Copper-Catalyzed Selective N-Arylation of Oxadiazolones by Diaryliodonium Salts

Article abstract of DOI:10.1002/adsc.202100426

Here, we report the method for copper-catalyzed N-arylation of diverse oxadiazolones by diaryliodonium salts under mild conditions in high yields (up to 92%) using available CuI as a catalyst. The developed method allows utilizing both symmetric and unsymmetric diaryliodonium salts bearing auxiliary groups such as 2,4,6-trimethoxyphenyl (TMP). We found that the steric effects in aryl moieties determined the chemoselectivity of N- and O-arylation of the 1,2,4-oxadiazol-5(4H)-ones. Mesityl-substituted diaryliodonium salts demonstrated the high potential as a selective arylation reagent. The structural study suggests that steric accessibility of N-atom in 1,2,4-oxadiazol-5(4H)-ones impact to arylation with sterically hindered diaryliodonium salts. The synthetic application of proposed method was also demonstrated on selective arylation of 1,3,4-oxadiazol-2(3H)-ones and 1,2,4-oxadiazole-5-thiol. (Figure presented.).

Full text of DOI:10.1002/adsc.202100426

RESEARCH ARTICLE
DOI: 10.1002/adsc.202100426
Copper-Catalyzed Selective N-Arylation of Oxadiazolones by
Diaryliodonium Salts
Natalia S. Soldatova,a, b,* Artem V. Semenov,c, d Kirill K. Geyl,a
Sergey V. Baykov,a,* Anton A. Shetnev,e Anna S. Konstantinova,f
Mikhail M. Korsakov,f Mekhman S. Yusubov,b and Pavel S. Postnikovb, g,*
a
Institute of Chemistry, Saint Petersburg State University,
Saint Petersburg 199034, Russian Federation
E-mail: n.soldatova@spbu.ru; s.baykov@spbu.ru
Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University,
b
Tomsk 634034, Russian Federation
E-mail: postnikov@tpu.ru
M.V. Lomonosov Institute of Fine Chemical Technologies,
c
MIREA – Russian Technological University,
86 Vernadskogo Pr, Moscow 119571, Russian Federation
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry,
d
16/10 Miklukho-Maklaya St., Moscow 117997, Russian Federation
Pharmaceutical Technology Transfer Centre,
e
Yaroslavl State Pedagogical University named after K.D. Ushinsky,
108 Respublikanskaya St., Yaroslavl 150000, Russian Federation
Russian State University named after A.N. Kosygin (Technology. Design. Art),
f
33 Sadovnicheskaya St., Moscow 117997, Russian Federation
Department of Solid State Engineering, Institute of Chemical Technology,
g
Prague 16628, Czech Republic
Manuscript received: April 5, 2021; Revised manuscript received: May 23, 2021;
Version of record online: ■■■, ■■■■
Supporting information for this article is available on the WWW under https://doi.org/10.1002/adsc.202100426
Abstract: Here, we report the method for copper-catalyzed N-arylation of diverse oxadiazolones by
diaryliodonium salts under mild conditions in high yields (up to 92%) using available CuI as a catalyst. The
developed method allows utilizing both symmetric and unsymmetric diaryliodonium salts bearing auxiliary
groups such as 2,4,6-trimethoxyphenyl (TMP). We found that the steric effects in aryl moieties determined the
chemoselectivity of N- and O-arylation of the 1,2,4-oxadiazol-5(4H)-ones. Mesityl-substituted diaryliodonium
salts demonstrated the high potential as a selective arylation reagent. The structural study suggests that steric
accessibility of N-atom in 1,2,4-oxadiazol-5(4H)-ones impact to arylation with sterically hindered diary-
liodonium salts. The synthetic application of proposed method was also demonstrated on selective arylation of
1,3,4-oxadiazol-2(3H)-ones and 1,2,4-oxadiazole-5-thiol.
