
acyl radical precursors, with trimethylsilyl azide (TMSN3)
as the azido source and TBHP as the initiator. During the op-
timization of the reaction conditions, a small amount of a
carbamoyl azide was isolated. This unexpected result in-
spired us to develop a practical and efficient method for the
direct synthesis of carbamoyl azides with both aromatic al-
dehydes and aliphatic aldehydes to meet the demand for
variety in the synthesis of carbamoyl azides. We report here
the novel copper-catalyzed synthesis of carbamoyl azides
directly from aromatic aldehydes and aliphatic aldehydes
(Scheme 1).
To test the hypothesis concerning the synthesis of car-
bamoyl azides, we initiated the reaction of benzaldehyde
(1a) with TMSN3 in acetonitrile using TBHP as the radical
initiator. Parallel with our recently reported alkene acyl-
azidations,11 iron salts were examined first. Under the given
reaction conditions, ferric trifluoromethanesulfonate [ferric
triflate, Fe(OTf)3], which is effective in the acyl-azidation
reaction, afforded the desired carbamoyl azide 3a in only
14% yield (Table 1, entry 1). Other iron salts, such as
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B
R. Wei et al.
Paper
Synthesis
Fe(OTf)2, Fe(acac)2, FeC2O4·2H2O, FeSO4·7H2O, FeCl2,
Fe(OAc)2, FeCl3, Fe(acac)3, and FeBr3 general produced the
corresponding product 3a in 6–36% yield (entry 2). Other
metals, such as Ni(acac)2, PdCl2, AlCl3, and RuCl3 also failed
to provide satisfactory results (entries 3–6). It was encour-
aging to observe that copper(II) oxalate catalyst delivered
3a in 61% yield (entry 7), although other copper salts [CuCl,
CuBr, CuI, Cu(OAc), CuTc, Cu(MeCN)4PF6, Cu(OTf)2, CuCl2,
CuBr2, CuF2, Cu(OAc)2, and Cu(acac)2] failed to improve the
yield of 3a (entries 8 and 9). The effect of changing the sol-
vent from acetonitrile to dichloroethane, 1,4-dioxane, n-
hexane, or toluene was not obvious (entries 10–13), and
solvents such as DME, DMF, DMSO, and THF completely
blocked the formation of 3a (entry 14). TBPB (tert-butyl
peroxybenzoate) is an excellent radical initiator12 and when
it was used in place of TBHP, the isolated yield of 3a was
dramatically improved to 86%. In the absence of a metal cat-
alyst however, only 17% yield of 3a was obtained.
lyzed nitrogenation of aldehydes. As shown in Scheme 2, a
range of aryl aldehydes afforded the corresponding carbam-
oyl azides 3a–l in moderate to excellent yields. Functional
groups, such as electron-donating methyl group, tert-butyl
group, and methoxy group, and mild electron-withdrawing
groups, such as Cl and Br, were all tolerated under the opti-
mized reaction conditions. The halogen substituents can al-
low further useful transformations. In particular, 3,4,5-tri-
methoxybenzaldehyde successfully produced the corre-
sponding product 3l in 80% yield. This method can also
work with various aliphatic aldehydes 3m–r. Carbamoyl
azides with either primary or secondary alkyl groups can
be obtained directly under the standard reaction condi-
tions. The compatibility of C=C bond (→ 3q) and free hy-
droxyl group (→ 3r) demonstrates the excellent functional
group tolerance. Notably, pivaldehyde, as an example of ter-
tiary aldehyde, failed to provide the desired product. It
Under the optimal reaction conditions, we studied the
scope for the synthesis of carbamoyl azides directly from
aldehydes. It was found that both aromatic aldehydes and
