Fluorocyclization of Vinyl Azides for the Formation of 3-Azido Heterocycles

Article abstract of DOI:10.1002/asia.202001175

3-Azido saturated heterocycles are important for therapeutic-development but challenging to prepare. Disclosed herein is a novel synthetic strategy for 3-azido heterocycles via fluorocyclization of the easily available vinyl azides. This transfor-mation proceeded under mild conditions and provided a wide range of 3-azido heterocycles in good to excellent yields. Notably, the azido group plays an indispensable role to promote rapid and regioselective fluorocyclization. Moreover, the protocol was highlighted by gram-scale synthesis and further synthetic transformations.

Full text of DOI:10.1002/asia.202001175

DOI: 10.1002/asia.202001175
Communication
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
Fluorocyclization of Vinyl Azides for the Formation of 3-Azido
Heterocycles
+
[a]
+ [b]
+ [b]
[b]
[b]
Diangang Bai , Linxuan Li , Xiaomeng Li , Ying Lu, Yong Wu,*
[b]
[a, b]
Bhoomireddy Rajendra Prasad Redd, and Yongquan Ning*
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
Abstract: 3-Azido saturated heterocycles are important for
therapeutic-development but challenging to prepare. Dis-
closed herein is a novel synthetic strategy for 3-azido
heterocycles via fluorocyclization of the easily available
vinyl azides. This transfor-mation proceeded under mild
conditions and provided a wide range of 3-azido hetero-
cycles in good to excellent yields. Notably, the azido group
plays an indispensable role to promote rapid and regiose-
lective fluorocyclization. Moreover, the protocol was high-
lighted by gram-scale synthesis and further synthetic trans-
formations.
Functionalized saturated heterocycles are ubiquitous structural
elements in many natural products, bioactive compounds, and
[1]
pharmaceuticals. Among these, 3-azido variants are more
attractive as the azido group is a useful linker in bioorthogonal
[
2]
chemistry, and are also frequently found in many biologically
Figure 1. Bioactive molecules containing 3-azido heterocycles.
[3]
active molecules (Figure 1). Moreover, they have also been
used as key intermediates in the development of new
pharmaceuticals, for instance, Fondaparinux sodium (Fig-
[4]
[3c]
ure 1). These immense biological properties motivate chem-
ists to develop efficient synthetic methods to access 3-azido
heterocycles. Typical access of these scaffolds relies on post
functionalization of parent heterocycles. For example, Lu and
co-workers developed a polarity-reversed addition cascade of
[5]
2
,3-dihydrofuran with imine, and TMSN (Figure 2a). On the
3
other hand, Bian et al. established a multi-step procedure for
the synthesis of 3-azido pyrrolidines starting from 2,5-dihydro-
[6]
pyrroles (Figure 2a). However, these post functionalization
strategies are not practical due to nasty side reactions of
sensitive functional groups, thus limiting its broad applications.
Therefore, the discovery of new methods to construct 3-azido
heterocycles that might not rely on parent heterocycles are
especially attractive and also highly desirable. Vinyl azides are a
class of structurally unique and synthetically useful functional-
ized alkenes and have been widely explored in organic
Figure 2. Strategies for the synthesis of 3-azido hereocycles.
utilized vinyl azides as key precursors for the synthesis of azido-
[7]
[8]
[9]
synthesis. Recently, López, and Xu groups independently
cycloalkenes and 2-azido-3,4-dihydropyrans, respectively.
However, the synthesis of 3-azido saturated heterocycles from
vinyl azides remains unknown to date and therefore the
development of an efficient method for their synthesis is greatly
desirable.
+
[
a] D. Bai, Y. Ning
School of Chemistry and School of Chemistry and Life Science, Anshan
Normal University, Anshan, 114005 (P. R. China)
+
+
In recent years, the fluorocyclization of alkenes has
continued to attract increasing attention for the validation of
[
b] L. Li, X. Li, Y. Lu, Y. Wu, B. Rajendra Prasad Redd, Y. Ning
Department of Chemistry, Northeast Normal University, Changchun 130024
(
P. R. China)
[10]
saturated fluorinated heterocycles. In line with our continued
E-mail: wuy651@nenu.edu.cn
ningyq508@nenu.edu.cn
[11]
efforts in the chemistry of vinyl azides, we wondered whether
+
[
] D. Bai, L. Li and X. Li are equal to this work.
vinyl azides with appropriately positioned O/N-nucleophiles are
Chem Asian J. 2020, 15, 1–6
1
© 2020 Wiley-VCH GmbH
��
These are not the final page numbers!