Keywords: Iodonium salts; Arylation; Amides; Heterocycles; Chemoselectivity
Introduction
and medicinal chemistry.[1–4] Due to this reason, the
development of new approaches and methods to the
Heterocyclic compounds are a pivotal class of organic synthesis of heterocyclic core and its modification can
substances, which widely spread among natural and be considered as an essential task for organic
artificial products. Nitrogen-containing heterocyclic chemistry.[5]
compounds are found in such substances as α-amino
One of the promising classes of heterocyclic
acids and peptides, DNA, RNA, while the high affinity organic compounds is oxadiazolones, revealing versa-
of N-heterocyclic compounds to biological molecules tile biological activity (Figure 1). For instance, 1,3,4-
allows implementing it in drug design, pharmacology, oxadiazol-2(3H)-one based compounds have been
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Figure 1. Examples of biologically active oxadiazolones.
applied for the treatment of type 2 diabetes and
dementia (Capeserod).[6,7] The derivative of 1,2,4-
oxadiazol-4(5H)-ones, Azilsartan medoxomil, is regis-
tered as a drug for the therapy of hypertonia.[8] Another
example of perspective targets is 3-(2-meth-
oxyphenyl)-4-(3-(trifluoromethyl)phenyl)-1,2,4-oxa-
diazol-5(4H)-one demonstrating HIV inhibition
activity.[9] Despite the broad applicability of oxadiazo-
lones, the further evaluation of the biological activity
of these compounds can be hampered due to limited
numbers of synthetic approaches and methods of late-
Scheme 1. Synthetic pathways to N-arylated 1,2,4-oxadiazol-
5(4H)-ones.
stage modification, including N-arylation of 1,2,4- between aryne precursor and 1,2,4-oxadiazol-5(4H)-
oxadiazol-4(5H)-ones. ones. This approach has notably high chemoselectivity
The reported synthesis of N-arylated 1,2,4-oxadia- of N/O-arylation in dependence on the presence of Ag-
zol-5(4H)-one can be separated into two main ap- catalyst. Despite this, the main drawbacks of this
proaches: a) condensation of N-hydroximoyl chlorides; method are the low regioselectivity of arylation by
and b) direct arylation of 1,2,4-oxadiazol-5(4H)-one substituted aryne precursors, low synthetic availability
core (Scheme 1). The first approach was reported in and relatively high cost of ortho-(trimethylsilyl)phenyl
the XIX century and consumed condensation of N- triflates.
hydroximoyl chlorides and anilines with the formation
We proposed that diaryliodonium salts are able to
of N’-hydroxy-N-arylbenzimidamide following carbox- be a source of electrophilic aryl intermediates in the
ylation with phosgene, ethyl chloroformate, or 1,1’- reaction with 1,2,4-oxadiazol-5(4H)-ones similarly to
carbonyldiimidazole.[10–12] Recently, Sharma et al. re- arylation of various nucleophiles demonstrated
ported a convenient way for the construction of 1,2,4- previously.[15–17] The hypervalent iodine reagents are
oxadiazol-5(4H)-one core via interaction of cyana- widely used for the transfer of alkynyl-,[16,18–20] alkenyl-
mides and N-hydroximoyl chlorides with the formation
,
[16,21,22] aryl groups,[16,23–26] etc.[27] Particularly important
of 1,2,4-oxadiazol-5(4H)-imine, which was readily the direct arylation of various nucleophiles by diary-
converted to 1,2,4-oxadiazol-5(4H)-one by simple liodonium salts. Thus, the strong nucleophiles are able
hydrolysis.[13]
to react with electron-poor aryl electrophile without
To the best of our knowledge, the direct arylation the addition of transition metals (for instance,
of 1,2,4-oxadiazol-5(4H)-ones is investigated poorly. amines,[28–31] alkoxides,[32–34] S-nucleophiles,[35,36] etc.).