aliphatic aldehydes can be used in this feasible copper-cata-
(CuC2O4)2*H2O (2.5 mol%)
O
TBPB (1.5–2 equiv)
R
TMSN3
+
R
N
N3
O
H
MeCN (2 mL), 70–80 °C, 16 h
1
2
3
Table 1 Optimization of Reaction Conditionsa
Aromatic aldehydes
tBu
N3
MeO
O
O
O
O
O
O
cat. (5 mol%)
TBHP (1.5 equiv)
O
O
N
H
N3
N
N
H
N3
TMSN3
N
N3
+
H
H
N
H
N3
solvent, 70 °C, N2
3a
3b
72%
3c
81%
3d
1a
2
3a
86%
61%
Ph
Cl
Br
Entry Catalyst
Solvent
Yield (%)b
O
O
N
N3
N
N3
N
N3
N
N3
H
1
2
Fe(OTf)3
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
14
H
H
H
3e
93%
3f
74%
3g
3h
other iron salts
Ni(acac)2
PdCl2
6–36
15
86%
81%
3
OMe
O
O
O
MeO
MeO
4
13
O
MeO
N
N3 Br
N
N3
N
H
N3
5
AlCl3
9
H
H
N
N3
H
6
RuCl3
20
3i
65%
3j
88%
3k
58%
3l
80%
7
(CuC2O4)2·H2O (2.5 mol%)
Cu(I) salts
MeCN
61 (47)c
31–47
26–54
26
Aliphatic aldehydes
8
MeCN
O
O
O
O
9
other Cu(II) salts
MeCN
N
H
N3
N
H
N3
N
H
N3
10
11
12
13
14
15d
16d
(CuC2O4)2·H2O (2.5 mol%)
(CuC2O4)2·H2O (2.5 mol%)
(CuC2O4)2·H2O (2.5 mol%)
(CuC2O4)2·H2O (2.5 mol%)
(CuC2O4)2·H2O (2.5 mol%)
(CuC2O4)2·H2O (2.5 mol%)
–
DCE
3m
3n
3o
66%
1,4-dioxane
n-hexane
toluene
13
58%
76%
7
O
10
OH
O
N
N3
N
H
N3
7
DME/DMF/DMSO/THF
trace
94 (86)c
17
H
N
H
N3
MeCN
MeCN
3p
3q
3r
67%
44%
55%
a Reaction conditions: 1a (0.5 mmol), 2 (3 equiv), TBHP (in decane, 1.5
equiv), catalyst (5 mol%, unless otherwise stated) in solvent (2 mL) at 70 °C.
b Yields were determined by 1H NMR analysis.
Scheme 2 Substrate scope. Reagents and conditions: for 3a, 3c, 3o–q:
aldehyde (0.5 mmol), TMSN3 (3 equiv), TBPB (1.5 equiv), (CuC2O4)2·H2O
(2.5 mol%), MeCN (2 mL), 70 °C for 16 h; for others: aldehyde (0.5
mmol), TMSN3 (4 equiv), TBPB (2 equiv), (CuC2O4)2·H2O (2.5 mol%),
MeCN (2 mL), 80 °C for 16 h.
c Yield of isolated product in parentheses.
d TBPB (1.5 equiv) was used instead of TBHP.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–E

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R. Wei et al.
Paper
Synthesis
(CuC2O4)2•H2O
Curtius
rearrangement
O
O
O
O
Cu(I)X
R
C
O
Ph
R
N3
N
A
TBPB
F
TMSN3
H+
H
R
O
1
O
N3
3
O
R
N
R
O
H
C
D
N3
OOCPh
OH
Cu(II)X
Cu(II)X
E
B
TMSOOCPh
TMSN3
Scheme 3 Plausible mechanism
should be mentioned that the relatively lower yields for 3k,
3m, 3p, and 3q might be attributed to the undetectable side
reactions.
od features broad substrate scope, simple operation, readily
available reagents, and good functional group tolerance,
and is very attractive.
Preliminary mechanistic studies were then carried out
to understand the reaction mechanism. With the addition
of 1.5 equivalents of TEMPO (2,2,6,6-tetramethylpiperi-
dine-1-oxyl), a radical scavenger, under the standard reac-
tion conditions, the yield of the corresponding product 3a
fell sharply to 30%. Moreover, a BHT-Bz adduct was detected
when the reaction with 1a was performed in the presence
of 1.5 equivalents of BHT (butylated hydroxytoluene). The
mechanistic experiments above suggested that a radical
process was involved in the mechanistic cycle. Based on the
outcomes of this method and our recently published re-
sults,11–13 a plausible mechanism for the copper-catalyzed,
direct synthesis of carbamoyl azides from both aromatic al-
dehydes and aliphatic aldehydes is proposed as shown in
Scheme 3. This mechanistic cycle starts with the active
Cu(I)X species A. Initially, a single-electron transfer (SET)
Unless otherwise indicated, reactions were carried out under an at-
mosphere of N2 in flame-dried glassware with magnetic stirring.
