N1- and N3-Arylations of Hydantoins Employing Diaryliodonium Salts via Copper(I) Catalysis at Room Temperature

Article abstract of DOI:10.1002/ejoc.202001353

Copper(I)-catalyzed N-arylation (both N¹- and N³-) of hydantoins with diaryliodonium salts as aryl partners at room temperature is reported. The transformation allows diverse scopes on both hydantoins and diaryliodonium salts deliver

Full text of DOI:10.1002/ejoc.202001353

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N1- and N3-Arylations of Hydantoins Employing
Diaryliodonium Salts via Copper(I) Catalysis at Room
Temperature
Raktim Abha Saikia,[a] Dhiraj Barman,[a, b] Anurag Dutta,[a] and Ashim Jyoti Thakur*[a]
Dedicated to Prof. Viktor V. Zhdankin for his outstanding contribution to Hypervalent Iodine Chemistry.
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Copper(I)-catalyzed N-arylation (both N1- and N3-) of hydantoins
with diaryliodonium salts as aryl partners at room temperature
is reported. The transformation allows diverse scopes on both
hydantoins and diaryliodonium salts delivering functionalized
N3-arylated products under mild reaction conditions. The
presence of hydrogens at C5- and N1- position of the hydantoin
does not lead to other side products. Chiral hydantoins can also
be synthesized via this methodology. Sterically complicated
ortho-substituted diaryliodonium salts are tolerated and deliv-
ered challenging ortho-arylated products. In addition, this
strategy can also be effectively extended to N1-arylation of
hydantoins.
Introduction
Biologically active arylated hydantoin (imidazolidine-2,4-dione)
derivatives[1] have marked skeletal appearances in a wide array
of natural products[2] and synthetic products.[3] This motif is
purposely and effectively used in medicinal chemistry,[4] coordi-
nation chemistry,[5] agrochemistry,[6] and polymer sciences.[7]
Though, structurally simple and first synthesized[8] in 1861,
intense research efforts have been devoted to synthetic
developments and studies of this class of five-membered
compound.[1a] Hydantoin based drugs such as Nilutamide (1)
and Enzalutamide (3) (Figure 1) have been used as anti-
androgen and anti-prostate cancer agents respectively. GLGP-
0492 (2), BMS-587101 (4), and BMS-564929 (5) are candidates
under clinical development (Figure 1).
Figure 1. Important hydantoin based drugs.
In the traditional approach, condensation of aryl isocyanates
with amino acid derivatives afforded N3-arylated hydantoins
(Scheme 1a).[9] This strategy required strong acidic or basic
conditions during the cyclization of ureido derivatives. More-
over, substituted aryl isocyanates needed extra steps for their
syntheses. Moreover, isocyanates are often toxic and unstable
under ambient conditions.[10]
partners in Cu-mediated protocols (Scheme 1b). Recently, Petit’s
group re-established the Cu-mediated N3-arylation and subse-
quently Cu-catalysed N1-arylation of N3-aryl hydantoins using
aryl halides (Scheme 1c).[14] Although the method highlighted
broad substrate scopes, ortho-substituted aryl groups failed to
tolerate the reaction condition. Also, N3-arylation of hydantoins
containing both acidic C5À H and N1À H exhibited poor selectivity
and hence limited hydantoins were studied.