The formation of arylated derivatives was demon- The weaker nucleophiles require higher temperatures
strated by Wang et al. in 2018[14] in the reaction or the addition of transition metals, especially
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copper.[24] The particular interest has been appealed by The developed approach displays the high applicability
the N-arylation of heterocycles. The electron-rich for the functionalization of both 1,2,4-oxadiazol-
heterocycles can be arylated by iodonium salts in 5(4H)-ones and 1,3,4-oxadiazol-2(3H)-ones bearing
relatively mild conditions,[37–40] while electron-poor various substituents. Moreover, the evaluation of
(especially cyclic amides and related compounds) auxiliary group effects in unsymmetrical iodoniums
require the addition of catalyst.[41–46] Also, the synthetic salts demonstrated the high regioselectivity of inter-
procedures for preparing diaryliodonium salts make action with readily available aryl(mesityl)iodonium
available the versatile scope of these compounds with salts.
high yields from common laboratory reagents.[47–54]
Nevertheless, the chemoselectivity of arylation of
N,O-containing heterocycles presents a challenging
Results and Discussion
task in hypervalent iodine chemistry. For instance, We initially evaluated prospects of the arylation of 1a
selective N- and O-arylation of pyridine-2-ones was employing diphenyliodonium triflate 2a. Indeed, the
problematic[58,59] until a recent report, where base-tuned current trends in the arylation of N-centered nucleo-
chemoselectivity has been applied.[60] It should also be philes consume metal-free conditions, but the low
noted that the arylation of weak nucleophiles by nucleophilicity of 1a did not favor the direct arylation
iodonium salts represents a complex task, which (Table 1, Entries 1–4). In order to find suitable con-
affects the synthetic applicability of hypervalent iodine ditions, we added CuI as a cheap and available
reagents.
catalyst, which has been already applied for the
In the proposed contribution, we report a mild and arylation of hydantoins,[42] 2,7-naphthyridin-1(2H)-
effective arylation procedure of oxadiazolones by one,[43] and other weak N-centered nucleophiles.[15,61]
symmetrical and unsymmetrical diaryliodonium salts. The addition of 10 mol% CuI in the presence of
Table 1. Optimization of the arylation of 3-(p-tolyl)-1,2,4-oxadiazol-5-one with diphenyliodonium salts.[a]
°
Entry
XÀ
Base, (1.5 equiv.)
Solvent
T, C
Cat., (mol%)
Yield,[b]
%
1
2
3
4
5
6
7
8
TfOÀ
TfOÀ
TfOÀ
TfOÀ
TfOÀ
TfOÀ
TfOÀ
TfOÀ
TfOÀ
TfOÀ
TfOÀ
TfOÀ
TfOÀ
TfOÀ
TfOÀ
CF3COOÀ
tBuONa
aq. NH3
Cs2CO3
NaOH
tBuONa
aq. NH3
Cs2CO3
NaOH
NaOH
NaOH
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
MeCN
rt.
rt
rt
rt
rt
rt
rt
rt
60
80
60
60
60
60
60
60
60
60
60
60
None
None
None
None
NR[c]
NR[c]
NR[c]
NR[c]
NR[c]
NR[c]
2
CuI, (10)
CuI, (10)
CuI, (10)
CuI, (10)
CuI, (10)
CuI, (10)
CuI, (10)
CuBr, (10)
CuBF4 (MeCN)4
Cu(OTf)2
CuI, (10)
CuI, (10)
CuI, (10)
CuI, (10)
CuI, (10)
CuI, (5)
6
9
77(59)[d]
44
10
11
12
13
14
15
16
17
18
19
20
83
76
82
65
80
77
83
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
À
BF4
BrÀ
19
TfOÀ
TfOÀ
58[e]
52
Et3N
[a] Reaction conditions: 1a (0.5 mmol), 2a (0.75 mmol), of 2a, base (0.75 mmol) in 5 mL of solvent for 24 h in Ar.
[b] Isolated yield.
[c] According to TLC.
[d] Reaction performed in air.
[e] 0.625 mmol of 2a was used.
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Cs2CO3 or NaOH furnished 3 in low yields (Table 1,
The reaction proceeded smoothly with oxadiazo-
Entries 5–8). The increase of reaction temperature up lone 1j bearing competitive nucleophilic center as the
°
to 60 C allowed the isolation of 3 in a better yield AcNH-group. We did not observe the arylation of
(77%, Table 1, Entry 9), but a further increase of acetamido group, which evidenced high chemoselec-
°
temperature (up to 80 C) led to the decrease the yield tivity of reaction. Nevertheless, the yield of target 3ja
(44%; Table 1, Entry 10). In view of that, the heating was slightly lower (61%). The suggested approach was
of the reaction mixture up to 60 C was considered as also applicable for the functionalization of oxadiazo-
an optimal. Under such conditions, we attempted to lones containing heterocyclic (1m) and alkyl moieties
avoid the use of argon, but the reaction conducted in (1n–o). In both cases, the desired products were
air resulted in a significant yield drop (59%; Table 1, isolated in good yields (3ma 77%, 3na 85%, and 3oa
Entry 9). In the next stage, we changed the NaOH to 82%).