Commercially obtained reagents were used directly as received. Sol-
vents were dried by an Innovative Technology Solvent Purification
System. Liquids and solutions were transferred by syringe. All reac-
tions were monitored by TLC. 1H and 13C NMR spectra were recorded
on a Bruker-BioSpin Avance III HD spectrometer. Data for 1H NMR
spectra are reported relative to CHCl3 as an internal standard (7.26
ppm) and are reported as follows: chemical shift (ppm), multiplicity,
coupling constant (Hz), and integrated values. Data for 13C NMR spec-
tra are reported relative to CHCl3 as an internal standard (77.23 ppm)
and are cited in terms of chemical shift (ppm). HRMS data were re-
corded on Waters Micromass GCT Premier or Thermo Fisher Scientific
LTQ FT Ultra.
Copper-Catalyzed Azidation of Aldehydes; Phenylcarbamoyl Azide
(3a); Typical Procedure (Table 1 and Scheme 2)
process between complex
A and TBPB generates a
Cu(II)X(OOCPh) species B and a tert-butyloxyl radical C,
which can abstract an H-atom from the aldehyde to afford
the acyl radical D.14 Meanwhile, upon ligand exchange with
TMSN3, the Cu(II) species B is converted into an azido Cu(II)
species E. The species E then reacts with the acyl radical D
to afford the acyl azide intermediate F and regenerates the
active copper species A. The acyl azide undergoes a Curtius
rearrangement,7 and this is followed by the interception of
TMSN3, to produce the carbamoyl azide product.
In conclusion, an efficient copper-catalyzed synthesis of
carbamoyl azides directly from aldehydes has been devel-
oped. A range of aldehydes, including aromatic aldehydes
and aliphatic aldehydes, can be used for this radical relay
process under the standard reaction conditions. This meth-
Benzaldehyde (1a; 53 mg, 0.5 mmol, 1 equiv), TMSN3 (2; 173 mg, 1.5
mmol, 3 equiv), MeCN (2 mL), TBPB (145 mg, 0.75 mmol, 1.5 equiv),
and (CuC2O4)2·H2O (4 mg, 2.5 mol%) were placed in a Schlenk tube
with a stirring bar under a N2 atmosphere. The reaction mixture was
heated at 70 °C for 16 h, and then cooled to r.t. The reaction was
quenched with EtOAc, and then washed with H2O (3 × 15 mL). The
combined organic phases were dried (MgSO4). The solvent was re-
moved by evaporation under vacuum and the residue was chromato-
graphed on silica gel (PE/EtOAc 20:1 → 5:1) to yield 3a2b as a white
solid; yield: 69.8 mg (86%); mp 106–107 °C (Lit.15 mp 106–107 °C).
1H NMR (600 MHz, CDCl3):  = 7.46 (d, J = 7.9 Hz, 2 H), 7.38 (br, 1 H),
7.32 (t, J = 7.9 Hz, 2 H), 7.13 (t, J = 7.3 Hz, 1 H).
13C NMR (150 MHz, CDCl3):  = 154.37, 137.06, 129.18, 124.76,
119.58.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–E

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R. Wei et al.
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Synthesis
p-Tolylcarbamoyl Azide (3b)2b
13C NMR (100 MHz, CDCl3):  = 160.36, 154.22, 138.26, 130.04,
White solid; yield: 63.4 mg (72%); mp 131–132 °C (Lit.9a mp 131–133
111.62, 110.48, 105.25, 55.48.
°C).
(m-Bromophenyl)carbamoyl Azide (3j)17
1H NMR (600 MHz, CDCl3):  = 7.32 (d, J = 8.1 Hz, 2 H), 7.12 (d, J = 8.2
White solid; yield: 105.6 mg (88%); mp 95–96 °C.
