Electrochemical regioselective azidoiodination of alkenes

Article abstract of DOI:10.1016/j.tet.2016.12.058

An efficient electrochemical approach to the vicinal iodoazides has been developed through constant current electrolysis of alkenes with NaN₃and NaI in methanol. The reaction is proposed to proceed via a cyclic iodonium intermediate and thereby gives Markovnikov addition products exclusively.

Full text of DOI:10.1016/j.tet.2016.12.058

Accepted Manuscript
Electrochemical regioselective azidoiodination of alkenes
Wei-qing Yan, Meng-ying Lin, R. Daniel Little, Cheng-Chu Zeng
PII:
S0040-4020(16)31355-2
10.1016/j.tet.2016.12.058
TET 28350
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 24 October 2016
Revised Date: 20 December 2016
Accepted Date: 23 December 2016
Please cite this article as: Yan W-q, Lin M-y, Little RD, Zeng C-C, Electrochemical regioselective
azidoiodination of alkenes, Tetrahedron (2017), doi: 10.1016/j.tet.2016.12.058.
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ACCEPTED MANUSCRIPT
Electrochemical regioselective azidoiodination of alkenes
Wei-qing Yan,a Meng-ying Lin,a R. Daniel Little b and Cheng-Chu Zeng,a*
a College of Life Science & Bioengineering, Beijing University of Technology, Beijing
100124, China. Corresponding author: zengcc@bjut.edu.cn
b
Department of Chemistry & Biochemistry, University of California, Santa Barbara,
Santa Barbara, California 93106-9510, USA
Graphical Abstract:
I
NaN3 (2.0 equiv), NaI (2.0 equiv)
N3
R1
R1
R3
R3
LiClO4 (0.1 M) / MeOH
divided cell, r.t., CCE
R2
R2
2
1
13 examples, up to 65% yield
Abstract
An efficient electrochemical approach to the vicinal iodoazides has been
developed through constant current electrolysis of alkenes with NaN3 and NaI in
methanol. The reaction is proposed to proceed via a cyclic iodonium intermediate and
thereby gives Markovnikov addition products exclusively.
Key words: azidoiodination of alkenes; Electrosynthesis; Markovnikov addition;
cyclic iodonium intermediate
Introduction
Difunctionalization of alkenes constitutes one of the most important chemical
transformations in organic chemistry.1-3 Among them, azidoiodination of alkenes has
attracted considerable attention since the resulting vicinal iodoazides contain
extraordinarily useful iodo and azido functional groups, which can readily be
transformed into versatile intermediates such as vinyl azides, amines, aziridine and
tetrazoles.4-7 In addition, along with the development of “click chemistry”, various
organic azides are required as starting materials for producing 1,2,3-triazoles
possessing a wide spectrum of biological activities.8 Consequently, the development
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of an efficient and regioselective protocol to produce vicinal iodoazides is a worthy
objective.
Vicinal iodoazides are generally synthesized by reactions of alkenes with IN3.9-11
Because of the explosive character, IN3 is conventionally generated in situ by using
different combinations of azido and iodide sources in the presence of an oxidant.
Notably, depending on the reaction conditions and the reagent combinations used, the
in situ generated IN3 may undergo homolytic or heterolytic cleavage, which can lead
to anti-Markovnikov addition (radical pathway) or Markovnikov addition (via a cyclic
iodonium ion mechanism) products in reactions with asymmetric alkenes, respectively.
For example, using CAN as an oxidant, reaction with NaN3 and NaI gave exclusively
anti-Markovnikov addition product.12 Such are also the cases using combinations of
NaN3/NaI/oxone and NaN3/KI/NaIO4 (Scheme 1).13,14 In contrast, Markovnikov
addition reaction occurs when employing combinations of NaN3/I2, TMSN3/IPy2BF4,
TMSN3/Et4NI/PhI(OAc)2 and polymer-bound IN3 (Scheme 1).15-18 While much
progress has been made, these methods suffer from certain drawbacks such as usage
of “expensive” reagents and a large excess of oxidant. Consequently, a mild and
practical method that involves less toxic reagents and minimizes waste is of
importance.
(a) NaN3/I2
(b) TMSN3/IPy2BF4
(c) TMSN3/Et4NI/PhI(OAc)2
(d) polymer-bound IN3
(a) NaN3/NaI/CAN
(b) NaN3/NaI/oxone
(c) NaN3/KI/NaIO4
R3
I
N3
R3
N3
R1
R2
R3
I
R1
R2
R1
R2
Markovnikov addition
anti-Markovniv addition
Scheme 1. Azidoiodination of alkenes under different conditions
Toward this end, we describe herein our efforts to apply electrochemistry to
achieve oxidative azidoiodination of alkenes. To the best of our knowledge, there is
only one report of the electrochemical introduction of the azido unit onto an alkene
double bond. Thus, the anodic oxidation of enol ethers and enamide in methanol
containing 0.17 M of Et4NOTs as supporting electrolyte in the presence of NaN3
brought about azidomethoxylation and gave the corresponding acetal and
2