°
the triethylamine, which allowed the isolation of target
The evaluation of scope using symmetrical iodo-
3 in 83% yield (Table 1, Entry 11). The reaction was nium salts displays high acceptability toward halo-
not sensitive to solvent and the anion in the catalyst substituted diaryliodonium salts 2b–c provided 3 in
(Table 1, Entries 12–13, 15). An only slight decrease higher yield for most substrates compared with 2a (the
of the yield (approximately 5%) was observed in the only exception 3gc). In contrast, reaction with diary-
case of CuBr (Table 1, Entry 12). However, utilization liodonium salt 2d bearing electron-withdrawing
of Cu(II)-catalyst decrease the yield down to 65% groups (CF3) proceeded with lowered yield (3dd,
(Table 1, Entry 14). The reaction was tolerant of the 67%; 3ld, 30%). Unsuccessful arylation was observed
non-coordinating anions in diaryliodonium salt (Ta- for dibenziodolium triflate that resulted in the decom-
ble 1, Entries 16–17). However, in the case of position of iodonium salt with the formation of 2-
diphenyliodonium bromide, the yield dramatically iodobiphenyl. Besides the electronic effect in diary-
drops to 19% due to competitive arylation of bromide- liodonium salts 2, the steric accessibility affects both
anion (Table 1, Entry 18). The proposed method was reaction pathways and product yields. In the case of
sensitive to the amounts of reacting compounds. Thus, sterically hindered 2e having 2,5-xylyl-group, yields
the addition of 5 mol% of the catalyst (Table 1, of 3 decreased by approximately 10–20%. The bulkier
Entry 20) or decreased amount of 2a (Table 1, mesityl-derived iodonium salts 2f reacted differently
Entry 19) led to a sufficient decrease the yield of 3.
depend on steric effects in 1. Notable that for ortho-
The best result was achieved (Table 1, Entries 11 substituted 1c,f,l the corresponding product was
and 17) when 2a or 2aBF4 were used as the aryl- prepared selectively in high yield for 3cf (82%) and
source. In a further study, we used diaryliodonium moderate yield for 3ff and 3lf (62% and 43%
triflates due to the convenience of its preparation using correspondingly). In contrast, the interaction of less
Oxone[53,54] or mCPBA[62,63] as oxidants.
sterically hindered 1 with 2f, afforded both N-arylated
With optimized conditions in hands, we evaluated and O-arylated products with low yields (<27%)
the scope and limitations of the proposed method using (Scheme 3). Evaluation of results does not reveal any
1,2,4-oxadiazol-5(4H)-ones 1a–o and symmetric dia- dependence of yield and products ratio on electron
ryliodonium salts 2a–f (Scheme 2). The arylation of effects of substituents in 1.