Hz, 2 H), 7.06 (s, 1 H), 2.32 (s, 3 H).
1H NMR (400 MHz, CDCl3):  = 7.69 (s, 1 H), 7.33 (d, J = 8.1 Hz, 1 H),
7.25 (d, J = 7.6 Hz, 1 H), 7.18 (t, J = 8.0 Hz, 1 H), 7.09 (s, 1 H).
13C NMR (150 MHz, CDCl3):  = 154.20, 134.53, 134.50, 129.78,
119.66, 21.00.
13C NMR (100 MHz, CDCl3):  = 154.33, 138.32, 130.62, 127.85,
122.99, 122.40, 117.92.
[p-(tert-Butyl)phenyl]carbamoyl Azide (3c)2b
White solid; yield: 88.3 mg (81%); mp 144–146 °C.
1H NMR (400 MHz, CDCl3):  = 7.39–7.31 (m, 4 H), 7.06 (s, 1 H), 1.29
(s, 9 H).
o-Tolylcarbamoyl Azide (3k)2b
White solid; yield: 51.1 mg (58%); mp 98–99 °C (Lit.15 mp 97–99 °C).
1H NMR (400 MHz, CDCl3):  = 7.78 (d, J = 7.9 Hz, 1 H), 7.25–7.16 (m, 2
H), 7.10 (t, J = 7.2 Hz, 1 H), 6.77 (s, 1 H), 2.25 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 154.23, 147.86, 134.44, 126.15,
119.33, 34.56, 31.48.
13C NMR (100 MHz, CDCl3):  = 154.48, 134.91, 130.73, 128.74,
127.08, 125.55, 122.18, 17.73.
(p-Methoxyphenyl)carbamoyl Azide (3d)2b
White solid; yield: 58.6 mg (61%); mp 114–116 °C.
(3,4,5-Trimethoxyphenyl)carbamoyl Azide (3l)
1H NMR (600 MHz, CDCl3):  = 7.34 (d, J = 8.9 Hz, 2 H), 6.93 (s, 1 H),
6.86 (d, J = 9.0 Hz, 2 H), 3.79 (s, 3H).
White solid; yield: 100.9 mg (80%); mp 114–116 °C.
1H NMR (600 MHz, CDCl3):  = 7.37 (s, 1 H), 6.72 (s, 2 H), 3.79 (s, 3 H),
13C NMR (150 MHz, CDCl3):  = 156.88, 154.27, 130.10, 121.44,
3.75 (s, 6 H).
114.51, 55.68.
13C NMR (150 MHz, CDCl3):  = 154.21, 153.62, 134.98, 133.25, 97.11,
61.19, 56.27.
[1,1′-Biphenyl]-4-ylcarbamoyl Azide (3e)2b
HRMS (ESI): m/z [M + Na+] calcd for [C10H12N4O4Na]+: 275.0751;
White solid; yield: 110.7 mg (93%); mp 149–150 °C.
1H NMR (400 MHz, DMSO-d6):  = 10.43 (s, 1 H), 7.72–7.62 (m, 6 H),
7.47 (t, J = 7.7 Hz, 2 H), 7.36 (t, J = 7.3 Hz, 1 H).
13C NMR (100 MHz, DMSO-d6):  = 154.59, 140.48, 138.59, 136.41,
found: 275.0752.
Phenethylcarbamoyl Azide (3m)9c
White solid; yield: 55.2 mg (58%); mp 83–85 °C (Lit.15 mp 85–87 °C).
129.86, 128.10, 128.07, 127.27, 120.32.
1H NMR (600 MHz, CDCl3):  = 7.34–7.30 (m, 2 H), 7.25 (t, J = 7.4 Hz,
1 H), 7.19 (d, J = 6.9 Hz, 2 H), 5.22 (s, 1 H), 3.53–3.47 (m, 2 H), 2.83 (t,
J = 7.0 Hz, 2 H).
13C NMR (150 MHz, CDCl3):  = 156.58, 138.35, 128.90, 128.88,
126.88, 42.35, 35.79.