Diaryliodonium salts have emerged as a versatile arylating
partner over the past decades because of their ease of
synthesis, less environmental impact, affordability, and reactiv-
ity within a wide range of nucleophiles.[15] Owing to the
presence of an excellent leaving group (aryl iodide), diary-
liodonium salts have encompassed their importance in metal-
free and transition-metal catalyzed arylation chemistry.[16]
Arylation of lactams and primary amides with diaryliodonium
salts with the aid of Cu-catalysis has been achieved.[17] Pioneer-
ing works on metal-free arylation of a wide range of secondary
amides have been reported by Olofsson’s group.[18] But,
hydantoins (containing imide and amide functional groups)
Menendez et al. pioneered Cu-mediated N3-arylation of
hydantoins (only one example) with p-tolyllead triacetate[11] as
an arylating source. Thereafter, triarylbismuthane,[12] aryl bor-
onic acid,[12] and aryl iodide[13] were also employed as aryl
[a] R. Abha Saikia, D. Barman, A. Dutta, Prof. A. Jyoti Thakur
Department of Chemical Sciences
Tezpur University
Napaam-784028, Assam, India
E-mail: ashim@tezu.ernet.in
http://www.tezu.ernet.in/dcs/personal_profile_ajt.html
[b] D. Barman
Department of Chemistry
Shiv Nadar University
Greater Noida-201314, Uttar Pradesh, India
Supporting information for this article is available on the WWW under
https://doi.org/10.1002/ejoc.202001353
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Scheme 1. Strategies for N3-arylation of hydantoins.
have not been extensively discussed in the report.[19] Recently,
Cu-catalysed N3-arylation has been reported utilizing aryl(TMP)
OTs, as the aryl source with a broad substrate scope in the aryl
part (Scheme 1d).[20] In this first Cu-catalysed protocol, they
metrical salts) and 4) non-interfering iodonium salts (triflate &
tertrafluoroborate) (Scheme 1e).
highlighted the efficiency of regioselective arylation without Results and Discussion
epimerization at C5- and N1- position of hydantoins, even
though an excess amount of iodonium salts were utilized and
trace amounts of both N1-regiomer and N1,N3-biarylated side
products were observed. However, highly congested ortho-
substituents were also not tolerated under this protocol.
Considering the limitations of existing methodologies for
the arylation of hydantoins, we have come up with a mild
protocol for N-arylation (both N1- and N3-) of hydantoins with
diaryliodonium salts as the arylating partner. Our protocol
compatibility of congested ortho-substituted substrates exhibits
the advantages of 1) room temperature reaction, 2)compatibil-
ity of congested ortho-substituted substrates (Sandtorv’s ob-
served only one example with less yield), 3) lower stoichiometry
(~1 equiv.) of iodonium salt (both in symmetrical and unsym-
N3-Arylation of hydantoins with diaryliodonium salts:
We embarked on our initial optimization of the reaction
conditions using diphenyliodonium triflate (2a) as the aryl
source and 5,5-dimethylhydantoin (1a) as the model substrates
(Table 1). No arylation was observed under base-mediated
conditions and in the absence of Cu catalyst (see ESI, Table S3).
Initially, arylation at N3-position was obtained when the reaction
was conducted utilizing a stoichiometric amount of copper(I)
°
iodide and Na2CO3 at room temperature (30 C) affording the
desired product (3a) in 74% yield (entry 1). Reducing the
amount of copper to a catalytic scale (entry 2) took a longer
time for completion along with decomposition of the iodonium
salt and the yield came down to 45%. Different solvents and
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Table 1. Optimization with diphenyliodonium salts.[a]
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°
Entry
Solvent
Base (equiv.)
Cu [xmol%]
T [ C]
Time [h]
Yield [%][b]
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2
3
4
5
6
7
8
DCE
DCE
DCE
DCE
DCE
DCE
Toluene
DMF
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
Na2CO3 (1.0)
Na2CO3 (1.0)
Na2CO3 (2.0)
Et3N (1.0)
K3PO4 (1)
K3PO4 (2)
K3PO4 (1)
K3PO4 (1)
Cs2CO3 (1)
tBuOK
K3PO4 (1)
K3PO4 (1)
K3PO4 (1)
K3PO4 (1)
K3PO4 (1)
K3PO4 (1)
K3PO4 (1)
CuI (100)
CuI (20)
CuI (20)
CuI (20)
CuI (20)
CuI (20)
CuI (30)
CuI (20)
CuI (20)
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
5
74
45
54
Trace
77 (52)[c]
Trace
44
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34
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CuI (20)
n.r
Trace
Cu(OTf)2 (20)
CuCl (20)
Cu(acac)2 (20)
CuI (20)
CuI (20)
CuI (20)
65
n.r
67[d]
34[e]
n.r[f]
84[g]
CuI (20)
[a] Reaction conditions: Diphenyliodonium salts (0.1 mmol), hydantoin 1a (0.1 mmol), base and copper sources were added into a Schlenk tube under N2
atmosphere. Anhydrous and degassed toluene (0.5 mL) was added to it and mixture was stirred at specified temperature. Anhydrous DCE was used (2 mL).