Communication
involved in fluorocyclization to build 3-azido saturated hetero-
cycles. Herein, we disclose the first successful process that
delivers 3-azido saturated heterocycles upon fluorocyclization
of vinyl azides (Figure 2b). In this event, the azido group serves
not only as a useful functional group but also plays an
indispensable role by developing a charge difference in C=C to
enhance the reactivity of electrophilic addition that led to
promote 5-endo-cyclization. The azido group with many
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
[7]
possibilities for further modification and the potency of a
fluorine atom to modulate the chemical/biological properties of
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
[12]
molecules; such derivatives would constitute a new chemical
space for exploration in drug discovery.
To test the proposed strategy, we began our investigation
by studying the oxyfluorination reaction of 1d (Table 1). After
intensive examination, we found that the desired 3-azido
heterocycle 2d was obtained in 98% yield when using
iodobenzene diacetate (PIDA, 1.5 equiv) as oxidant and pyridi-
ne·HF complex (Py·HF, 2.0 equiv) as fluorine source in dichloro-
[
13]
methane (DCM) at 0°C (entry 1).
Replacing PIDA with
iodosobenzene bis(trifluoroacetate) (PIFA) or iodosylbenzene
[
a]
Scheme 1. Oxyfluorination. [a] Reaction conditions: 1 (0.2 mmol), PIDA
0.3 mmol, 1.5 equiv), and Py·HF (0.4 mmol, 2.0 equiv) in 2 mL of DCM at
(
PhIO) resulted in lower yields (entries 2, 3). The use of oxidants
other than hypervalent iodines led to no reaction (entries 4 and
). The desired product was not observed when using inorganic
(
b
c
0°C for 1 min. Inseparable mixture. Yields refer to 1H-NMR with respect
3
to the PhCF standard, not isolated due to the volatile nature of compounds.
e
5
d
Isolated yield is less owing to low boiling points. 1f or 1h (0.5 mmol),
PIDA (0.75 mmol, 1.5 equiv), and Py·HF (1.0 mmol, 2.0 equiv) in 2 mL of
DCM at 0°C for 1 min; after simple handling without isolation, added
phenylacetylene (1.2 equiv), and CuI (10 mol%) in 2 mL of DMSO at rt for
6 h.
fluorinating agents (AgF and CsF) and Selectflour, although a
trace amount of 2d was obtained with Et N·HF (entries 6–8).
3
Switching the solvent from DCM to chlorobenzene or
acetonitrile gave the product in a slightly lower yield, while the
reaction was shutdown in DMF (entries 9–11). The reaction also
proceeded equally at either room temperature or below 0°C,
albeit produced 2d in somewhat reduced yields (entries 12–14).
Having developed the optimum conditions for the oxy-
fluorination of vinyl azides, the scope of the reaction evaluated
first with a range of linear homoallylic alcohols (Scheme 1). The
oxyfluorination of mono- or different substituents at the β-
carbon of alkene affords the diastereomeric mixture of products
in overall high yields (2a–2c, 75–83% yields, 1.2:1–1.4:1). Vinyl
azides bearing diphenyl or dibenzyl groups at the β-carbon of
alkene dispense the corresponding products in excellent yields
(2d, 2e). Unsubstituted homoallylic alcohol (1f) also partici-
pated well. Similarly, cyclic homopropargylic alco-hols were also
equally undergone effective fluorocyclization, giving the desired
spiro-products 2g–2l in 70–95% yield. However, the com-
pounds 2f–2l were not enough stable to isolate, and the
formation of these compounds was confirmed by derivatization
of 2f and 2h.
[a]
Table 1. Optimization of the reaction conditions.
[b]
Entry
oxidant
‘F’ source
solvent
T [°C]
yield of 2d [%]
1
2
3
4
PIDA
PIFA
PhIO
Py·HF
Py·HF
Py·HF
Py·HF
Py·HF
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
PhCl
0
98
23
48
0
0
0
0
0
0
0
0
0
H
2
O
S
2
5
K
2
2
O
8
0
6
7
8
9
PIDA
PIDA
PIDA
PIDA
PIDA
PIDA
PIDA
PIDA
PIDA
Et ·HF
AgF/CsF
Selectflour
Py·HF
Py·HF
Py·HF
Py·HF
Py·HF
Py·HF
3
trace
0
0
82
70
0
10
CH CN
3
0
0
1
1
1
1
2
3
DMF
DCM
DCM
DCM
25
À 20
À 45
79
81
80
14
a
b
Reaction conditions: 1d (0.2 mmol), oxidant (0.3 mmol, 1.5 equiv), and ‘F’ source (0.4 mmol, 2.0 equiv) in 2 mL of solvent for 1 min. Isolated yield.