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N,O-acetal.19 Notably, in this electrochemical azidomethoxylation, the addition of an
azido group was observed to take place regioselectively at the β-position of the enol
ether or enamide via a radical mechanism (Scheme 2).
As a continuation of our ongoing program involving halide-mediated
electrochemical synthesis, we hypothesized that the electrochemical oxidation of
iodide ion ought to form molecular iodine, which may in situ undergo reaction with
NaN3 to afford IN3. Thereafter an azidoiodination reaction with an alkene ought to
provide the corresponding iodoazides.
Herein, we report an efficient electrochemical method for the regioselective
synthesis of vicinal iodoazides. In the protocol, IN3 is generated electrochemically in
situ, avoiding the utilization of external oxidants or corrosive molecular iodine and is
therefore environmentally benign. In addition, quite different from the
electrochemical azidomethoxylation referred to above, our protocol proceeds via a
cyclic iodonium mechanism to afford Markovnikov addition products exclusively
(Scheme 2).
Previous work: direct electrochemical azidonation
NaN3, Et4NOTs /
MeOH, CCE
MeO
R1
R1
R2X
N3
R2X
via an radical pathway
X = O, NH
This work: Indirect electrochemical azidoiodination
N3
R1
R2X
R1
NaN3/NaI/MeOH, CCE
I
R2X
via an cyclic iodonium
intermediate
X = CH2, O, NH
Scheme 2. Electrochemical azidoiodination of alkenes
Results and Discussion
I
N3
OMe
azido and iodide sources
+
+
N3
LiClO4 (0.1 M) in solvent
graphite anode and cathode
I
I
3a
1a
4a
2a
3

