Indium-mediated annulation of 2-azidoaryl aldehydes with propargyl bromides to [1,2,3]triazolo[1,5-a]quinolines

Article abstract of DOI:10.1039/d1ob01183a

An efficient indium-mediated cascade annulation reaction of 2-azidoaryl aldehydes with propargyl bromides is reported. The aromatic 5/6/6-fused heterocycles, [1,2,3]triazolo[1,5-a]quinoline derivatives, could be constructed in one pot in moderate yields with a broad substrate scope. Mechanistic studies indicated that the reaction proceeded through allenol formation, azide-allene [3 + 2] cycloaddition, and dehydration. The synthetic potential of the products including the denitrogenative functionalization and the Pd-catalyzed coupling reactions has also been explored.

Full text of DOI:10.1039/d1ob01183a

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PAPER
Indium-mediated annulation of 2-azidoaryl
aldehydes with propargyl bromides to [1,2,3]
triazolo[1,5-a]quinolines†
Cite this: Org. Biomol. Chem., 2021,
19, 6346
Xiaomin Zhang,‡a Jiali Yang,‡a Ni Xiong,a Zhe Han,b Xinhua Duan a and
a,c
Rong Zeng
*
An efficient indium-mediated cascade annulation reaction of 2-azidoaryl aldehydes with propargyl bro-
mides is reported. The aromatic 5/6/6-fused heterocycles, [1,2,3]triazolo[1,5-a]quinoline derivatives,
could be constructed in one pot in moderate yields with a broad substrate scope. Mechanistic studies
indicated that the reaction proceeded through allenol formation, azide–allene [3 + 2] cycloaddition, and
dehydration. The synthetic potential of the products including the denitrogenative functionalization and
the Pd-catalyzed coupling reactions has also been explored.
Received 19th June 2021,
Accepted 30th June 2021
DOI: 10.1039/d1ob01183a
rsc.li/obc
Typically, [1,2,3]triazolo[1,5-a]quinolines can be divided
into a, b, and c rings, and efforts have been made to construct
Introduction
[1,2,3]Triazolo[1,5-a]quinoline is an important aromatic het- these rings by developing efficient methods. While the tran-
erocycle with a 5/6/6-fused ring system. The existing core skel- sition metal-catalyzed coupling reactions of 1-phenyl-1H-1,2,3-
eton, which contains both the [1,2,3]triazolo[1,5-a]pyridine1 triazole derivatives provided general approaches for building
and quinoline scaffolds,2 is an essential building block and is the middle b ring (path a, Scheme 1),5 the c ring could be con-
extremely attractive for materials science and pharmaceutical structed by the oxidative N–N bond formation of (quinolin-2-
chemistry (Fig. 1).3 For example, while Diquat was able to yl)methylene hydrazine derivatives directly under oxidative
interact with DNA,3a the 3-hydroxy-2-[4-(trifluoromethyl) conditions (path b).6 In 2017, the Nachtsheim group reported
phenyl][1,2,3]triazolo[1,5-a]quinolinium inner salt AZ1 was the one-pot construction of the b and c rings of [1,2,3]triazolo
found to be a new aryl hydrocarbon receptor (AhR) agonist [1,5-a]quinolines through tandem Sandmeyer azide formation
with exceptional potency.3e Moreover, the ring-chain isomeri- and subsequent intramolecular azide–alkyne cycloaddition of
zation of the cyclic triazole framework of [1,2,3]triazolo[1,5-a] enynes, while the complex starting materials were prepared
quinolines offers new tools for the construction of functiona- using iridium catalysis via C–H functionalization (path c).7
lized quinoline derivatives via efficient denitrogenative ring- Alternatively, the annulation reaction of 2-azidoaryl aldehyde/
opening, providing potential in synthetic chemistry.4 The nitrile/ester with 1,3-dicarbonyl compounds offered an
development of new, efficient, and general synthetic methods efficient tool for building the b and c rings of [1,2,3]triazolo
for the preparation of [1,2,3]triazolo[1,5-a]quinolines is [1,5-a]quinolines in a single step by using a strong base, typi-
required and has drawn significant attention from chemists.
cally DBU, t-BuOK, and NaH (path d).8a–8d Given that low-
valent metals can mediate the allenylation reaction of propar-
gyl bromides and aldehydes,9,10 we proposed that the reaction
of 2-azidoaryl aldehydes with propargyl bromides would
proceed through metal-mediated allenylation of propargyl bro-
aSchool of Chemistry, MOE Key Laboratory for Nonequilibrium Synthesis and
Modulation of Condensed Matter, Xi’an Key Laboratory of Sustainable Energy
Materials Chemistry, Xi’an Jiaotong University (XJTU), Xi’an 710049, P. R. China.