[b] H NMR yield. [c] CuI (10 mol%). [d] Ph2IBF4 (1 equiv.). [e] Ph2IBr (1 equiv.). [f] Ph2IOTs (1 equiv.). [g] 2a (1.2 equiv.).
1
bases were screened to optimize the reaction conditions and
surprisingly, in the presence of K3PO4, complete consumption of
starting compounds was observed while maintaining the higher
product yield (entry 5) in shorter reaction time. With two
equivalents of base (K3PO4) and longer reaction time (entry 6),
we observed mostly decomposition of 2a with a trace amount
of product formation. Further optimization for base and solvent
was examined but, the yield of the reaction did not improve
and other side products were monitored (entries 7–10). In
toluene, a lower yield of the desired product was observed
(entry 7). CuI and CuII catalysts such as Cu(OTf)2, Cu(acac)2, CuCl
etc. were evaluated, but CuI was found to be the superior
catalyst (entries 11–13). Finally, the impact of the anion in
iodonium salts was optimized; where tetraflouroborate salt
showed better yield in comparison to other salts (entries 14–
16).
Since different synthetic routes to iodonium salts ease the
incorporation of different structure and aryl groups, other
anions (OTs, PF6, TFA, Br) were also investigated but, decom-
position of the iodonium salt was observed with these anions
containing iodonium salts. In the case of À OTs iodonium salt, O-
arylation at the tosyl group was primarily observed which is
opposite to Sandtorv’s result.[20] Nevertheless, O-arylation is
possible with À OTs,[21] but À OTs acts as a good counter anion
depending on the reaction conditions both in metal-free and
metal-catalyzed reactions.[20,22] Our Cu-catalysed version of N-
arylation of hydantoins was achieved because of the lesser
nucleophilicity of the diaryliodonium triflate.
electron-donating and electron-withdrawing groups.[23] Sym-
metrical iodonium salts could be easily synthesized from direct
arenes or aryl iodides and when approached by O-, N- and C-
nucleophiles, one of the aryl groups got involved in the
subsequent arylation. But, in most cases of unsymmetrical
diaryliodonium salts, one aryl part is electron-withdrawing and
the other is electron-donating and also bears ortho-substituted
groups like mesityl or triisopropylphenyl; around the hyper-
valent iodine center. This brings the chemoselectivity factor
between the aryl groups. Good atom economy of the reaction
can be considered only when one aryl group exclusively takes
part in arylation and the other aryl group leaves as “dummy”
iodoarene.
The chemoselectivity study (Scheme 2) was performed
under optimized reaction conditions between hydantoin (1a)
and four selected iodonium salts (2l, 2s, 2t, and 2u). A mixture
of products was observed in the case of 2t and the electron-
deficient group was found to get transferred to furnish 4a, as
the major product. In comparison to p-anisyl as dummy ligand,
mesityl containing iodonium salts showed higher selectivity in
both the cases (2l and 2s). The observed trend is matching
with previous studies under metal-catalyzed conditions which
implies “mesityl” as a dummy group is more reliable due to
steric factor.[24]
Having the chemoselectivity study in hand, the scope of the
reaction was first examined for the arylation of hydantoins with
iodonium salts (2a) (Scheme 3). Simple hydantoin (1b) was
arylated selectively at N3-position without showing any traces of
by-product(s). The presence of one α-hydrogen in compounds
(3a–3f) did not hinder the selective arylation at N3-position of
Chemoselective pattern study of the reaction is very
interesting with a range of iodonium salts having both
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with the yield of 84% and 87% respectively. Bulky hydantoins
(3g) also tolerated the reaction condition and showed arylation
in a similar pattern.