1a–o by 2a demonstrated the good tolerance to
Notably, the molecular structure of seven com-
electronic and steric effect of substituents in 1,2,4- pounds 3 was confidently confirmed by single-crystal
oxadiazol-5(4H)-one. 3-Aryl-1,2,4-oxadiazol-5(4H)- XRD analysis. The obtained crystal structure of 3 can
ones 1a–g,i,k bearing moderate electron-withdrawing indirectly explain observed selectivity for ortho-sub-
and electron-donating substituents reacted with 2a to stituted 1c,f,l that exhibited larger angle between plane
give high yields of arylation products 3aa–ga,ia,ka normals (ffα) of aryl ring (belong to 1), and 1,2,4-
(>82%). Only for the NO2-substituent we observed a oxadiazol-5-one rings in 3. For instance, in ortho-
°
slight decrease of product yield (70%), probably, due substituted 3fa,ff,lb it is more than 55 , while in para-
to the limited solubility of 1h. Particularly important, substituted 3ea and 3ka, and in reported structure 3ba
the reaction involving sterically-hindered ortho-substi- (CDS code: FOVVUH01)[13] the ffα less 36 . The plane
°
tuted oxadiazolones 1c,f as reactants proceeded angles in the product can explain the steric hindrance
smoothly to provide 3ca and 3fa in high to excellent for bulky mesityl species (Figure 2, a–b). Notably, that
yields (86% and 92% correspondingly). The sufficient in cases when the phenyl ring rotated oppositely, the
°
decrease of yield was observed only for ortho-OMe determined ffα is more than 90 we used for compar-
°
substituted 1l, and product 3la was isolated in 63% ison calculated adjacent angle (180 –ffα) (Figure 2, c–
yield. Looking ahead, we consider that ortho-OMe d). Moreover, observed selectivity N,O-arylation of
substituted oxadiazolone 1l demonstrated lower reac- para-substituted with 2f can be explained by lower
tivity in the reaction with other iodonium salts steric hindrance of O-atom compared to N-atom in
(3lb,ld,lf).
combination with kinetic features of reaction to lower
nucleophilicity of oxygen than nitrogen.
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Scheme 2. Scope of arylation of 1,2,4-oxadiazol-5(4H)-ones 1a–o by symmetric diaryliodonium salts 2a–f (Top panel); single
crystal XRD structures of products 3 (Bottom panel, the detailed description is provided in SI).[a,b]
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Scheme 3. Arylation of 1,2,4-oxadiazol-5(4H)-one 1 with 2f.[a,b]
steric or electronic effects in iodonium salts[64] or
external physical triggers such as plasmon
resonance.[65] However, the application of unsymmet-
rical iodonium salts can access arylation products,
which are difficult to prepare using symmetrical
iodonium salts due to synthetic limitations. For
instance, preparation of symmetrical iodonium salts
bearing electron-withdrawing groups proceed in low
yields and often required expensive reagents as
corresponding boronic acid.[66,67] Similar issues are
revealed in the case of challenging regiospecific syn-
thesis of symmetrical iodonium salts.
Previously, Stuart et al. reported the preparation and
synthetic applicability of aryl(2,4,6-trimethoxyphenyl)
iodonium salts as selective arylation agents for various
nucleophiles (C, N, O, and S).[50,51,68] We tested readily
accessed phenyl(2,4,6-trimethoxyphenyl)iodonium to-
sylates and trifluoroacetates for arylation of 1a. In
both cases, we succeeded in isolation of desired
products with a slightly higher yield of 3aa (85%)
(Table 2, Entries 1–3). Our previous results in arylation
by bis(mesityl)iodonium salt 2f were promising for
aryl(mesityl)iodonium salts as a selective reagent for
Figure 2. Steric accessibility of N-atom in dependence on
angles between plane normals.
Based on experimental results and previous arylation of 1. Indeed, utilization of 2i leads to
reports[24,42,46] we proposed the mechanism of the N- selective formation of 3aa in the highest yields (87%).
and N/O-arylation of 1,2,4-oxadiazol-5-ones (Sche-
Further comparison of iodonium salts reactivity
me 4,a). Plausible mechanism includes the oxidative demonstrated that utilization of unsymmetrical iodo-
addition of CuI complex with Et3N to diaryliodonium nium salts bearing electron-withdrawing substituent as
salt following ligand exchange with deprotonated CF3-group was more efficient and led to the sufficient
oxadiazolone and reductive elimination (Scheme 4,a). increase of yields up to 86% (reaction of 2d gave 3dd
In the case of N/O-arylation of 1, we suppose that the only in 67% yield – (Scheme 2)). Nevertheless, the
attack of product of oxidative addition is hampered for application of mesityl-substituted iodonium salts (such
N-nucleophilic site due to steric hindrance. Thus, the as 2k) led to the formation of O-arylated product in
kinetically controlled product of O-arylation has been low yield (compound B, Table 2), hampering the
formed in the more considerable amount (Scheme 4,b) isolation of A.