E-mail: rongzeng@xjtu.edu.cn
bSchool of Nuclear Science and Technology, Xi’an Jiaotong University (XJTU),
Xi’an 710049, P. R. China
cGuangdong Provincial Key Laboratory of Catalysis, Southern University of Science
and Technology, Shenzhen, 518055 Guangdong, P. R. China
†Electronic supplementary information (ESI) available. CCDC 2078447. For ESI
and crystallographic data in CIF or other electronic format see DOI: 10.1039/
d1ob01183a
Fig. 1 Bioactive molecules with the [1,2,3]triazolo[1,5-a]quinoline
‡These authors contributed equally.
moiety.
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Table 1 Optimization of the reaction conditionsa
Entry
Metal
Solvent
Temperature
Yieldb (%)
1
2
3
4
5
6
7
8
In
Mn
Zn
Fe
In
In
In
In
In
In
In
In
In
In
In
In
DME
DME
DME
DME
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
71 (68)c
0
0
9
THF
66
53
32
25
33
69
32
52
15
50
58
36
MTBE
1,4-Dioxane
DCE
DCM
DMA
DMSO
DMF
MeCN
MeOH
DME
9
Scheme 1 Strategies for the synthesis of [1,2,3]triazole[1,5-a]quinolines.
10
11
12
13
14
15
16
mides,11 [3 + 2] azide–allene cycloaddition,12 and subsequent
dehydration to afford the [1,2,3]triazolo[1,5-a]quinoline deriva-
tives. Herein, we report such a tandem one-pot reaction of
2-azidoaryl aldehydes with propargyl bromides. This reaction
could be mediated by indium powder and the reductive con-
dition was mild, providing a reliable and novel strategy for the
synthesis of [1,2,3]triazolo[1,5-a]quinolines.
60 °C
100 °C
DME
a The reactions were conducted with 1a (0.2 mmol), 2a (0.26 mmol),
metal (0.3 mmol), and LiI (0.4 mmol) under N2 for 24 h. b All yields are
based on isolation. c The yield in parentheses is based on isolation of
the reaction product at the 0.5 mmol scale.
Table 2 Scope of propargyl bromidesa,b
Results and discussion
To verify the feasibility of the design, the reaction of 2-azido-
benzaldehyde (1a) and 1-bromohept-2-yne (2a) was first con-
ducted in the presence of 1.5 equiv. of indium and 2.0 equiv.
of LiI in DME at room temperature (rt) under a N2 atmosphere.
The reaction proceeded smoothly and the desired product 3aa
was obtained in 71% yield based on isolation (entry 1). The
reaction conditions were then optimized (Table 1). First, the
indium powder was proven to be important for the transform-
ation.11 Other related metals, such as Mn and Zn, did not
promote the reaction, while Fe powder only led to a low yield
(entries 2–4). The solvent effect was also surveyed. Other ether
solvents, such as THF, MTBE, and 1,4-dioxane, gave relatively
lower yields (66%, 53%, and 32%, respectively) (entries 5–7),
while chlorinated solvents, such as DCE and DCM, afforded
the desired products in only 25–33% yields (entries 8 and 9).
The reaction in DMA gave a result similar to that with DME
(entry 10). Other polar solvents, such as DMSO, DMF, and
MeCN, afforded the product only in 15–52% yields (entries
11–13). Interestingly, the reaction could be conducted in a
protic solvent (MeOH) with a lower yield (entry 14). Moreover,
when the reaction temperature was increased to 60 or 100 °C,
the yields decreased significantly (entries 15 and 16).
a The reactions were conducted with 1a (0.5 mmol), 2 (0.65 mmol), In
(0.75 mmol), and LiI (1.0 mmol) in DME (5 mL) at room temperature
under N2 for 24 h. b All yields are based on isolation. c The reaction
temperature was 60 °C.
With the optimized conditions in hand, the scope of the
reaction was first tested using various propargyl bromides
(Table 2). 3-Alkyl, alkenyl, or aryl substituted propargyl bro-
mides were tolerated under the standard reaction conditions groups, such as t-Bu (3ae) and OMe (3af), or electron-with-
and the corresponding 4-substituted [1,2,3]triazolo[1,5-a]qui- drawing groups, such as CF3 (3ag) and COOMe (3ah), on the
nolines were obtained in moderate yields. Electron-donating phenyl group were tolerated well and the products were iso-
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Table 3 Scope of 2-azidoaryl aldehydesa,b
lated in 40–60% yields. While the electron-donating or elec-
tron-withdrawing groups did not affect the reaction signifi-
cantly, the variation in the yield of these transformations is
probably dependent on the stability of substrate 2 under these
conditions. The reaction of 1a with 3-(2-naphthyl)-propargyl
bromide occurred smoothly and provided the corresponding
product in 68% yield (3aj). Intriguingly, when propargyl bro-
mides containing heteroaryl groups, such as thiophen-2-yl and
quinolin-6-yl groups, were treated with 1a, the corresponding
cyclization products were obtained successfully with only
slightly lower yields (3ak and 3al). While the ether group was
tolerated in the reaction (3an and 3ao), the simple propargyl
bromide afforded the corresponding product 3ap in only 22%
yield. The structure of 3ab was further confirmed by single
crystal X-ray diffraction (Fig. 2).13
The scope of the functionalized 2-azidoaryl aldehydes 1 was
next investigated with 2a under the standard reaction con-
ditions (Table 3). When substrates 1 bearing a methyl group
were used, the reaction proceeded well to afford the corres-
ponding product (3ba). The highly strained cyclopropane ring
was unreactive under the standard conditions and remained
intact during the transformation (3ca). The carbon–halogen
bonds (3da and 3ea) were also tolerated well although a higher
reaction temperature (60 °C) was required to facilitate higher
yields. All the reactions proceeded smoothly to afford the
corresponding products when substituted phenyl groups with
either an electron-donating group, such as OMe (3ga), or an
electron-withdrawing group, such as CF3 (3ha) or CN (3ia),
were used. Moreover, heteroaryl groups, such as pyridin-2-yl
(3ja), furan-2-yl (3ka), or thiophen-2-yl (3la), were also toler-
ated. While the simple ester groups were able to remain (3ma
and 3na), interestingly, substrates bearing complex scaffolds,
such as (L)-menthol, dehydroepiandrosterone, and cholesterol
derivatives, also gave moderate yields (3oa, 3pa, and 3qa).