Chem Asian J. 2020, 15, 1–6
www.chemasianj.org
2
© 2020 Wiley-VCH GmbH
��
These are not the final page numbers!

Communication
Encouraged by the above results, we next applied this
strategy to homoallylic sulfonamides that enable the amino-
fluorination (Scheme 2). However, the high temperature (typi-
cally room temperature) required to afford the best efficiency.
The influence of having a substitution pattern of the aryl
sulfonyl protecting group on the nitrogen atom was firstly
examined (6a–6i). The electronic nature and position of
substituents on the benzene ring did not influence the amino-
fluorination pro-cess, and all were delivered the azaheterocycles
in excellent yields (6a–6i). The formation of pyrrolidine
structure was confirmed by single-crystal X-ray diffraction
analysis of 6d (CCDC: 1978654). Similarly, amines bearing
naphthyl-, heteroaryl-, and methyl sulfonyl groups were also
smoothly participated in the cyclization (6j–6l). Moreover,
amine tethered on secondary or tertiary carbon has also
proceeded well and afforded the desired products in ex-cellent
yields (6m and 6n). Subsequently, we studied the possibility of
extending the aminofluorination reaction to the synthesis of
piperidine derivatives. Under the standard conditions, a range
of piperidine derivatives (6o–6x) has also been framed well
without difficulty.
The practicability and effectiveness of this strategy were
demonstrated by the gram-scale synthesis of 2d and 6a
(Scheme 3). To further prove the utilities of these com-pounds,
we performed a series of synthetic manipulations. For example,
the azido group in the products 2d and 6a were easily
transformed to 1,2,3-triazoles (7–9, 11) through base-mediated
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
[14–16]
1,3-dipolar cycloaddition with alkynes.
Meanwhile, the
representative products 2d and 6a are readily converted to the
[17]
respective amines (10, 12) by reduction with LiAlH4. Further,
pyrrolidine 6a was effectively converted to 3-pyrrolidone 13
simply treated by HCl (1.0 M).
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
To determine the role of the azido group in fluorocycliza-
tion, we performed the control experiments with homoallylic
alcohols lacking an azido group (Scheme 4a). No desired
product 15’ was observed under standard conditions, even if
the reaction time was extended to 12 h, albeit trace amount of
14’ was detected. The reason behind the higher activity of vinyl
azides may be due to the fact that the azido group acts as an
electron-donating group which is capable of polarizing the C=C
double bond and then readily attacted by electrophilic
[7]
species. Based on these experimental results and literature
[18]
precedents,
the possible reaction pathway is proposed
(
Scheme 4b). Initially, PhIF ·HF is generated in situ from the
2
reaction of PIDA and Py·HF. Then, the regioselective vicinal
iodofluorination of vinyl azide 1d with PhIF ·HF occurs to form
2
the intermediate I. Subsequently, the intramolecular nucleo-
philic attack of the CÀ I bond of I by the tethered O/N-
nucleophile results in the formation of a tetrahydrofuranium
Scheme 3. Gram-scale synthesis and further transfor-mations. [a] Reaction
conditions: [a] 2d (0.5 mmol), phenylacetylene (0.6 mmol, 1.2 equiv), and
CuI (0.05 mmol, 10 mol%) in 2 mL of DMSO at rt for 6 h; [b] 2d (0.5 mmol),
2
2
-(trimethylsilyl)phenyl triflate (0.6 mmol), and CsF (2.0 mmol, 4.0 equiv) in
mL of CH CN at rt for 24 h; [c] 2d or 6a (0.5 mmol), and diethyl
3
acetylenedicarboxylate (0.7 mmol, 1.4 equiv) in neat at 100°C for 30 min; [d]
2d or 6a (0.5 mmol), and LiAlH (0.6 mmol, 1.2 equiv) in 10 mL of THF at
4
[a]
Scheme 2. Aminofluorination. [a] Reaction conditions: 5 (0.2 mmol), PIDA
0.3 mmol, 1.5 equiv), and Py·HF (0.4 mmol, 2.0 equiv) in 2 mL of DCM at rt
25°C for 3 h; [e] 6a (0.5 mmol), and 1.0 M HCl (2.0 mmol, 4.0 equiv) in 2 mL
b
(
of DCM at rt for overnight. 110°C for 10 min. Yields are of isolated
b
for 1 min. Inseparable mixture. Yields are of isolated products.
products.