In the next step, we tested the applicability of the
unsymmetrical iodonium salts in the arylation of 1a utilization
We found a few more reasons for the preferable
of 2,4,6-trimethoxyphenyl-substituted
under optimized conditions (Table 2, Entries 1–4). The (TMP-substituted) iodonium salts instead of mesityl
main drawback of unsymmetrical iodonium salts is ones. First of all, TMP-substituted iodonium salt
connected with regioselectivity issues controlled by bearing NO2-group 2l was more reactive over mesityl-
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Scheme 4. Plausible mechanism of arylation of 1,2,4-oxadiazol-5-ones with diaryliodonium salts.
analog 2m (80% vs. 53% yield of 3al). Similar 3ld product. 3-(2-Methoxyphenyl)-4-(3-(trifluorometh-
behavior has been demonstrated in the arylation of yl)phenyl)-1,2,4-oxadiazol-5(4H)-one 3ld has been
oxadiazolone 1l by 2j and 2k with the formation of proved as a potent anti-human immunodeficiency virus
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Table 2. Optimization and initial evaluation of arylation of 1,2,4-oxadiazol-5(4H)-one 1 by unsymmetrical iodonium salts.[a]
Entry Substrates
1, R1
Time, h Yield of A,[b]
%
Yield of B, % Yield of C, %
2, R2
Aux
X–
1
2
3
4
5
6
7
8
9
10
1a, 4-Me
2g, H
2h, H
2h, H
TMP
TMP
TMP
TsOÀ
5
5
3aa, 74
3aa, 78
3aa, 85
3aa, 87
3dd, 82
3dd, 86c)
3ld, 75
3ld, 43c)
3al, 80
–
–
–
–
-
–
–
–
–
–
–
–
CF3COOÀ
CF3COOÀ 24
2i, H
2,4,6-(Me)3C6H2 TfOÀ
24
CF3COOÀ 24
2,4,6-(Me)3C6H2 TfOÀ
24
TMP
CF3COOÀ 24
2,4,6-(Me)3C6H2 TfOÀ
24
TMP
CF3COOÀ 24
2m, 4-NO2 2,4,6-(Me)3C6H2 TfOÀ
24
1d, 3-Me
2j, 3-CF3
2k, 3-CF3
TMP
–
9[c]
–
1l, 2-OMe 2j, 3-CF3
2k, 3-CF3
1a, 4-Me
7[c]
–
2l, 4-NO2
–
3al, 53c)
6[c]
4[b]
[a] Conditions: 0.5 mmol of 1, 0.75 mmol of 2, 0.75 mmol of Et3N, 10 mol% CuI in 5 mL of 1,2-DCE in Ar atmosphere.
[b] Isolated yield.
[c] According to the NMR experiments.
(HIV) molecule.[9] Our initial experiments with sym-
metric iodonium salts allowed to isolate 3ld in 30%
yields (Scheme 2). Implementation of TMP-substituted
iodonium salt 2j resulted only in 43% (Table 2,
Entries 7 and 8). Overall, albeit mesityl-substituted
iodonium salt in some cases demonstrated better yield
than TMP-substituted iodonium salt, the utilization of
the last ones sufficiently increased the yield of 3ld up
to 75%, while the use of mesityl-substituted iodonium
salt 2k ones led to more sustainable results in both
selectivity and yield of arylation.