Notably, when 1-(2-azidophenyl)propan-1-one 1r was prepared
and subjected to the reaction with 2a under the standard con-
ditions, the desired product 3ra was not detected but only the
reduction product of the starting material was obtained.
a The reactions were conducted with 1 (0.5 mmol), 2a (0.65 mmol), In
(0.75 mmol), and LiI (1.0 mmol) in DME at room temperature under
N2 for 24 h. b All yields are based on isolation. c The reaction tempera-
ture was 60 °C. d 1-Bromo-2-butyne 2b was used. e 1-(2-Azidophenyl)
propan-1-one was used.
ð3Þ
For understanding the reaction process, a series of experi-
ments were conducted. First, while the reaction of azidoben-
zene 1s with 2a under the standard conditions failed to afford
the triazole product (eqn (1)), the reaction of 2-nitrobenzalde-
hyde 1t with 2a produced allenol 4a in 52% yield (eqn (2)).
These results indicated that the reaction between aldehyde
and propargyl bromide at the beginning is crucial for the
transformation. Second, when 2-aminophenyl allenol 4b was
prepared and subjected to the Sandmeyer azidation, the
desired product 2-azidophenyl allenol 4c was not isolated but
only the cyclization product 3aa was obtained in 20% yield
(eqn (3)), indicating that the azide–allene cycloaddition and
the subsequent dehydration are highly driven to produce the
[1,2,3]triazolo[1,5-a]quinoline product even in the absence of
indium.
ð1Þ
ð2Þ
Based on the mechanistic studies, a plausible mechanism
was proposed (Scheme 2). First, the reaction of propargyl
bromide 2a in the presence of indium formed intermediate
Int 1, which underwent 1,2-addition with 2-azidobenzaldehyde
1a to afford allenol 4c. The fast intramolecular azide–allene
Fig. 2 The crystal structure of compound 3ab. Atoms are presented as
thermal ellipsoids at 50% probability level.
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smoothly to afford the alkenylation product 7b in 49% yield
(route d).14c The Sonogashira coupling reaction of substrate
3ea with phenylacetylene proceeded smoothly to generate the
internal alkyne 7c in 59% yield (route e).14d Substrate 3ea
underwent the Suzuki coupling reaction with phenylboronic
acid in the presence of Pd(OAc)2 and LBphos to produce the
corresponding product 7d in a moderate yield (route f).14e–14g
Scheme 2 Plausible mechanism.
Conclusions
In summary, we have developed a one-pot synthesis of [1,2,3]
triazolo[1,5-a]quinolines by an annulation reaction of 2-azi-
doaryl aldehydes and propargyl bromides in moderate yields.
A stoichiometric amount of indium powder promoted the
transformation, which was proposed to proceed by a tandem
procedure involving allenol formation, azide–allene [3 + 2]
cycloaddition, and subsequent dehydration. The reaction
scope was broad when functional groups, such as esters,
alkenes, and ethers, were well tolerated. In addition, the syn-
thetic potential, including Suzuki coupling, Sonogashira coup-
ling, directed C–H arylation, and the denitrogenative ring-
opening of the corresponding products, was studied.
[3 + 2] cycloaddition and subsequent dehydration led to the
final product 3aa.