(p-Chlorophenyl)carbamoyl Azide (3f)2b
White solid; yield: 72.5 mg (74%); mp 104–105 °C (Lit.16 mp 103–104 °C).
1H NMR (600 MHz, CDCl3):  = 7.39 (d, J = 8.6 Hz, 2 H), 7.31–7.28 (m,
2 H), 6.92 (s, 1 H).
13C NMR (150 MHz, CDCl3):  = 154.41, 135.67, 129.92, 129.35,
120.76.
sec-Butylcarbamoyl Azide (3n)
Colorless oil; yield: 54 mg (76%).
(p-Bromophenyl)carbamoyl Azide (3g)2b
White solid; yield: 103.6 mg (86%); mp 78–80 °C (Lit.3a mp 77–78 °C).
1H NMR (400 MHz, CDCl3):  = 7.44 (d, J = 8.8 Hz, 2 H), 7.33 (d, J = 8.6
Hz, 2 H), 6.92 (s, 1 H).
13C NMR (100 MHz, CDCl3):  = 154.18, 136.16, 132.38, 120.93,
117.52.
1H NMR (600 MHz, CDCl3):  = 4.97 (s, 1 H), 3.72 (dq, J = 8.6, 6.6 Hz,
1 H), 1.47 (pd, J = 7.5, 1.2 Hz, 2 H), 1.14 (d, J = 6.6 Hz, 3 H), 0.90 (t, J =
7.5 Hz, 3 H).
13C NMR (150 MHz, CDCl3):  = 155.94, 48.96, 29.72, 20.51, 10.39.
HRMS (ESI): m/z [M + Na+] calcd for [C5H10N4ONa]+: 165.0747; found:
165.0743.
Cyclohexylcarbamoyl Azide (3o)9c
White solid; yield: 55.5 mg (66%); mp 105–106 °C (Lit.15 mp 105–106
m-Tolylcarbamoyl Azide (3h)16
White solid; yield: 71.4 mg (81%); mp 104–106 °C.
1H NMR (600 MHz, CDCl3):  = 7.28 (s, 1 H), 7.25–7.18 (m, 2 H), 7.06
(s, 1 H), 6.95 (d, J = 7.0 Hz, 1 H), 2.33 (s, 3 H).
13C NMR (150 MHz, CDCl3):  = 154.21, 139.34, 136.98, 129.15,
125.63, 120.10, 116.59, 21.59.
°C).
1H NMR (600 MHz, CDCl3):  = 5.15 (s, 1 H), 3.60–3.53 (m, 1 H), 1.94–
1.88 (m, 2 H), 1.73–1.65 (m, 2 H), 1.62–1.55 (m, 1 H), 1.37–1.28 (m,
2 H), 1.18–1.09 (m, 2 H).
13C NMR (150 MHz, CDCl3):  = 155.61, 50.27, 33.07, 25.48, 24.83.
(m-Methoxyphenyl)carbamoyl Azide (3i)16
White solid; yield: 62.4 mg (65%); mp 96–97 °C (Lit.17 mp 96–97 °C).
1H NMR (400 MHz, CDCl3):  = 7.25–7.16 (m, 2 H), 7.14 (s, 1 H), 6.92
(d, J = 7.8 Hz, 1 H), 6.67 (d, J = 9.9 Hz, 1 H), 3.78 (s, 3 H).
[1-(4-Isopropylphenyl)propan-2-yl]carbamoyl Azide (3p)
Colorless oil; yield: 54.1 mg (44%).
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–E

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R. Wei et al.
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Synthesis
1H NMR (400 MHz, CDCl3):  = 7.14 (d, J = 8.0 Hz, 2 H), 7.05 (d, J = 8.1
Hz, 2 H), 4.93 (s, 1 H), 4.11–3.98 (m, 1 H), 2.86 (pent, J = 6.9 Hz, 1 H),
2.78 (dd, J = 13.6, 5.8 Hz, 1 H), 2.67 (dd, J = 13.6, 7.0 Hz, 1 H), 1.21 (d,
J = 6.9 Hz, 6 H), 1.12 (d, J = 6.7 Hz, 3 H).