Chem Asian J. 2020, 15, 1–6
www.chemasianj.org
3
© 2020 Wiley-VCH GmbH
��
These are not the final page numbers!

Communication
7
1
3
.2 Hz, 4H), 7.24 (dt, J=10.8, 7.2 Hz, 2H), 4.22 (dd, J=16.2, 10.2 Hz,
H), 3.95 (dd, J=20.4, 10.8 Hz, 1H), 3.23 (dd, J=19.8, 14.4 Hz, 1H),
.05 (dd, J=17.4, 13.8 Hz, 1H). 13 C NMR (150 MHz, CDCl3) δ 144.2,
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
144.1, 128.5, 128.4, 127.5, 127.4, 125.7, 125.6, 112.9 (d, J=224.6 Hz),
88.7 (d, J=2.1 Hz), 74.0 (d, J=30.9 Hz), 49.7 (d, J=25.5 Hz). 19F
À 1
NMR (470 MHz, CDCl3) δ À 110.88–(À 111.08) (m). IR (film, cm ):
2
124, 1339, 1260, 1166, 990, 867, 743, 706.
1
3-azido-3-fluoro-1-tosylpyrrolidine (6a). Colorless oil; H NMR
600 MHz, CDCl ) δ 7.72 (d, J=7.8 Hz, 2H), 7.35 (d, J=7.8 Hz, 2H),
(
3
3
1
1
.61 (ddd, J=17.4, 12.0, 1.2 Hz, 1H), 3.53 (ddd, J=12.0, 8.4, 3.6 Hz,
H), 3.47–3.36 (m, 2H), 2.45 (s, 3H), 2.35–2.28 (m, 1H), 2.17–2.08 (m,
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
13
H). C NMR (150 MHz, CDCl ) δ 144.2, 133.1, 129.9, 127.6, 110.1 (d,
3
19
J=223.4 Hz), 55.8 (d, J=30.6 Hz), 46.2, 35.6 (d, J=26.6 Hz), 21.6.
F
À 1
NMR (470 MHz, CDCl ) δ À 114.68–(À 114.84) (m). IR (film, cm ):
3
3446, 2963, 2125, 1508, 1339, 1261, 1163, 1094, 826, 626.
Scheme 4. Control experiments and proposed mechanism.
Acknowledgements
This work was supported by Postdoctoral Innovation Talent
Support Program (BX20200079) and the Fundamental Research
Funds
ion (II). Following the proton elimination from II in the form of
HF produced the final product 2d.
In summary, a novel strategy for the synthesis of 3-azido
saturated heterocycles via the fluorocyclization of vinyl azides
has been developed. This method furnishes a broad range of 3-
for
the
Central
Universities
(2412020QD005,
2412020FZ006).
azido oxa/azaheterocycles that are typically difficult with post Conflict of Interest
functionalization. The protocol is viable for large-scale synthesis,
and further synthetic derivatization demonstrates the useful-
ness of these products. Given the importance of azido and
fluoro heterocycles in drug discovery and the rich chemistry of
the azido group, the cyclization method described here is
expected to have broad applications in medicinal research and
organic synthesis methodology can find potential applications
in the future.
The authors declare no conflict of interest.
Keywords: Vinyl Azides · Fluorocyclization · Metal free ·
Synthetic Methods · Heterocycles
[
1] a) J. Cossy, Synthesis of Saturated Oxygenated Heterocycles I: 5- and 6-
Membered Rings; Springer: Paris, 2014; b) J. Cossy, Synthesis of
Saturated Oxygenated Heterocycles II: 7-to 16-Membered Rings; Spring-
er: Paris, 2014; c) W.-D. Meng, F.-L. Qing, Curr. Top. Med. Chem. 2006, 6,
Experimental Section
General procedure for the synthesis of saturated oxygen rings: In
1
499; d) E. Vitaku, D. T. Smith, J. T. Njardarson, J. Med. Chem. 2014, 57,
10257; e) Q. Lu, D. S. Harmalkar, Y. Choi, K. Lee, Molecules 2019, 24,
3778; f) D. C. Blakemore, L. Castro, I. Churcher, D. C. Rees, A. W. Thomas,
D. M. Wilson, A. Wood, Nat. Chem. 2018, 10, 383; g) M. E. Welsch, S. A.
Snyder, B. R. Stockwell, Curr. Opin. Chem. Biol. 2010, 14, 347; h) R. D.