Finally, the synthetic potential of the prepared [1,2,3]tria-
zolo[1,5-a]quinoline was examined (Scheme 3). First, the
product 3aa served as the quinolin-2-yl carbene precursor to
react with an excess amount of HOAc or 3.0 equiv. of
TsOH·H2O under reflux for 8 hours to afford (quinolin-2-yl)
methyl acetate 5a or (quinolin-2-yl)methyl 4-methyl-
benzenesulfonate 5b (route a).14a The Brønsted acid-promoted
dinitrogen liberation of the triazole moiety was followed by
addition of acetic acid or TsOH·H2O, leading to the final
product in 93% or 94% yield, respectively. In addition, the
[5 − 2 + 2] cycloaddition product substrate 6 was obtained by
treating product 3aa with 3-methylbenzonitrile in the presence
of 25 mol% of BF3·Et2O in DCB and DCE at 140 °C for
12 hours (route b). The denitrogenation provided the strong
driving force for the transformation.6c The C–H arylation
product 7a was obtained by treating 3aa with iodobenzene in
the presence of 10 mol% of Pd(OAc)2 and 2 equiv. of Ag2CO3
under air for 17 hours (route c).14b Moreover, the coupling
reaction of compound 3ea with 4-methyl-N’-(1-(p-tolyl)ethyli-
dene)benzenesulfonohydrazide in the presence of 1 mol% of
Pd(OAc)2, 2 mol% of dppp, and 4 equiv. of t-BuOLi occurred
Conflicts of interest
The authors declare no competing financial interest.
Acknowledgements
R.Z. is grateful for the financial support from the National
Natural Science Foundation of China (21901197), the Natural
Science Basic Research Plan in Shaanxi Province of China
(2019JM093), the Guangdong Provincial Key Laboratory of
Catalysis (2020B121201002), and the start-up funds from Xi’an
Jiaotong University (XJTU). We thank the Instrument Analysis
Center of XJTU for assistance with HRMS analysis.
Notes and references
1 For selected reviews on [1,2,3]triazolo[1,5-a]pyridines, see:
(a) B. Abarca, R. Ballesteros and M. Elmasnouy,
Triazolopyridines
20.
Hydrogenation
Reactions#,
Tetrahedron, 1999, 55, 12881–12884; (b) G. Jones, The
Chemistry of the Triazolopyridines: an Update, Adv.
Heterocycl. Chem., 2002, 83, 1–70; (c) G. Jones and
B. Abarca, The Chemistry of the [1,2,3]Triazolo[1,5-a]pyri-
dines: an Update, Adv. Heterocycl. Chem., 2010, 100, 195–
252.
2 For selected reviews on quinolines, see: (a) R. H. Manske,
The Chemistry of Quinolines, Chem. Rev., 1942, 30,
113–144; (b) J. P. Michael, Quinoline, Quinazoline and
Acridone Alkaloids, Nat. Prod. Rep., 2000, 17, 603–620;
(c) S. M. Prajapati, K. D. Patel, R. H. Vekariya, S. N. Panchal
Scheme 3 Synthetic potential of [1,2,3]triazole[1,5-a]quinolines.
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and H. D. Patel, Recent Advances in the Synthesis of
Organic & Biomolecular Chemistry
(II)-Catalyzed Denitrogenative Reaction of N-Sulfonyl-1,2,3-
triazoles with Isatins for the Construction of Indigoids,
Org. Lett., 2017, 19, 5764–5767.
Quinolines: A review, RSC Adv., 2014, 4, 24463–24476;
(d) T. Iwai and M. Sawamura, Transition-Metal-Catalyzed
Site-Selective C–H Functionalization of Quinolines beyond
C2 Selectivity, ACS Catal., 2015, 5, 5031–5040;
(e) A. K. Dhiya, A. Monga and A. Sharma, Visible-Light-
Mediated Synthesis of Quinolines, Org. Chem. Front., 2021,
8, 1657–1676.
5 (a) Z. Liu, D. Zhu, B. Luo, N. Zhang, Q. Liu, Y. Hu, R. Pi,
P. Huang and S. Wen, Mild Cu(I)-catalyzed Cascade
Reaction of Cyclic Diaryliodoniums, Sodium azide, and
Alkynes: Efficient Synthesis of Triazolophenanthridines,
Org. Lett., 2014, 16, 5600–5603; (b) H. Qiu, P. Zhou, W. Liu,
J. Zhang and B. Chen, Palladium–Catalyzed Intermolecular
Carbopalladation Cascade: Facile Synthesis of [1,2,3]
Triazolo[1,5−a]quinolines from o–Triazole Bromobenzenes
and Internal Alkynes, ChemistrySelect, 2020, 5, 2935–2939;
(c) J. Yang, S. Xiong, Y. Ren, T. Xiao and Y. Jiang, Copper-
catalyzed Cross-coupling and Sequential Allene-Mediated
Cyclization for the Synthesis of 1,2,3-triazolo[1,5-a]quino-
lines, Org. Biomol. Chem., 2020, 18, 7174–7182;For related
papers, see: (d) Y.-Y. Hu, J. Hu, X.-C. Wang, L.-N. Guo,
X.-Z. Shu, Y.-N. Niu and Y.-M. Liang, Copper-Catalyzed
Tandem Synthesis of [1,2,3]Triazolo[5,1-a]isoquinolines
3 (a) P. J. Llabres-Campaner, L. Guijarro, C. Giarratano,
R. Ballesteros-Garrido, R. J. Zaragoza, M. J. Aurell,
E. Garcia-Espana, R. Ballesteros and B. Abarca, Synthesis,
Optical Properties, and DNA Interaction of New Diquats
Based on Triazolopyridines and Triazoloquinolines, Chem.