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Scheme 3. Conditional optimization of azidoiodination of p-methylstyrene 1a
We commenced our studies by using p-methylstyrene (1a) as model substrate
and a combination of NaN3/NaI as the IN3 precursor (Scheme 3 and Table 1).
Constant current electrolyses were performed at 15 mA/cm2 in an H-type cell using
two graphite plates as the working electrode and cathode. Given the fact that the ratio
of the IN3 precursor to the alkene and the nature of solvent influence the
azidoiodination reaction of alkenes, the ratio of styrene and NaN3/NaI was initially
investigated. When 1 mmol of 1a, 1.2 equiv of NaN3 and 1.2 equiv of NaI was used,
the Markovnikov addition-type adduct 2a was obtained exclusively, albeit in but a 34%
yield (Table 1, entry 1). Based on the extensive work of Hassner and coworkers,9-11
the formation of this Markovnikov addition-type adduct indicates that the
electrochemical azidoiodination of alkenes may involves the heterolytic cleavage of
-
IN3 to iodonium (I+) and azido anion (N3 ). Increasing of the ratio resulted in a
dramatic improvement of yield to 63% and 73% when the azido and iodide source
increased to 1.5 equiv and 2 equiv of styrene (Table 1, entries 2 and 3). A further
increase to 3 equiv of NaN3/NaI did not improve the yield (Table 1, entry 4).
Therefore, 2 equiv of NaN3/NaI to one equiv of styrene was the ratio of choice.
Solvent screening demonstrated that MeOH played a crucial role for the
Markovnikov addition-type azidoiodination reaction. The presence of water in
methanol turned out to give a slightly lower yield (65% vs 73%; Table 1, entry 5).
When MeCN was used as a solvent, an anti-Markovnikov regioisomer 3a was also
isolated in 18% yield, along with the desired adduct 2a (22% yield) (Table 1, entry 6).
We assume that the formation of anti-Markovnikov iodoazides involves a radical
pathway and that the electrochemically generated IN3 in CH3CN may undergo both
homolytic and heterolytic cleavage. In the case of CF3CH2OH, due to the low
solubility of NaN3, most of the starting styrene was recovered (Table 1, entry 7).
Next, the combination of NaN3 and different iodide sources were evaluated for
the azidoiodination reaction. It was observed that all of the iodide salts tested proceed
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smoothly, albeit in a slightly lower yields than that with NaI (Table 1, entries 3 and
8-11). For example, when KI was used, adduct 2a was obtained in 50% yield; it
changed to 66%, 55% and 61% when the iodide sources were NH4I, Et4NI and
n-Bu4NI, respectively. Interestingly, when TMSN3, instead of NaN3, was used as the
azido source, 1-(2-iodo-1-methoxyethyl)-4-methylbenzene, 4a, was isolated
exclusively in 35% yield (entry 12). The formation of 4a may result from the
nucleophilic attack of methoxide (generated from cathodic reduction of methanol) to
the cyclic iodonium. Finally, it was observed that room temperature was preferable for
the azidoiodination reaction since the yields of 2a decreased to 55% when the reaction
was performed at 0 oC and to 27% when carried out at 60 oC (entries 13-14).
Based on the results described above, we conclude that the optimal reaction
conditions call for using NaI and NaN3 as the IN3 precursor and a 2:1 ratio of
NaN3/NaI to alkene. The reaction is best performed in a divided cell using methanol
as the solvent.
Table 1. Optimization of the model reaction.
Entry
Substrate to
reagent ratio
Solvent
I-source
Temperature
(oC)
Yield of
2a (%) b
-
(1a: I-: N3 )
1:1.2:1.2
1:1.5:1.5
1:2:2
MeOH
MeOH
NaI
NaI
NaI
NaI
NaI
25
25
25
25
25
34
63
73
70
65
1
2
3
4
5
MeOH
1:3:3
MeOH
1:2:2
MeOH +
H2O ( v: v=
5: 1)
1:2:2
1:2:2
MeCN
NaI
NaI
25
25
22 c
0
6
7
CF3CH2OH
5

ACCEPTED MANUSCRIPT
1:2:2
1:2:2
1:2:2
1:2:2
1:2:2
1:2:2
1:2:2
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
KI
NH4I
Et4NI
n-Bu4NI
NaI
25
25
25
25
25
0
50
66
55
61
8
9
10
11
12
13
14
d
-
NaI
55
27
NaI
60
a Reaction conditions: 1a (1.0 mmol), NaN3 and NaI in 12 mL of solvent, divided cell,
current density of 15 mA/cm2, graphite plate anode and cathode, LiClO4 (0.1 M) was
added as a conducting salt.
b 1H NMR yield, using trimethoxybenzene as the internal standard.
c Along with 18% yield of 3a
d Me3SiN3 was used as the azido source and 4a was isolated in 35% yield.
With the optimized reaction conditions in hand, we then examined the scope and
limitations of the azidoiodination reaction using these conditions. As shown in Table 2,
azidoiodination of styrene derivatives 1b-h proceeded smoothly and the
corresponding adducts 2b-h were obtained. It was observed that substrates containing
electron rich substituents lead to significantly higher yields than those bearing
electron withdrawing groups. For example, when p-methoxystyrene was subjected to
the reaction conditions, adduct 2c was obtained in 55%. However, the electron
deficient fluoro-substituted styrene 1d gave very low yield of 2d (20%) under exactly
conditions. In addition, para-substituted adducts afford a higher yield than its
ortho-substituted counterpart (note 2e and 2g with yields of 40% vs. 10%). In the case
of 2-phenylpropene 1h, adduct 2h was obtained in 44% yield. For the unactivated
terminal alkene 1i, the desired 2i was isolated in a 47% yield.
Internal alkenes were also investigated. Cyclohexene gave a 30% yield of
trans-addition product 2j. When cis-phenyl-1-propene 1k was subjected to
6