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Next, the scope of the Cu-catalysed N3-arylation of hydan-
toins was studied (Scheme 4). Various symmetrical and unsym-
metrical iodonium salts were employed as a coupling partner.
The use of 5,5-dimethylhydantoin (1a) and diaryliodonium salts
containing electron-donating, electron-withdrawing, and elec-
tron-neutral groups afforded the desired products (4a–4q) in
moderate to good yields. Halide substituents such as À F, À Cl,
and À Br were easily transferred from its corresponding sym-
metrical iodonium salts and products 4c, 4f, and 4p were
obtained in good yields in less than 10 hrs, which is a rather
difficult to accomplish in metal-catalyzed reactions with other
aryl sources.[25] Ortho-substituted groups such as mesityl, À Me
and À CO2Me were found to be well tolerated under this
protocol and furnished the products 4d, 4k, and 4m. As found
in the chemoselectivity study, electron-withdrawing groups
such as À NO2, À CF3, À CO2Me, and -CN were selectively trans-
ferred to the hydantoin core affording 4e, 4l, 4m, and 4o
respectively with moderate yields. Similarly, tert-butyl salt, 4g
underwent arylation at room temperature, though it took a
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Scheme 2. Chemoselectivity trend. Yields are based on 1H NMR using DMF
as internal standard.
Scheme 3. Scope of Hydantoins. Reaction conditions: 3-aryl-5,5-dimeth-
ylhydantoin (0.25 mmol), iodonium salt (0.3 mmol), CuI (20 mol%) and K3PO4
(0.25 mmol) in DCE (0.1 M). [a] 2 equiv. of 2a. [b] 2 equiv. of 1b. Isolated
yields.
these hydantoins without showing any mixture of C5- and N1-
arylation. Alanine-derived hydantoin, 3b was less reactive than
other bulky amino acid-derived hydantoins (3c and 3d). Nitro-
phenylation of leucine-derived hydantoin 3e also showed good
conversion (75% isolated yield) and we successfully observed
regioselective arylation. D-valine (3d) and L-phenylalanine-
derived hydantoin (3f) reacted without affecting the chirality
Scheme 4. Scope of diaryliodonium salts. Reaction conditions: 5,5-dimeth-
ylhydantoin (0.25 mmol), iodonium salt (0.3 mmol), CuI (20 mol%), K3PO4
°
(0.25 mmol), DCE (0.1 M). [a] 2 equiv. of iodonium salt. [b] 80 C. Isolated
yields.
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longer time for the completion of the reaction. Very few reports
(ESI, Table S10), but the yield of the reaction was low with DCE
as the solvent. Temperature and solvents were screened again
for the reaction between N3-phenyl-5,5-dimethylhydantoin and
diphenyliodonium triflate, while maintaining the other parame-
ters. It was observed that 1,4-dioxane was the solvent of choice
at room temperature, and gratifyingly, the yield of 5a increased
to 82%. Other CuI and CuII sources and different bases were
tested, but the yield did not improve. The synthesis of all the
N1,N3-arylated compounds (5a–5j) proceeded smoothly under
the optimized condition in moderate to good yields. Sym-
metrical iodonium salts containing electron-neutral and elec-
tron-donating and unsymmetrical iodonium salts containing
electron-deficient groups were easily tolerated under the
reaction conditions. Hereby, we have demonstrated substrate
scopes on both the nitrogen atoms of the hydantoin motif.
The protocol was extended successfully to a larger scale
(Scheme 6) for 4a and 4e showcasing the gram-scale applic-
ability of this method.