– Eur. J., 2017, 23, 12825–12832; (b) Q. Hu, L. Yin, A. Ali,
A. J. Cooke, J. Bennett, P. Ratcliffe, M. M. Lo, E. Metzger,
S. Hoyt and R. W. Hartmann, Novel Pyridyl Substituted 4,5-
Dihydro-[1,2,4]triazolo[4,3-a]quinolines as Potent and
Selective Aldosterone Synthase Inhibitors with Improved in
Vitro Metabolic Stability, J. Med. Chem., 2015, 58, 2530–
2537; (c) F. A. Bassyouni, S. M. Abu-Baker, K. Mahmoud,
M. Moharam, S. S. El-Nakkady and M. A. Rehim, Synthesis
and Biological Evaluation of Some New Triazolo[1,5-a]qui-
noline Derivatives as Anticancer and Antimicrobial Agents,
RSC Adv., 2014, 4, 24131–24141; (d) S. Pankajakshan,
Z. G. Chng, R. Ganguly and T. P. Loh, Copper-Catalyzed
Aerobic Carboxygenation and N-arylation of [1,2,3]Triazolo
[1,5-a]pyridines towards Pyridinium Triazolinone Ylides,
Chem. Commun., 2015, 51, 5929–5231; (e) J. W. Richard,
R. B. David, B. Rana, F. Alwyn, R. Martin, J. C. Rowlands
and I. R. Mellor, Fused Mesoionic Heterocyclic Compound
Are a New Class of Aryl Hydrocarbon Receptor (AhR)
Agonist of Exceptional Potency, Toxicology, 2012, 302, 140–
145.
and
Their
Transformation
to
1,3-Disubstituted
Isoquinolines, Tetrahedron, 2010, 66, 80–86; (e) A. Kumar,
S. S. Shinde, D. K. Tiwari, B. Sridhar and P. R. Likhar,
Palladium Catalyzed Domino Reaction of 1,4-Disubstituted
1,2,3-Triazoles via Double C–H Functionalization: One-pot
Synthesis of Triazolo[1,5-f]phenanthridines, RSC Adv.,
2016, 6, 43638–43647; (f) Z. Wang, B. Li, X. Zhang and
X. Fan, One-Pot Cascade Reactions Leading to Pyrido[2′,1′:
2,3]imidazo[4,5-c,][1,2,3]triazolo[1,5-a]quinolines
under
Bimetallic Relay Catalysis with Air as the Oxidant, J. Org.
Chem., 2016, 81, 6357–6363; (g) J. Wang, J. Yang, X. Fu,
G. Qin, T. Xiao and Y. Jiang, Synthesis of Triazole-Fused
Phenanthridines through Pd-Catalyzed Intramolecular
Phenyl C–H Activation of 1,5-Diaryl-1,2,3-triazoles, Synlett,
2019, 1452–1456; (h) P. A. Abbott, R. V. Bonnert,
M. V. Caffrey, P. A. Cage, A. J. Cooke, D. K. Donald,
M. Furber, S. Hill and J. Withnall, Fused Mesoionic
Heterocycles: Synthesis of [1,2,3]Triazolo[1,5-a]quinoline,
[1,2,3]Triazolo[1,5-a]quinazoline, [1,2,3]Triazolo[1,5-a]qui-
noxaline and [1,2,3]Triazolo[5,1-c]benzotriazine Derivatives,
Tetrahedron, 2002, 58, 3185–3198.
6 (a) J. H. Boyer, R. Borgers and L. T. Wolford, The
Azomethine Linkage of Pyridine in Ring-Closure
Isomerizations, J. Am. Chem. Soc., 1957, 79, 678–680;
(b) R. A. Abramovitch and T. Takaya, Reaction of Sulfonyl
Azides with Pyridines and Fused Pyridine Derivatives,
J. Org. Chem., 1972, 37(12), 2022–2029; (c) Y.-M. Cai,
X. Zhang, C. An, Y.-F. Yang, W. Liu, W.-X. Gao, X.-B. Huang,
Y.-B. Zhou, M.-C. Liu and H.-Y. Wu, Catalyst-free Oxidative
N–N Coupling for the Synthesis of 1,2,3-Triazole
Compounds with tBuONO, Org. Chem. Front., 2019, 6,
1481–1484; (d) Z.-H. Shang, Z.-X. Zhang, W.-Z. Weng,
Y.-F. Wang, T.-W. Cheng, Q.-Y. Zhang, L.-Q. Song,
T.-Q. Shao, K.-X. Liu and Y.-P. Zhu, A Metal– and Azide–free
Oxidative Coupling Reaction for the Synthesis of [1,2,3]
Triazolo[1,5−a]quinolines and Their Application to
Construct C−C and C−P Bonds, 2−Cyclopropylquinolines
4 For selected reviews on denitrogenative functionalization,
see: (a) D. Yadagiri, M. Rivas and V. Gevorgyan,
Denitrogenative Transformations of Pyridotriazoles and
Related
Compounds:
Synthesis
of
N-Containing
Heterocyclic Compounds and Beyond, J. Org. Chem., 2020,
85, 11030–11046; (b) N. V. Rostovskii, G. D. Titov and
I. P. Filippov, Recent Advances in Denitrogenative
Reactions of Pyridotriazoles, Synthesis, 2020, 3564–3576;
For selected papers on denitrogenative functionalization,
see: (c) A. N. Koronatov, K. K. Afanaseva, P. A. Sakharov,
N. V. Rostovskii, A. F. Khlebnikov and M. S. Novikov, Rh(II)-
Catalyzed Denitrogenative 1-Sulfonyl-1,2,3-triazole-1-alkyl-
1,2,3-triazole Cross-coupling as a Route to 3-Sulfonamido-
1H-pyrroles and 1,2,3-Triazol-3-ium Ylides, Org. Chem.