ACCEPTED MANUSCRIPT
electrochemical azidoiodination with NaN3/NaI under the standard conditions, a
mixture of regioisomers, the Markovnikov product 2k and anti-Markovnikov product
3k, were obtained in a 40% combined yield. Strangely, when trans-phenyl-1-propene
1l was used as a substrate, the adduct 2l was not detected, whereas the starting 1l
disappeared. In the case of cis-stilbene, a 1:1.2 diastereomeric mixture of
1-azido-2-iodo-1,2-diphenylethane, 2m was isolated in a combined 50% yield. The
same diastereomeric ratio resulted when trans-stilbene was exposed to electrolysis in
the presence of NaN3 and NaI and 55% yield of diastereomers 2m was obtained. The
literature reports that trans- and cis-stilbene afford erythro- and threo-2m,
20
respectively, under conventional chemical conditions. That anti-selectivity was not
observed under our conditions using trans- and cis-stilbene, suggests that the expected
intermediate cyclic iodonium is not stable and that ring opening occurs to give an
intermediate carbon cation, thereby leading to partial syn-addition. When alkenes
containing a heteroatom appended directly to the alkene group were subjected to
electrolysis under the standard conditions (using methanol alone as solvent), the
reaction also occurred, but with lower yield. For example, when tetrahydropyran 1o
and 1-vinylpyrrolidin-2-one 1p were used, adducts 2o and 2p were isolated in 17%
and 25% yields, respectively.
Table 2. Scope of alkene using methanol as solvent a
I
R1
N3
R1
LiClO4 (0.1 M) / MeOH
divided cell, rt
R3
R3
NaN3
NaI
+
+
R2
R2
1
2
7

ACCEPTED MANUSCRIPT
Entry
Yield (%)b
Alkenes 1
Products 2
N3
2a: R1 = p-Me
2b: R1 = H
2c: R1 = p-OMe
2d: R1 = p-F
2e: R1 = p-Cl
2f: R1 = p-Br
2g: R1 = o-Cl
1a: R1 = p-Me
1b: R1 = H
1c: R1 = p-OMe
1d: R1 = p-F
1e: R1 = p-Cl
1f: R1 = p-Br
1g: R1 = o-Cl
65
55
55
20
40
40
1
2
3
4
5
6
7
R1
R1
I
10
N3
44
2h
1h
8
9
I
N3
47
30
1i
2i
I
N3
1j
2i
10
I
N3
I
40, 2k:3k = 1:1
+
1k
1l
11
12
13
N3
I
2k
3k
N3
trace
2l
I
N3
N3
I
50, dr: 1: 1.2
55, dr: 1:1.2
Ph
Ph
1m
Ph
Ph
Ph
Ph
Ph
Ph
I
2m
N3
N3
14
1n
Ph
Ph
Ph
Ph
I
I
2m
I
15
16
1o
2o
17
25
O
N3
O
N
1p
O
2p
O
N
I
N3
a
Reaction conditions: alkene 1 (1.0 mmol), NaN3 (2.0 mmol) and NaI (2.0 mmol) in
12 mL of methanol, divided cell, current density of 15 mA/cm2, graphite plate anode
and cathode, LiClO4 (0.1 M) was added as a conducting salt.
b Isolated yield after column chromatograph
Due to the lower yields for some of the substrates (such as 1d and 1g), further
8

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optimization was carried out. We found that an improved yield of 2 was obtained
when a mixture of methanol and water (v:v = 5:1) was employed as the solvent under
otherwise identical electrolytic conditions. For example, 2d, 2e and 2g were isolated
in 47%, 70% and 40% yields, respectively, much higher than that obtained when
using methanol alone as the solvent. Interestingly, under the modified conditions,
(z)-1-propenylbenzene 1k only gave the Markovnikov trans-addition product 2k in a
yield of 20%, and 1l afforded the desired adduct 2l in a yield of 32% (Table 3).
Although the exact reason for the regioselective reaction of 1k in MeOH/H2O is not
clear at the presence, we assume that the polarity of the solvent may play an important
role, higher polarity of a mixed solution benefits heterolytic cleavage of IN3 and leads
to Markovnikov addition product, 2k. This observation can be demonstrated by the
azidoiodination reactions of 1a in CH3CN and MeOH. In the former, both 2a and 3a
were isolated simultaneously, whereas only 2a was produced in MeOH (see entries 3
and 6 in Table 1). Under the modified conditions, improved yields of 2o and 2p were
also obtained. It is worth mentioning that our results differ from those reported by
Nishiguchi et al.19 Thus, the direct electrochemical oxidation of 1o and 1p in
methanol
using
Et4NOTs
as
a
conducting
salt
afforded
and
3-azido-2-ethoxy-tetrahydro-2H-pyran
(3)
1-(2-azido-1-methoxyethyl)pyrrolidin-2-one (5) wherein the azido group was
introduced into the β-position (Scheme 4).
Table 3. Scope of alkene using aqueous methanol as solvent a
9