Aiming the mechanistic study (Scheme 7), the reaction was
performed in the presence of 2 equiv. of TEMPO (2,2,6,6-
tetramethylpiperidine-1-oxyl) as a radical scavenger. But, the N3-
arylated product was obtained in 65% yield which indicates
that radicals are not involved.[27] The plausible mechanism of
this simple and robust N-arylation starts with the reaction
between the copper(I) catalyst and the diaryliodonium salt.
PhÀ Cu(III) species A, a highly electrophilic copper centre is
generated after the oxidative addition of iodonium salts to CuI.
The N3 atom of the hydantoin undergoes coordination with
species A and forms species B, from which reductive elimination
delivers the arylated product while making the copper source
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are found on the transfer of electron-donating groups to
hydantoins in metal-catalyzed reaction with aryl halides; but, in
our protocol a p-methoxyphenyl group, 4h is easily used as the
arylating partner from bis-(4-methoxyphenyl)iodonium salt, in
74% yield. Biphenyl group from (biphenyl)mesityl iodonium salt
was also selectively induced in the hydantoin core, 4i with
excellent yields. 4n and 4j are the examples for meta-
substituted hydantoins from bis-(3-methylphentyl)iodonium
tertrafluoroborate (2k) and mesityl-(3-nitrolphenyl)iodonium
triflate (2o) respectively. Heterocyclic moiety containing iodo-
nium salts were also employed in this protocol and pyridine
ring containing 4q was isolated despite the formation of 4d as
the side product.
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N1-Arylation of hydantoins with diaryliodonium salts
After the comprehensive study on N3-arylation of hydantoins,
we next focused on a more challenging aspect, i.e. arylation of
the remaining nitrogen, i.e. N1.[26] We initially attempted one-
pot double arylations from the single iodonium salt by utilizing
the eliminated aryl iodide. Temperature and base for the
reaction were screened in order to achieve N1-arylation, but the
reaction didn’t proceed beyond N3-arylation (ESI, Table S9). The
same reaction conditions were imposed in a step-wise manner
using the N3-arylated product for the N1-arylation (Scheme 5)
Scheme 6. Larger-scale synthesis.
Scheme 5. Synthesis of N1,N3-diaryl-hydantoin. Reaction conditions: 3-aryl-
5,5-dimethylhydantoin (0.25 mmol), iodonium salt (0.3 mmol), CuI (20 mol%)
and K3PO4 (0.25 mmol) in DCE (0.1 M). Isolated yields.
Scheme 7. Plausible Mechanism.
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available for the next cycle. The mechanism for the arylation of
General procedure A: N3-arylation of hydantoins
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the N1-position can also be proposed in the same line. This
similar pattern of mechanism has also been proposed in the
literature.[28]
To an oven-dried Schlenck-tube, hydantoin 1 (0.25 mmol), diary-
liodonium salt 2 (0.3 mmol), CuI (50 μmol, 0.2 equiv.) and K3PO4
(0.25 mmol) was added under N2 atmosphere. The tube was sealed
and DCE (3 mL) was added under N2 atmosphere. The reaction
mixture was stirred at room temperature for the indicated time.
The reaction was filtered through celite and concentrated in vacuo.
The crude product was purified as described.
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Conclusion
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3-phenylimidazolidine-2,4-dione (3a)[32] Synthesized following gen-
In conclusion, we have developed a mild and robust Cu-
catalyzed N-arylation of hydantoins at room temperature with
diaryliodonium salts. Broad substrate scopes of hydantoins
were discussed for N3-arylation including chiral hydantoins. Our
protocol showed moderate to good yields for the formation of
simple to congested hydantoins. Electron-neutral, electron-
donating and electron-withdrawing groups from both sym-
metrical and unsymmetrical iodonium salts were well tolerated.
Ortho-substituted arylating partners were also employed and
successful transformation with moderate yields was achieved.