Taylor, M. MacCoss, A. D. G. Lawson, J. Med. Chem. 2014, 57, 5845;
i) T. Y. Zhang, Adv. Heterocycl. Chem. 2017, 121, 1; j) A. Lorente, J.
Lamariano-Merketegi, F. Albericio, M. Álvarez, Chem. Rev. 2013, 113,
4567; k) C. Molinaro, E. M. Phillips, B. Xiang, E. Milczek, M. Shevlin, J.
Balsells, S. Ceglia, J. Chen, L. Chen, Q. Chen, Z. Fei, S. Hoerrner, J. Qi, M.
de Lera Ruiz, L. Tan, B. Wan, J. Yin, J. Org. Chem. 2019, 84, 8006.
a 15 mL plastic tube (PVC), a solution of 1, PIDA (0.30 mmol,
1
.5 equiv) in anhyd DCM (0.1 M) stirred for 5 min at 0°C. Py·HF
(0.40 mmol, 2.0 equiv) was added to the mixture. After 1 min the
mixture was quenched with sat. aq NaHCO solution and extracted
3
with DCM (3×20 mL). Then combined organic layers dried over
Na SO4 and filtered, evacuated under vacuum. The residue was
2
purified by triethylamine-treated (Et N/PE=1:100) silica gel column
3
chromatography (PE) to give saturated oxygen ring compounds 2.
[
2] a) N. K. Devaraj, ACS Cent. Sci. 2018, 4, 952; b) L. Li, Z. Zhang, Molecules
General procedure for the synthesis of saturated nitrogen rings:
In a 15 mL plastic tube (PVC), a solution of vinyl azide amine 5
2
016, 21, 1393; c) K. L. Kiick, E. Saxon, D. A. Tirrell, C. R. Bertozzi, Proc.
Natl. Acad. Sci. USA 2002, 99, 19; d) X. Zhang, Y. Zhang, Molecules 2013,
18, 7145; e) N. J. Agard, J. M. Baskin, J. A. Prescher, A. Lo, C. R. Bertozzi,
ACS Chem. Biol. 2016, 10, 644.
(
0.20 mmol, 1.0 equivalent), PIDA (0.30 mmol, 1.5 equiv) in anhy-
drous DCM (0.1 M) Stir at 25°C for 5 minutes. Py·HF (0.40 mmol,
[
3] a) S. Melkko, Y. Zhang, C. E. Dumelin, J. Scheuermann, D. Neri, Angew.
Chem. 2007, 119, 4755; Angew. Chem. Int. Ed. 2007, 46, 4671; b) N. U. A.
Mohsin, M. Ahmed, M. Irfan, J. Chil. Chem. Soc. 2019, 64, 4523; c) X. Dai,
W. Liu, Q. Zhou, C. Cheng, C. Yang, S. Wang, M. Zhang, P. Tang, H. Song,
D. Zhang, Y. Qin, J. Org. Chem. 2016, 81, 162.
2
.0 equiv) was added to the mixture. After 1 minute, the mixture
was quenched with saturated NaHCO3. It was washed with aqueous
NaHCO3 solution and extracted with DCM (3×20 mL). The com-
bined organic layers were then dried over Na SO and filtered, and
2
4
evacuated under vacuum. The residue was purified by basic
alumina column chromatography (PE/EA=20:1) to give saturated
nitrogen ring compounds 6.
[4] a) M. Zheng, S. Hwang, T. Snyder, J. Aquilina, G. Proni, M. M. Paz, P.
Pradhan, S.-Y. Cheng, E. Champeil, Bioorg. Chem. 2019, 92, 103280;
b) M. A. Aga, S. Rayees, A. Rouf, B. Kumar, A. Sharma, P. V. V. S. Nagaraju,
G. Singh, S. C. Taneja, Bioorg. Med. Chem. 2017, 25, 1440; c) C. Held, H.
Hübner, R. Kling, Y. A. Nagel, H. Wennemers, P. Gmeiner, ChemMedChem
2013, 8, 772; d) H.-Q. Liu, C.-C. Song, Y.-H. Niu, T. Li, Q. Li, X. S. Ye, Org.