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I
LiClO4 (0.1 M)
MeOH / H2O
R1
N3
R1
R3
R3
NaN3
NH4I
+
+
R2
divided cell, r.t.
R2
1
2
N3
N3
N3
I
I
I
F
Cl
Cl
2d (47%)
2g (40%)
2e (70%)
N3
I
N3
N3
N
I
O
O
N3
I
I
2o (35%)
2k (20%)
2l (32%)
2p (65%)
a Reaction conditions: alkene 1 (1.0 mmol), NaN3 (1.5 mmol) and NH4I (1.5 mmol) in
12 mL of mixed solvent of methanol and water (v:v = 5:1), divided cell, current
density of 15 mA/cm2, graphite plate anode and cathode, LiClO4 (0.1 M) was added
as a conducting salt.
I
N3
NaN3, NaI
NaN3
Et4NOTs/MeOH
CCE
LiClO4/MeOH-H2O
CCE
O
N3
O
O
OMe
2o
3
1o
NaN3
NaN3, NaI
O
O
N3
N
O
N
N
Et4NOTs/MeOH
CCE
I
LiClO4/MeOH-H2O
CCE
N3
MeO
5
2p
1p
Scheme 4. Regioselectivity
To gain insight into the mechanism of the electrochemical azidoiodination of
alkenes, we performed cyclic voltammetry experiments involving the alkenes and the
IN3 precursors. It was found that the oxidation peak potentials of NaI and NaN3 were
0.45 V and 0.85 V (vs Ag/AgNO3 in 3 M KCl), which indicates that NaI is
10

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electrochemically much easier to oxidize than NaN3. That no oxidation peak was
observed for styrene 1a up to the oxidation potential of the solvent methanol clearly
demonstrates that styrene ought not to be oxidized under the standard conditions.
In addition, for the conventional chemical azidoiodination of alkenes, it has been
demonstrated that radical pathway gives anti-Markovnikov addition products, while
Markovnikov addition proceeds via a cyclic iodonium intermediate. Based on our
cyclic voltammetry measurements and literature reports, we propose a mechanism
shown in Scheme 5 for the electrochemical synthesis of vicinal iodoazides. As
illustrated, the reaction begins with the anodic oxidation of iodide to generate
molecular iodine, which reacts with azido ion to produce IN3. When using polar
solvents such as methanol and water, the in situ generated IN3 reacts predominantly as
a source of I+ to form cyclic iodonium intermediate 6 whose capture by azide at the
more substituted carbon affords the Markovnikov type addition product 2.
2 N3
-2e
I2
2I
2 IN3
+
I
N3
-2e
I
N3
I
N3
Ar
Ar
Ar
I
6
2
1
Scheme 5. Plausible mechanism for the regioselective azidoiodination of alkenes
Conclusion
In summary, a new and efficient electrochemical method for the synthesis of
vicinal iodoazides has been developed. The procedure uses a constant current
electrolysis of NaN3 and NaI in the presence of alkenes in an H-type cell employing
methanol as the solvent. A wide range of substrates proved to be compatible with the
protocol, delivering the products in a Markovnikov fashion. The results suggest that
the reaction proceeds via a cyclic iodonium intermediate. Further application of these
11