Our methodology was also extended to N1-arylation and
substantial scopes of diaryliodonium salts were discussed. We
believe this methodology could be of interest to organic
chemists and affords many medicinally active scaffolds.
eral procedure
A starting from imidazolidine-2,4-dione (1b)
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(25 mg, 0.25 mmol, 1 equiv.), diphenyliodonium triflate (2a)
(129 mg, 0.3 mmol, 1.2 equiv.), CuI (9.5 mg, 0.05 mmol, 0.2 equiv.)
and K3PO4 (53 mg, 0.25 mmol). The reaction mixture was stirred at
room temperature for 10 h. The mixture was purified by column
chromatography (AcOEt/Hexane: 5/95 followed by 40/60) to afford
3a (33 mg, 0.187 mmol, 75%) as white solid. Rf 0.45 (AcOEt
/Hexane: 40/60). M.p. 191–192 C (lit. 194 C); 1H NMR (400 MHz,
Chloroform-d): δ 7.51–7.49 (m, 2H, ArH), 7.41–7.38 (m, 3H, ArH), 4.07
(s, 2H, methylene); 13C NMR (100 MHz, Chloroform-d): δ 170.3, 157.8,
131.3, 129.0, 128.4, 126.0, 46.2; IR (νmax, cmÀ 1): 3173 (b), 3056 (m),
2932 (s), 1835 (s), 1744 (s), 1595 (s), 1503 (s), 1449 (s), 1405 (s).
HRMS (ESI) m/z: [M+H]+ calcd for C9H8N2O2 177.0659; found
177.0688.
°
°
5-methyl-3-phenylimidazolidine-2,4-dione (3b)[33] Synthesized fol-
lowing general procedure A starting from 5-methylimidazolidine-
2,4-dione (1c) (29 mg, 0.25 mmol) and diphenyliodonium triflate
(2a) (129 mg, 0.3 mmol). The reaction was stirred for 12 h. The
reaction mixture was purified by column chromatography (AcOEt/
Hexane: 5/95 followed by 20/80) to afford 3b (41 mg, 0.215 mmol,
Experimental Section
All reactions were performed in oven-dried Schlenk-tubes or round
bottom flasks under nitrogen condition unless otherwise stated.
Dichloromethane (DCM), dichloroethane (DCE), and acetonitrile
(ACN) were dried by refluxing over CaH2 under nitrogen condition
and stored over 4 Å molecular sieves. Toluene and 1,4-dioxane
were dried utilizing conventional drying procedures using sodium/
benzophenone as an indicator and stored over 4 Å molecular
sieves. All chemicals were purchased from commercial suppliers
and used as received unless otherwise stated. NaOH, Cs2CO3, K3PO4,
and tBuOK were stored in a desiccator. For experimental details, see
the reference for each method used. m-CPBA (Aldrich, 77% active
oxidant) was dried at room temperature over high vacuum for
1 hour and titrated by iodometric titration[29] prior to use in the
synthesis of diaryliodonium salts. Thin Layer Chromatography (TLC)
analysis was performed on pre-coated Merck silica gel 60 F254 plates
using UV (254 nm) light and/or with KMnO4-stain. Column
chromatography was performed on 100–200 mesh silica gel using
the gradient system, freshly distilled ethyl acetate-hexane mixture.
All NMR data were recorded at 400 MHz at 298 K using CDCl3 and
DMSO-d6 as solvents. Chemical shifts are given in ppm relative to
the residual solvent peak (1H NMR: CDCl3 δ 7.26 and sometimes δ
1.56 (CDCl3-water) and in DMSO-d6 δ 2.50 and δ 3.3 (DMSO-water);
13C NMR: CDCl3 δ 77.16, DMSO-d6 δ 39.52) with multiplicity (br=
broad, s=singlet, d=doublet, t=triplet, q=quartet, quin=quin-
tet, sex=sextet, sep=septet, m=multiplet, app=apparent), cou-
pling constants (in Hz) and integration. Chemical shifts for 19F-NMR
are given in ppm relative to monofluorobenzene (À 113.15 ppm)
used as internal standard. The raw data of NMR were processed by
MestReNova software.