Biomol. Chem. 2017, 15, 5912.
4-azido-4-fluoro-2,2-diphenyltetrahydrofuran (2d). Colorless oil;
1H NMR (600 MHz, CDCl3) δ 7.42–7.37 (m, 4H), 7.32 (dt, J=12.0,
Chem Asian J. 2020, 15, 1–6
www.chemasianj.org
4
© 2020 Wiley-VCH GmbH
��
These are not the final page numbers!

Communication
[
[
5] S. Yang, S. Zhu, D. Lu, Y. Gong, Org. Lett. 2019, 21, 8464.
6] Z. Fei, X. Xiong, C. Cheung, W. Liu, Q. Shen, J. Zhang, H. Gao, J. Bian,
Synlett 2019, 30, 1228.
2017, 19, 6240; f) J. Tang, P. Sivaguru, Y. Ning, G. Zanoni, X. Bi, Org. Lett.
2017, 19, 4026; g) Y. Ning, Q. Ji, P. Liao, E. A. Anderson, X. Bi, Angew.
Chem. 2017, 129, 13993; Angew. Chem. Int. Ed. 2017, 56, 13805; h) L.
Zhang, G. Sun, X. Bi, Chem. Asian J. 2016, 11, 3018; i) Z. Zhang, R. K.
Kumar, G. Li, D. Wu, X. Bi, Org. Lett. 2015, 17, 6190; j) Z. Liu, J. Liu, L.
Zhang, P. Liao, J. Song, X. Bi, Angew. Chem. 2014, 126, 5409; Angew.
Chem. Int. Ed. 2014, 53, 5305; k) Z. Liu, P. Liao, X. Bi, Org. Lett. 2014, 16,
3668; l) L. Li, S. Cao, F. Lin, P. Liao, Y. Ning, Eur. J. Org. Chem. 2020, 6,
693.
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
[7] For recent reviews, see: a) J. Fu, G. Zanoni, E. A. Anderson, X. Bi, Chem.
Soc. Rev. 2017, 46, 7208; b) H. Hayashi, A. Kaga, S. Chiba, J. Org. Chem.
2
017, 82, 11981; c) B. Hu, S. G. DiMagno, Org. Biomol. Chem. 2015, 13,
3844; d) N. Jung, S. Bräse, Angew. Chem. 2012, 124, 12335; Angew.
Chem. Int. Ed. 2012, 51, 12169.
[
8] E. López, L. A. López, Angew. Chem. 2017, 129, 5203; Angew. Chem. Int.
Ed. 2017, 56, 5121.
[12] For recent reviews, see: a) W. K. Hagmann, J. Med. Chem. 2008, 51, 4359;
b) E. P. Gillis, K. J. Eastman, M. D. Hill, D. J. Donnelly, N. A. Meanwell, J.
Med. Chem. 2015, 58, 8315; c) N. A. Meanwell, J. Med. Chem. 2011, 54,
2529; d) J. Wang, M. Sánchez-Roselló, J. L. Aceña, C. del Pozo, A. E.
Sorochinsky, S. Fustero, V. A. Soloshonok, H. Liu, Chem. Rev. 2014, 114,
2432; e) S. Purser, P. R. Moore, S. Swallow, V. Gouverneur, Chem. Soc.
Rev. 2008, 37, 320; f) C. Isanbor, D. O’Hagan, J. Fluorine Chem. 2006, 127,
303.
[9] N. Thirupathi, F. Wei, C.-H. Tung, Z. Xu, Nat. Commun. 2019, 10, 3158.
10] a) J. R. Wolstenhulme, V. Gouverneur, Acc. Chem. Res. 2014, 47, 3560;
b) S. R. Chemler, M. T. Bovino, ACS Catal. 2013, 3, 1076; c) T. Wu, G. Yin,
G. Liu, J. Am. Chem. Soc. 2009, 131, 16354; d) S. C. Wilkinson, O. Lozano,
M. Schuler, M. C. Pacheco, R. Salmon, V. Gouverneur, Angew. Chem.
[
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
2
009, 121, 7217; Angew. Chem. Int. Ed. 2009, 48, 7083; e) W. Yuan, K. J.
Szabó, Angew. Chem. 2015, 127, 8653; Angew. Chem. Int. Ed. 2015, 54,
533; f) D. Parmar, M. Rueping, Chem. Commun. 2014, 50, 13928; g) S.