Front., 2021, 8, 1474–1481; (d) H. Khatua, S. K. Das, S. Roy
and B. Chattopadhyay, Dual Reactivity of 1,2,3,4-Tetrazole:
Manganese-Catalyzed Click Reaction and Denitrogenative
Annulation,
Angew.
Chem.,
2021,
60,
304–312;
(e) A. N. Koronatov, N. V. Rostovskii, A. F. Khlebnikov and
M. S. Novikov, Synthesis of 3-Alkoxy-4-pyrrolin-2-ones via
Rhodium(II)-Catalyzed Denitrogenative Transannulation of
1H-1,2,3-Triazoles with Diazo Esters, Org. Lett., 2020, 22,
7958–7963; (f) K. Pal, R. K. Shukla and C. M. R. Volla, Rh
6350 | Org. Biomol. Chem., 2021, 19, 6346–6352
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Paper
and Imidazo[1,5−a]quinolines, Adv. Synth. Catal., 2021,
363, 490–496; (e) T. Hirayama, S. Ueda, T. Okada,
N. Tsurue, K. Okuda and H. Nagasawa, Facile One-pot
Alkynes, Org. Lett., 2012, 14, 1346–1349; (i) J. Ye, W. Fan
and S. Ma, tert-Butyldimethylsilyl-directed Highly
Enantioselective Approach to Axially Chiral α-Allenols,
Chem. – Eur. J., 2013, 19, 716–720; ( j) J. Kuang and S. Ma,
One-Pot Synthesis of 1,3-Disubstituted Allenes from
1-Alkynes, Aldehydes, and Morpholine, J. Am. Chem. Soc.,
2010, 132, 1786–1787.
Synthesis
of
[1,2,3]Triazolo[1,5-a]pyridines
from
2-Acylpyridines by Copper(II)-Catalyzed Oxidative N−N
Bond Formation, Chem. – Eur. J., 2014, 20, 4156–4162;
(f) P. Xu and H. C. Xu, Electrochemical Synthesis of [1,2,3]
Triazolo[1,5−a]pyridines
through
Dehydrogenative 10 For selected papers on the metal-mediated synthesis of
Cyclization, ChemElectroChem, 2019, 6, 4177–4179;
(g) G. Jiang, Y. Lin, M. Cai and H. Zhao, Recyclable
Heterogeneous Copper(II)-Catalyzed Oxidative Cyclization
of 2-Pyridine Ketone Hydrazones towards [1,2,3]Triazolo
[1,5-a]pyridines, Synthesis, 2019, 4487–4497.
allenes from propargyl bromides and aldehydes, see:
(a) P. Place, C. Vernière and J. Goré, Synthése D’alcools
α-Alléniques
par
Réaction
D’organochromiques
Propargyliques Sur Les Aldéhydes Et Les Cétones,
Tetrahedron, 1981, 37, 1359–1367; (b) M. B. Isaac and
T. H. Chan, Indium-Mediated Coupling of Aldehydes with
Prop-2-ynyl Bromides in Aqueous Media, J. Chem. Soc.,
Chem. Commun., 1995, 1003–1004; (c) X.-H. Yi, Y. Meng and
C.-J. Li, Indium-Mediated Highly Diastereoselective
Allenylation in Aqueous Medium: Total Synthesis of
(+)-Goniofufurone, Chem. Commun., 1998, 449–450;
(d) A. Hoffmann-Röder and N. Krause, Enantioselective
Synthesis of and with Allenes, Angew, Chem., Int. Ed., 2002,
41, 2933–2935; (e) M.-J. Lin and T.-P. Loh, Indium-
Mediated Reaction of Trialkylsilyl Propargyl Bromide with
Aldehydes: Highly Regioselective Synthesis of Allenic and
Homopropargylic Alcohols, J. Am. Chem. Soc., 2003, 125,
13042–13043; (f) G. Xia and H. Yamamoto, Catalytic
Enantioselective Allenylation Reactions of Aldehydes with
Tethered Bis(8-quinolinolato) (TBOx) Chromium Complex,
J. Am. Chem. Soc., 2007, 129, 496–497; (g) C. Park and
P. H. Lee, Indium-Mediated Regio- and Chemoselective
Synthesis of α-Hydroxyalkyl Allenic Esters and Gold-
Catalyzed Cyclizations to Ethyl 2-Naphthoate Derivatives,
Org. Lett., 2008, 10, 3359–3362; (h) J. Park, S. H. Kim and
P. H. Lee, Selective Indium-Mediated 1,2,4-Pentatrien-3-
ylation of Carbonyl Compounds for the Efficient Synthesis
of Vinyl Allenols, Org. Lett., 2008, 10, 5067–5070.