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ideas and results to other types of reactions is underway in our laboratory.
4. Experimental
4.1 Instruments and reagents
1
NMR spectra were recorded using a 400 MHz spectrometer (400 MHz H
frequency, 100 MHz 13C frequency). Chemical shifts are given as δ values
(internal standard: TMS). Coupling constants are reported in Hz. Starting materials
and solvents were obtained from commercial sources and used without further
purification. Products were purified by chromatography on silica gel (petroleum
ether/EtOAc).
4.2 Typical procedure for the electrochemical synthesis of 2
An H-type cell with a G4-fritted glass as a diaphragm was equipped with a
carbon anode (2.0 × 1 cm2) and a carbon cathode (2.0 × 1 cm2) and connected to a DC
regulated power supply. To the anodic compartment was added alkene (1 mmol),
NaN3 (2 mmol), iodide salt (2 mmol) and 12 mL of methanol dissolved in 0.1 M
LiClO4, whereas the cathodic compartment was added only 12 mL 0.1 M LiClO4. The
mixture was electrolyzed using constant current conditions (~15 mA/cm2) at room
temperature under magnetic stirring. When TLC analysis indicated that the
electrolysis was complete (witnessed by the disappearance of the amide), the solvent
was removed under reduced pressure. The residue was poured into a saturated
aqueous solution of Na2S2O3 and the product was then extracted with DCM (3×20
mL), dried over MgSO4, and concentrated in vacuo. The residue was purified by
column chromatography on silica gel using a mixture of petroleum ether/EtOAc (v : v
= 150 : 1) as eluent to afford the desired pure product.
1-(1-Azido-2-iodoethyl)-4-methylbenzene (2a) 15
Yield: 186 mg, 65%; yellow oil; 1H NMR (400 MHz, CDCl3): δ 2.39 (s, 3H), 3.40 (d,
J = 7.2 Hz, 2H), 4.71 (t, J = 6.8 Hz, 1H), 7.21-7.26 (m, 4H); 13C NMR (100 MHz,
CDCl3): δ 8.4, 21.3, 67.0, 126.6, 129.8, 134.9, 139.1.
1-(1-Azido-2-iodoethyl)benzene (2b) 15
12