8
[13] W.-X. Lv, Q. Li, J. -Li Li, Z. Li, E. Lin, D.-H. Tan, Y.-H. Cai, W.-X. Fan, H.
Wang, Angew. Chem. 2018, 130, 16782; Angew. Chem. Int. Ed. 2018, 57,
16544.
Suzuki, T. Kamo, K. Fukushi, T. Hiramatsu, E. Tokunaga, T. Dohi, Y. Kita,
N. Shibata, Chem. Sci. 2014, 5, 2754; h) T. Xu, S. Qiu, G. Liu, Chin. J.
Chem. 2011, 29, 2785; i) L. E. Combettes, O. Lozano, V. Gouverneur, J.
Fluorine Chem. 2012, 143, 167; j) T. Kitamura, A. Miyake, K. Muta, J.
Oyamada, J. Org. Chem. 2017, 82, 11721; k) Q. Wang, W. Zhong, X. Wei,
M. Ning, X. Meng, Z. Li, Org. Biomol. Chem. 2012, 10, 8566; l) J. Cui, Q.
Jia, R.-Z. Feng, S.-S. Liu, T. He, C. Zhang, Org. Lett. 2014, 16, 1442; m) H.-
T. Huang, T. C. Lacy, B. Błachut, G. X. Ortiz Jr, Q. Wang, Org. Lett. 2013,
15, 1818; n) S. Arimitsu, M. Nakasone, E. Gima, Tetrahedron Lett. 2018,
[14] X. Sun, X. Li, S. Song, Y. Zhu, Y.-F. Liang, N. Jiao, J. Am. Chem. Soc. 2015,
137, 6059.
[15] F. Shi, J. P. Waldo, Y. Chen, R. C. Larock, Org. Lett. 2008, 10, 2409.
[16] P. Shanmugavelan, S. Nagarajan, M. Sathishkumar, A. Ponnuswamy, P.
Yogeeswari, D. Sriram, Bioorg. Med. Chem. Lett. 2011, 21, 7273.
[17] K. Kuroda, Y. Hayashi, T. Mukaiyam, Tetrahedron 2007, 63 6358.
[18] a) B. Zhou, M. K. Haj, E. N. Jacobsen, K. N. Houk, X.-S. Xue, J. Am. Chem.
Soc. 2018, 140, 15206; b) S. Shu, Y. Li, J. Jiang, Z. Ke, Y. Liu, J. Org. Chem.
2019, 84, 458.
59, 887; o) L. F. Lourie, Y. A. Serguchev, M. V. Ponomarenko, E. B.
Rusanov, M. V. Vovk, N. V. Ignaťev, Tetrahedron 2013, 69, 833; p) K. M.
Mennie, S. M. Banik, E. C. Reichert, E. N. Jacobsen, J. Am. Chem. Soc.
2018, 140, 4797.
[
11] a) Y. Ning, P. Sivaguru, G. Zanoni, E. A. Anderson, X. Bi, Chem. 2020, 6,
486; b) H. Li, B. R. P. Reddy, X. Bi, Org. Lett. 2019, 21, 9358; c) Y. Ning, A.
Mekareeya, K. R. Babu, E. A. Anderson, X. Bi, ACS Catal. 2019, 9, 4203;
d) B. Liu, Y. Ning, M. Virelli, G. Zanoni, E. A. Anderson, X. Bi, J. Am. Chem.
Soc. 2019, 141, 1593; e) Y. Ning, X.-F. Zhao, Y.-B. Wu, X. Bi, Org. Lett.
Manuscript received: October 6, 2020
Revised manuscript received: October 22, 2020
Version of record online: ■■■, ■■■■
Chem Asian J. 2020, 15, 1–6
www.chemasianj.org
5
© 2020 Wiley-VCH GmbH
��
These are not the final page numbers!

Communication
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
COMMUNICATION
D. Bai, L. Li, X. Li, Y. Lu, Y. Wu*, B. Ra-
jendra Prasad Redd, Y. Ning*
1
– 6
Fluorocyclization of Vinyl Azides
for the Formation of 3-Azido Het-
erocycles
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
Synthetic Methods. A novel strategy
for the synthesis of 3-azido saturated
heterocycles via the fluorocyclization
of vinyl azides has been developed.
This method furnishes a broad range
of 3-azido oxa/azaheterocycles that
are typically difficult to attain with
post functionalization.