7 L. D. Caspers, P. Finkbeiner and B. J. Nachtsheim, Direct
Electrophilic
C−H
Alkynylation
of
Unprotected
2-Vinylanilines, Chem. – Eur. J., 2017, 23, 2748–2752.
8 (a) G. P. Costa, M. F. Bach, M. C. Moraes, T. Barcellos,
E. J. Lenardão, M. S. Silva and D. Alves, Sequential
Organocatalytic Synthesis of [1,2,3]Triazolo[1,5−a]quino-
lines, Adv. Synth. Catal., 2020, 362, 5044–5055;
(b) T. C. Porter, R. K. Smalley, M. Teguiche and B. Purwono,
1,2,3-Triazolo[1,5-a]quinolines, -[1,7]naphthyridines, and
-benzo[1,5]diazepines by the Action of Diethyl 1,3-
Acetonedicarboxylate Anion on ortho-Substituted Aryl
Azides, Synthesis, 1990, 654–656; (c) C. Thomas,
R. K. Porter, M. S. Teguiche and B. Purwono, Tetrazolo[1,5-
a]quinolines and 1,2,3-Triazolo[1,5-a]quinazolines by the
Action of Cyanocarbanions on 2-Azidoarylcarbonyl
Compounds, Synthesis, 1997, 773–777; (d) N. T. Pokhodylo
and M. D. Obushak, A Convenient Synthesis of [1,2,3]
Triazolo[1,5-a]quinoline, Russ. J. Org. Chem., 2019, 55,
1241–1243.
9 For reviews on the synthesis and reactions of allenes, see:
(a) S. Ma, Some Typical Advances in the Synthetic
Applications of Allenes, Chem. Rev., 2005, 105, 2829–2871;
(b) S. Yu and S. Ma, Allenes in Catalytic Asymmetric
Synthesis and Natural Product Syntheses, Angew. Chem., 11 For reviews on alkyne–azide [3+2]cycloaddition, see:
Int. Ed., 2012, 51, 3074–3112; (c) X. Huang and S. Ma,
Allenation of Terminal Alkynes with Aldehydes and
Ketones, Acc. Chem. Res., 2019, 52, 1301–1312; (d) L. Liu,
R. M. Ward and J. M. Schomaker, Mechanistic Aspects and
Synthetic Applications of Radical Additions to Allenes,
Chem. Rev., 2019, 119, 12422–12490; (e) R. Blieck,
(a) H. C. Kolb, M. G. Finn and K. B. Sharpless, Click
Chemistry: Diverse Chemical Function from a Few Good
Reactions, Angew. Chem., Int. Ed., 2001, 40, 2004–2021;
(b) J. E. Hein and V. V. Fokin, Copper-Catalyzed Azide-
alkyne Cycloaddition (CuAAC) and Beyond: New Reactivity
of Copper(I) Acetylides, Chem. Soc. Rev., 2010, 39, 1302–
1315; (c) V. K. Tiwari, B. B. Mishra, K. B. Mishra, N. Mishra,
A. S. Singh and X. Chen, Cu-Catalyzed Click Reaction in
Carbohydrate Chemistry, Chem. Rev., 2016, 116, 3086–3240;
For selected papers, see: (d) V. V. Rostovtsev, L. G. Green,
V. V. Fokin and K. B. Sharpless, A Stepwise Huisgen
Cycloaddition Process: Copper(I)-Catalyzed regioselective
“Ligation” of Azides and Terminals Alkynes, Angew. Chem.,
Int. Ed., 2002, 41, 2596–2599; (e) R. P. Shirke and
S. S. V. Ramasastry, Organocatalytic β-Azidation of Enones
Initiated by an Electron-Donor-Acceptor Complex, Org.
Lett., 2017, 19, 5482–5485; (f) L.-Z. Yu, Y. Wei and M. Shi,
Copper-Catalyzed Cascade Cyclization of 1,5-Enynes via
Consecutive Trifluoromethylazidation/Diazidation and
M.
Taillefer
and
F.