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Yield: 150 mg, 55%; colorless oil; 1H NMR (400 MHz, CDCl3): δ 3.42 (d, J = 6.8 Hz,
2H), 4.75 (t, J = 7.2 Hz, 1H), 7.34-7.46 (m, 5H); 13C NMR (100 MHz, CDCl3): δ 8.4,
67.2, 126.8, 129.1, 129.1, 138.0.
1-(1-Azido-2-iodoethyl)-4-methoxybenzene (2c) 21
Yield: 167 mg, 55%; colorless oil; 1H NMR (400 MHz, CDCl3): δ 3.38-3.40 (m, 2H),
3.84 (s, 3H), 4.70 (t, J = 6.8 Hz, 1H), 6.95 (d, J = 8.8 Hz, 2H), 7.27 (d, J = 8.8 Hz,
2H); 13C NMR (100 MHz, CDCl3): δ 8.5, 55.4, 66.7, 114.4, 128.0, 129.9, 160.03.
1-(1-Azido-2-iodoethyl)-4-fluorobenzene (2d)
Yield: 137 mg, 47%; colorless oil; 1H NMR (400 MHz, CDCl3): δ 3.38-3.40 (m, 2H),
13
4.73 (t, J = 7.2 Hz, 1H), 7.10-7.15 (m, 2H), 7.31-7.35 (m, 2H); C NMR (100 MHz,
CDCl3): δ 8.1, 66.3, 116.0, 116.2, 128.5, 128.6; IR (KBr) (cm-1): υ 2106, 1698, 1588,
1487, 1072, 1010,; HRMS (ESI) m/z calcd for C8H7FI (M-N3)+: 248.9576, found:
248.9574.
1-(1-Azido-2-iodoethyl)-4-chlorobenzene (2e) 21
1
Yield: 222 mg, 70%; yellow oil; H NMR (400 MHz, CDCl3): δ 3.38 (d, J = 6.4 Hz, 2H),
4.72 (t, J = 6.8 Hz, 1H), 7.28 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H) ; 13C NMR (100
MHz, CDCl3): δ 8.0, 66.3, 128.1, 129.3, 134.9, 136.4.
1-(1-Azido-2-iodoethyl)-4-bromobenzene (2f)
Yield: 137 mg, 39%; colorless oil; 1H NMR (400 MHz, CDCl3): δ 3.38 (d, J = 7.2 Hz,
13
2H), 4.71 (t, J = 6.8 Hz, 1H), 7.22 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 8.4 Hz, 2H); C
NMR (100 MHz, CDCl3): δ 7.9, 66.3, 123.1, 128.4, 132.3, 136.9; IR (KBr) (cm-1): υ
2106, 1603, 1510, 1230; HRMS (ESI): m/z calcd for C8H7BrI (M-N3)+: 308.8776,
found: 308.8769.
1-(1-Azido-2-iodoethyl)-2-chlorobenzene (2g)
1
Yield: 123 mg, 40%; colorless oil; H NMR (400 MHz, CDCl3): δ 3.33 (dd, J = 10.4
Hz, J = 8.8 Hz, 1H), 3.52 (dd, J = 10.4 Hz, J = 4.4 Hz, 1H), 5.24 (dd, J = 8.4 Hz, J =
13
4.0 Hz, 1H), 7.32-7.51 (m, 4H); C NMR (100 MHz, CDCl3): δ 7.2, 63.3, 127.6,
127.6, 130.0, 130.1, 132.7, 135.9; IR (KBr) (cm-1): υ 2109, 1473, 1443; HRMS (ESI)
m/z calcd for C8H9ClIN (M-N2+H)+: 279.9389, found: 279.9379.
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(2-Azido-1-iodopropan-2-yl)-benzene (2h)
1
Yield: 127 mg, 44%; colorless oil; H NMR (400 MHz, CDCl3): δ 1.91 (s, 3H), 3.49
(d, J = 10.8 Hz, 1H), 3.53 (d, J = 10.4 Hz, 1H), 7.35-7.47 (m, 5H); 13C R (100 MHz,
CDCl3): δ 17.7, 25.2, 65.1, 125.7, 128.3, 128.8, 140.8; IR (KBr) (cm-1): υ 2980, 2105,
1494, 1446; HRMS (ESI): m/z calcd for C9H10I (M-N3)+: 244.9827, found: 244.9826.
(3-Azido-4-iodobutyl)-benzene (2i)
Yield: 142 mg, 47%; colorless oil; 1H NMR (400 MHz, CDCl3): δ 1.86-2.10 (m, 2H),
2.69-2.87 (m, 2H), 3.31 (d, J = 6.0 Hz, 2H), 3.40-3.44 (m, 1H), 7.23-7.37 (m, 5H);
13C NMR (100 MHz, CDCl3): δ 8.3, 32.0, 36.2, 61.8, 126.4, 128.4, 128.7, 140.4; IR
(KBr) (cm-1): υ 3026, 2924, 2857, 2106, 1602, 1496, 1453; HRMS (ESI) m/z: calcd
for C10H13IN (M+H-N2)+: 274.0093, found: 274.0084.
1-Azido-2-iodocyclohexane (2j) 15
1
Yield: 77 mg, 30%; colorless oil; H NMR (400 MHz, CDCl3): δ 1.32-1.60 (m, 4H),
13
1.87-2.48 (m, 4H), 3.50-3.55 (m, 1H), 3.94-4.00 (m, 1H); C NMR (100 MHz,
CDCl3): δ .23.9, 27.1, 32.0, 33.4, 38.5, 67.2.
Cis-(1-Azido-2-iodopropyl)-benzene (2k)
Yield: 57 mg, 20%; colorless oil; 1H NMR (400 MHz, CDCl3): δ 1.78 (d, J = 7.2 Hz,
13
3H), 4.42 (quint, J = 6.8 Hz, 1H), 4.52 (d, J = 8.0 Hz, 1H), 7.32-7.45 (m, 5H); C
NMR (100 MHz, CDCl3): δ 25.7, 30.2, 73.6, 127.3, 128.9, 129.0, 136.9; IR (KBr)
(cm-1): υ2102, 1493, 1453, 763, 700; HRMS (ESI): m/z calcd for C9H10I (M-N3)+:
244.9827, found: 244.9825.
Trans-(1-Azido-2-iodopropyl)-benzene (2l) 22
Yield: 93 mg, 32%; colorless oil; 1H NMR (400 MHz, CDCl3): δ 1.90 (d, J = 6.8 Hz,
3H), 4.37 (quint, J = 6.4 Hz, 1H), 4.80 (d, J = 6.0 Hz, 1H), 7.35-7.45 (m, 5H); 13C
NMR (100 MHz, CDCl3): δ 23.5, 29.0, 72.7, 127.4, 128.9, 128.9, 137.4.
14