The evaluation of iodonium salts reactivity allowed
us to sufficiently improve the yields of products 3
compared to symmetrical iodonium salts. Thus, we
successfully prepared the arylated oxadiazolones 3al–
ks using unsymmetrical 2l,n–s with better yields (68–
88%) (Scheme 5). The yield of product does not
depend on the electronic effects of substituents in the
para-position of diaryliodonium salts The reaction
proceeded smoothly with electron-withdrawing (3al,
80%; 3kq, 70%) and electron-donating groups (3cn,
68%; 3gp 77%). The reaction with meta-substituted
iodonium salts 2j,o,r give good yields (3fo, 72%; 3ar
81%). However, in the case of sterically hindered
ortho-chlorophenyl-substituted iodonium salt 2s, the
desired product 3cs was isolated in lower yield 19%
for ortho-substituted oxadiazolone 1c and in trace
amount for 1b. The decrease of yield is in agreement
Scheme 5. Arylation of 1,2,4-oxadiazol-5(4H)-one 1 by unsym-
metrical diaryliodonium salts 2.[a,b]
To our delight, the reaction‘s scope could be
with the behavior of sterically hindered diaryliodonium extended to 1,3,4-oxadiazol-2(3H)-ones 5 (Scheme 6,
salt 2f and reported data about arylation of N- a). The published approaches to arylation of 1,3,4-
nucleophiles
with
TMP-substituted
iodonium oxadiazol-2(3H)-ones limited only to corresponding 5-
salts.[37,39,42]
alkyl-derivatives prepared by interaction with haloar-
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Scheme 6. Arylation of 1,3,4-oxadiazol-2(3H)-ones 5 and 3-(p-tolyl)-1,2,4-oxadiazole-5-thiol 7 by symmetric diaryliodonium
salts.[a,b]
enes under harsh conditions.[69,70] The application of smoothly, and product 8 was formed after 1 h of
the developed procedure allowed to isolate the appro- stirring. Notable, that arylation of 3-(aryl)-1,2,4-
priate derivatives 6 in good yields (>65%) independ- oxadiazole-5-thiol is unknown and proposed procedure
ently from the electronic and steric effect of substitu- can be effective tool for synthesis of 5-(arylthio)-3-
ents in 5 The products 6b and 6f was obtained (aryl)-1,2,4-oxadiazoles.
selectively in high yield (86 and 84% correspondingly)
albeit the use of sterically hindered iodonium salts 2e
and 2f. Obviously, the efficiency of reaction with 5
Conclusion
revealed a similar to 1 pattern and proceeded smoothly In conclusion, we have developed the method for the
for most substrates. In further experiments, we exam- N-arylation of oxadiazolones derivatives with symmet-
ined the synthetic applicability of the method for ric and unsymmetric diaryliodonium salts under mild
arylation of 3-(p-tolyl)-1,2,4-oxadiazole-5-thiol
7
conditions using inexpensive CuI as a catalyst. The
(Scheme 6, b). The soft nucleophilic nature of S-center utilization of symmetric and unsymmetric diaryliodo-
in 7 sufficiently changed the reaction selectivity nium salts sufficiently facilitates access to valuable
towards S-arylation.[35] The reaction proceeded arylated cyclic amides. Impact of steric effects in
Adv. Synth. Catal. 2021, 363, 1–12
9
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RESEARCH ARTICLE
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iodonium salts as an alternative to highly selective aryl
(TMP)iodonium salts. The proposed method facilitates
access to novel derivatives of oxadiazolones, including
N-arylated 1,2,4-oxadiazol-5(4H)-ones and 1,3,4-oxa-
diazol-2(3H)-ones, and S-arylated 1,2,4-oxadiazole-5-
thiols. We believe that the proposed approach is able to
increase the synthetic applicability of iodonium salts
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Experimental Section
General procedure for the preparation of 3, 4, 6. The solution of
triethylamine (0.75 mmol, 104 μL) in 1,2-DCE (5 mL) was
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Acknowledgements
This work was funded by the Russian Science Foundation, grant
number 19-73-00007 (the development of method and reactivity
study), and by the Ministry of Science and Higher Education of
Russian Federation in frame of the “Mega-grant” project,
application number 2020-220-08-8827 (preparation of iodo-
nium salts and XRay study). The authors are grateful to the
Center for X-ray Diffraction Studies, Magnetic Resonance
Research Center, and Center for Chemical Analysis and
Materials Research (all belonging to Saint Petersburg State
University) for the physicochemical studies.
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RESEARCH ARTICLE
Copper-Catalyzed Selective N-Arylation of Oxadiazolones by
Diaryliodonium Salts
Adv. Synth. Catal. 2021, 363, 1–12
N. S. Soldatova*, A. V. Semenov, K. K. Geyl, S. V. Baykov*,
A. A. Shetnev, A. S. Konstantinova, M. M. Korsakov, M. S.
Yusubov, P. S. Postnikov*