Monnier,
Metal-Catalyzed
Intermolecular Hydrofunctionalization of Allenes: Easy
Access to Allylic Structures via the Selective Formation of
C−N, C−C, and C−O Bonds, Chem. Rev., 2020, 120, 13545–
13598; (f) N. Krause and A. S. K. Hashmi, Modern Allene
Chemistry, Wiley-VCH, Weinheim, 2004; For selected papers
on the synthesis of allenes, see: (g) Q. Liu, T. Cao, Y. Han,
X. Jiang, Y. Tang, Y. Zhai and S. Ma, Copper(I) Iodide-
Catalyzed Asymmetric Synthesis of Optically Active Tertiary
α-Allenols, Synlett, 2019, 477–482; (h) J. Ye, S. Li, B. Chen,
W. Fan, J. Kuang, J. Liu, Y. Liu, B. Miao, B. Wan, Y. Wang,
X. Xie, Q. Yu, W. Yuan and S. Ma, Catalytic Asymmetric
Synthesis of Optically Active Allenes from Terminal
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Click Reaction: Self-Assembly of Triazole Fused
Organic & Biomolecular Chemistry
[1,2,3]Triazolo[1,5-a]quinoline. Synthesis of 8-Haloquinolin-
2-carboxaldehydes, Tetrahedron, 2009, 65, 4410–4417;
(b) A. Joshi, R. Semwal, E. Suresh and S. Adimurthy, Pd-
Catalyzed Regioselective Synthesis of 2,6-Disubstituted
Pyridines through Denitrogenation of Pyridotriazoles and
Isoindolines, Chem. Commun., 2016, 52, 13163–13166.
12 For azide–allene [3 + 2]cycloaddition, see: (a) T. G. Back,
K. N. Clary and D. Gao, Cycloadditions and Cyclizations of
Acetylenic, Allenic, and Conjugated Dienyl Sulfones, Chem.
Rev., 2020, 110, 4498–4553; (b) S. Børresen and J. K. Crandall,
Reaction of Picryl Azide with Aryloxyallenes, J. Org. Chem.,
1976, 41, 678–681; (c) D. K. Wedegaertner, R. K. Kattak,
I. Harrison and S. K. Cristie, Aryl Azide-Allene Cycloaddition.
The Contrasting Behavior of Two Simple Allenes, 1,2-
Cyclononadiene and 1,2-Propadiene, J. Org. Chem., 1991, 56,
4463–4467; (d) C. Mukai, M. Kobayashi, S. Kubota,
Y. Takahashi and S. Kitagaki, Construction of Azacycles
Based on Endo-Mode Cyclization of Allenes, J. Org. Chem.,
2004, 69, 2128–2136; (e) F. Sebest, L. Casarrubios, H. S. Rzepa
and A. J. P. White, Diez-González, S. Thermal Azide–alkene
Cycloaddition Reactions: Straightforward Multi-Gram Access
to Δ2-1,2,3-Triazolines in Deep Eutectic Solvents, Green
Chem., 2018, 20, 4023–4035; (f) X. Duan, X. Huang, C. Fu
and S. Ma, Palladium–Catalyzed Selective Three–Component
Tandem Reaction to Bicyclic 1,2,3−Triazole Derivatives, Adv.
Synth. Catal., 2019, 362, 627–647.
3,8-Diarylation
of
Imidazo[1,2-a]pyridines,
Chem.
Commun., 2019, 55, 10888–10891; (c) D. Lamaa, H.-P. Lin,
T. Bzeih, P. Retailleau, M. Alami and A. Hamze,
TBAB-Catalyzed Csp3−N Bond Formation by Coupling
Pyridotriazoles with Anilines: A New Route to (2-Pyridyl)
alkylamines, Eur. J. Org. Chem., 2019, 2602–2611;
(d) J. Panteleev, R. Y. Huang and M. Lautens, Addition of
Arylboronic Acids to Arypropargyl Alcohols en Route to
Indenes and Quinolines, Org. Lett., 2011, 13, 5314–5317;
(e) B. Lü, C. Fu and S. Ma, Application of a Readily
Available and Air Stable Monophosphine HBF4 Salt for the
Suzuki Coupling Reaction of Aryl or 1-Alkenyl Chlorides,
Tetrahedron Lett., 2010, 51, 1284–1286; (f) B. Lü, C. Fu and
S. Ma, Application of Dicyclohexyl-(S)-trimethoxyphenyl
Phosphine HBF4 Salt for the Highly Selective Suzuki
Coupling of the C−Cl Bond in β-Chlorobutenolides Over
the More Reactive Allylic C−O bond, Chem. – Eur. J., 2010,
16, 6434–6437; (g) R. Zeng, S. Wu, C. Fu and S. Ma, Room-
temperature Synthesis of Trisubstituted Allenylsilanes via
Regioselective C−H Functionalization, J. Am. Chem. Soc.,
2013, 135, 18284–18287.
13 CCDC 2078447† contains the supplementary crystallo-
graphic data for the structure.
14 (a) R. Ballesteros-Garrido, F. R. Leroux, R. Ballesteros,
B. Abarca and F. Colobert, The Deprotonative Metalation of
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