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(1-Azido-2-iodoethane-1,2-diyl)-dibenzene (2m,2n) d.r. =1:1.2 16
Yield: 197 mg, 65%; colorless oil; 1H NMR (400 MHz, CDCl3): δ 4.98 (d, J = 9.6 Hz,
1H), 5.15 (d, J = 9.2 Hz, 1H), 5.22 (d, J = 9.6 Hz, 1H), 5.26 (d, J = 9.2 Hz, 1H),
13
7.15-7.50 (m, 20H); C NMR (100 MHz, CDCl3): δ 34.4, 36. 8, 71.9. 72.8, 127.3,
127.7, 128.3, 128.5, 128.6, 128.7, 128.8, 129.1, 136.3. 137.7, 140.1, 140.2; IR (KBr)
(cm-1): υ 3031, 2103, 756.9, 698.
2-Azido-3-iodo-tetrahydro-2H-pyran (2o) 15
1
Yield: 87 mg, 35%; colorless oil; H NMR (400 MHz, CDCl3): δ 1.67-1.73 (m, 2H),
2.04-2.13 (m, 1H), 2.38-2.45 (m, 1H), 3.67-3.73 (m, 1H), 3.92-3.97 (m, 1H),
13
4.11-4.16 (m, 1H), 4.96 (d, J = 7.2 Hz, 1H); C NMR (100 MHz, CDCl3): δ 26.4,
27.4, 34.0, 66.2, 92.4.
1-(1-Azido-2-iodoethyl)pyrrolidin-2-one (2p)
1
Yield: 180 mg, 65%; yellow oil; H NMR (400 MHz, CDCl3): δ 2.07-2.14 (m, 2H),
2.46 (t, J = 8.0 Hz, 2H), 3.17 (t, J = 8.8 Hz, 1H), 3.31-3.45 (m, 3H), 5.82-5.86 (m,
1H); 13C NMR (100 MHz, CDCl3): δ 2.0, 18.1, 30.7, 41.3, 68.2, 175.8; IR (KBr)
(cm-1): υ 2958, 2108, 1697, 1413; HRMS (ESI): m/z calcd for C6H9INO (M-N3)+
237.9729, found: 237.9729.
1-(1-Azido-2-iodoethyl)-4-methylbenzene (2a) and 1-(2- Azido-1-iodoethyl)-4-
methylbenzene (3a) 12
Yield: 114.8 mg, 40%; yellow oil; 1H NMR (400 MHz, CDCl3): δ 2.53 (s, 3H), 2.39 (s,
7H), 3.40 (d, J = 6.8 Hz, 4.2H), 3.95 (d, J = 8.0 Hz, 2H), 4.71 (t, J = 6.8 Hz, 2.1H),
5.172 (t, J = 7.6 Hz, 1H), 7.17 (d, J = 8 Hz, 2H), 7.24 (m, 9H), 7.34 (d, J = 8 Hz, 2H).
1-(2-Iodo-1-methoxyethyl)-4-methylbenzene (4a) 23
1
Yield: 96 mg, 35%; H NMR (400 MHz, CDCl3): δ 2.40 (s, 3H), 3.33 (s, 3H),
3.32-3.38 (m, 2H), 4.30-4.33 (m, 1H), 7.21-7.25 (m, 4H); 13C NMR (100 MHz,
CDCl3): δ 10.9, 21.4, 57.3, 83.4, 126.5, 129.5, 136.8, 138.3.
15

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(1-azido-2-iodopropyl)-benzene (2k) and (2-azido-1-iodopropyl)-benzene (3k) 22
1
Yield: 114 mg, 40%, yellow oil; H NMR (400 MHz, CDCl3): δ 1.26 (d, J = 6.4 Hz,
4H), 1.54 (d, J = 6.4 Hz, 3H), 1.78 (d, J = 6.8 Hz, 6H), 3.81-3.88 (m, 1H), 3.94-4.01
(m ,1H), 4.24-4.31 (m, 2H), 4.52 (d, J = 8.4 Hz, 2H), 4.96 (d, J = 8 Hz, 1H), 5.01 (d, J
= 8 Hz, 1H), 7.29-7.36 (m, 11H), 7.38-7.43 (m, 12H).
Acknowledgements
This work was supported by grants from the National Natural Science Foundation of
China (No. 21272021, 21472011) and the national key research and development
program (2016YFD0400801)
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