13C NMR (100 MHz, CDCl3):  = 155.79, 147.45, 134.67, 129.54,
126.75, 48.37, 42.08, 33.91, 29.90, 24.20, 20.11.
(2) (a) Sans, M.; Illa, O.; Ortuno, R. M. Org. Lett. 2012, 14, 2431.
(b) Feng, P.; Sun, X.; Su, Y.; Li, X.; Zhang, L.-H.; Shi, X.; Jiao, N.
Org. Lett. 2014, 16, 3388.
(3) (a) Brandt, J. C.; Wirth, T. Beilstein J. Org. Chem. 2009, 5, 30.
(b) Verardo, G.; Gorassini, A. Eur. J. Org. Chem. 2013, 5387.
(4) (a) Uneyama, K.; Makio, S.; Nanbu, H. J. Org. Chem. 1989, 54,
872. (b) Li, X.-Q.; Wang, W.-K.; Han, Y.-X.; Zhang, C. Adv. Synth.
Catal. 2010, 352, 2588.
HRMS (ESI): m/z [M + Na+] calcd for [C13H18N4ONa]+: 269.1373; found:
269.1372.
(5) (a) Paz, J.; Perez-Balado, C.; Iglesias, B.; Munoz, L. J. Org. Chem.
2010, 75, 3037. (b) Lv, Z.; Li, Z.; Liang, G. Org. Lett. 2014, 16,
1653.
Dec-9-en-1-ylcarbamoyl Azide (3q)
Colorless oil; yield: 61.6 mg (55%).
(6) (a) Tsuge, O.; Urano, S.; Oe, K. J. Org. Chem. 1980, 45, 5130.
(b) He, P.; Wu, L.; Wu, J. T.; Yin, X.; Gozin, M.; Zhang, J.-G. Dalton
Trans. 2017, 46, 8422.
(7) (a) Curtius, T. J. Prakt. Chem. 1894, 50, 275. (b) Curtius, T. Ber.
Dtsch. Chem. Ges. 1890, 23, 3023.
1H NMR (400 MHz, CDCl3):  = 5.80 (ddt, J = 16.9, 10.2, 6.7 Hz, 1 H),
5.12 (s, 1 H), 5.02–4.95 (m, 1 H), 4.94–4.90 (m, 1 H), 3.26–3.17 (m, 2
H), 2.07–1.98 (m, 2 H), 1.55–1.45 (m, 2 H), 1.41–1.33 (m, 2 H), 1.31–
1.25 (m, 8 H).
(8) (a) Prakash, G. K. S.; Iyer, P. S.; Arvanaghi, M.; Olah, G. A. J. Org.
Chem. 1983, 48, 3358. (b) Dunn, P. J.; Haener, R.; Rapoport, H.
J. Org. Chem. 1990, 55, 5017. (c) Yamaguchi, S.; Uchiuzoh, Y.;
Sanada, K. J. Heterocycl. Chem. 1995, 32, 419. (d) Froeyen, P.
Synth. Commun. 1996, 26, 4549. (e) Huang, Y.; Zhang, Y.-B.;
Chen, Z.-C.; Xu, P.-F. Tetrahedron: Asymmetry 2006, 17, 3152.
(f) Katritzky, A. R.; Widyan, K.; Kirichenko, K. J. Org. Chem. 2007,
72, 5802. (g) Kangani, C. O.; Day, B. W.; Kelley, D. E. Tetrahedron
Lett. 2008, 49, 914. (h) Verardo, G.; Bombardella, E.; Geatti, P.;
Strazzolini, P. Synthesis 2008, 438. (i) Salama, T. A.; Elmorsy, S.
S.; Khalil, A.-G. M.; Ismail, M. A. Chem. Lett. 2011, 40, 1149.
(j) Zhang, D.; Zheng, H.; Wang, X. Tetrahedron 2016, 72, 1941.
(9) (a) Li, X.-Q.; Zhao, X.-F.; Zhang, C. Synthesis 2008, 2589.
(b) Marinescu, L.; Thinggaard, J.; Thomsen, I. B.; Bols, M. J. Org.
Chem. 2003, 68, 9453. (c) Marinescu, L. G.; Pedersen, C. M.; Bols,
M. Tetrahedron 2005, 61, 123. (d) Pedersen, C. M.; Marinescu, L.
G.; Bols, M. Org. Biomol. Chem. 2005, 3, 816.
13C NMR (100 MHz, CDCl3):  = 156.53, 139.31, 114.37, 41.33, 33.95,
29.73 29.51, 29.33, 29.19, 29.05, 26.85.
HRMS (ESI): m/z [M + Na+] calcd for [C11H20N4ONa]+: 247.1529; found:
247.1531.
(6-Hydroxy-2,6-dimethylheptyl)carbamoyl Azide (3r)
Colorless oil; yield: 76.5 mg (67%).
1H NMR (600 MHz, CDCl3):  = 5.39 (s, 1 H), 3.18–2.99 (m, 2 H), 1.64
(dq, J = 13.2, 6.8 Hz, 1 H), 1.46–1.37 (m, 3 H), 1.35–1.27 (m, 2 H), 1.20–
1.18 (m, 6 H), 1.15–1.07 (m, 1 H), 0.88 (d, J = 6.7 Hz, 3 H).
13C NMR (150 MHz, CDCl3):  = 156.74, 71.11, 47.11, 43.99, 34.69,
33.50, 29.50, 29.34, 21.63, 17.62.
HRMS (ESI): m/z [M + Na+] calcd for [C10H20N4ONa]+: 251.1478; found:
251.1479.
(10) Song, S.; Feng, P.; Zou, M.; Jiao, N. Chin. J. Chem. 2017, 35, 845.
(11) Ge, L.; Li, Y.; Bao, H. Org. Lett. 2019, 21, 256.
(12) (a) Xiong, H.; Li, Y.; Qian, B.; Wei, R.; Van der Eycken, E. V.; Bao,
H. Org. Lett. 2019, 21, 776. (b) Xiong, H.; Ramkumar, N.; Chiou,
M.-F.; Jian, W.; Li, Y.; Su, J.-H.; Zhang, X.; Bao, H. Nat. Commun.
2019, 10, 122.
(13) Jiao, Y.; Chiou, M.-F.; Li, Y.; Bao, H. ACS Catal. 2019, 9, 5191.
(14) (a) Leifert, D.; Daniliuc, C. G.; Studer, A. Org. Lett. 2013, 15, 6286.
(b) Li, J.; Wang, D. Z. Org. Lett. 2015, 17, 5260. (c) Lv, L.; Lu, S.;
Guo, Q.; Shen, B.; Li, Z. J. Org. Chem. 2015, 80, 698. (d) Matcha,
K.; Antonchick, A. P. Angew. Chem. Int. Ed. 2013, 52, 2082.
(e) Wang, J.; Liu, C.; Yuan, J.; Lei, A. Angew. Chem. Int. Ed. 2013,
52, 2256. (f) Zhao, J.; Li, P.; Xia, C.; Li, F. Chem. Commun. 2014,
50, 4751.
Funding Information
We thank the National Key R & D Program of China (Grant No.
2017YFA0700103), the NSFC (Grant Nos. 21602028, 21672213,
21871258), the Strategic Priority Research Program of the Chinese
Academy of Sciences (Grant No. XDB20000000), and the Haixi Insti-
tute of CAS (Grant No. CXZX-2017-P01) for financial support.
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Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0039-1690683.
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(15) Li, X.-Q.; Wang, W.-K.; Zhang, C. Adv. Synth. Catal. 2009, 351,
2342.
(16) Yadav, L.; Yadav, V.; Srivastava, V. Synlett 2016, 27, 2826.
(17) Reddy, P. S.; Yadagiri, P.; Lumin, S.; Shin, D.-S.; Falck, J. R. Synth.
Commun. 1988, 18, 545.
References
(1) (a) Lieber, E.; Minnis, R. L.; Rao, C. N. R. Chem. Rev. 1965, 65, 377.
(b) Scriven, E. F. V.; Turnbull, K. Chem. Rev. 1988, 88, 297.
(c) Bräse, S.; Gil, C.; Knepper, K.; Zimmermann, V. Angew. Chem.
Int. Ed. 2005, 44, 5188.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–E