86%) as a off-white solid. Rf 0.35 (AcOEt /Hexane: 40/60). M.p. 146–
1
°
°
148 C (lit. 151 C); H NMR (400 MHz, Chloroform-d): δ 7.50–7.47 (m,
2H, ArH), 7.41–7.37 (m, 3H, ArH), 6.58 (br s, 1H, amide), 4.22 (qd, J=
6.9, 1.3 Hz, 1H, methine), 1.52 (d, J=8 Hz, 3H, methyl); 13C NMR
(100 MHz, Chloroform-d): δ 173.1, 156.2, 131.5, 129.1, 128.3, 126.1,
52.3, 17.4; IR (νmax, cmÀ 1): 3216 (b), 3080 (b), 3311 (m), 1780 (s), 1720
(s), 1404 (s), 1377 (s), 1240 (s), 1041 (s), 916 (s) 818 (s), 639 (s); HRMS
(ESI) m/z: [M+H]+ calcd for C10H10N2O2 191.0815; found 191.0866.
5-isobutyl-3-phenylimidazolidine-2,4-dione (3c) Synthesized follow-
ing general procedure A starting from 5-isobutylimidazolidine-2,4-
dione (1d) (39 mg, 0.25 mmol) and diphenyliodonium triflate (2a)
(129 mg, 0.3 mmol). The reaction was stirred for 12 h. The reaction
mixture was purified by column chromatography (AcOEt/Hexane:
5/95 followed by 40/60) to afford 3c (47 mg, 0.202 mmol, 81%) as a
white solid. Rf 0.42 (AcOEt /Hexane: 40/60). M.p. 174–176 C; 1H
°
NMR (400 MHz, Chloroform-d): δ 7.49–7.45 (m, 2H, ArH), 7.41–7.36
(m, 3H, ArH), 6.49 (br s, 1H, amide NH), 4.20–4.17 (m, 1H, methine),
1.92–1.82 (m, 2H, methylene), 1.69–1.64 (m, 1H, methine), 1.01–0.98
(m, 6H, methyl); 13C NMR (100 MHz, Chloroform-d): δ 173.1, 156.2,
131.5, 129.1, 128.3, 126.1, 52.3, 17.4; IR (νmax, cmÀ 1): 3255 (b), 3112
(m), 3311 (m), 1776 (s), 1726 (s), 1430 (s), 1402 (s), 1160 (s), 860 (s),
712 (s), 648 (s); HRMS (ESI) m/z: [M+H]+ calcd for C13H16N2O2
233.1285; found 233.1294.
(S)-5-isopropyl-3-phenylimidazolidine-2,4-dione (3d) Synthesized
following general procedure A starting from 5-isopropylimidazoli-
dine-2,4-dione (1e) (36 mg, 0.25 mmol) and diphenyliodonium
triflate (2a) (129 mg, 0.3 mmol). The reaction was stirred for 12 h.
The reaction mixture was purified by column chromatography
(AcOEt/Hexane: 5/95 followed by 40/60) to afford 3d (47 mg,
5,5’-dimethylhydantoin (1a) is commercially available and others
(1b–1g) are known compounds and were prepared by literature
procedures.[30] The diaryliodonium salts (2a–2u) were synthesized
according to literature procedures (see ESI).[31]
0.202 mmol, 81%) as an off-white solid. Rf 0.4 (AcOEt /Hexane:
1
°
40/60). M.p. 136–138 C; H NMR (400 MHz, Chloroform-d): δ 7.50–
7.46 (m, 2H, ArH), 7.40–7.37 (m, 3H, ArH), 6.69 (br s, 1H, amide NH)
4.06–4.07 (m, 1H, methine), 2.37–2.29 (m, 1H, methine), 1.09 (d, J=
7 Hz, 3H, methyl), 1.01 (d, J=7 Hz, 3H, methyl); 13C NMR (100 MHz,
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Chloroform-d): δ 172.6, 157.4, 131.1, 129.3, 127.9, 126.1, 62.1, 30.4,
5,5-dimethyl-3-(p–tolyl)imidazolidine-2,4-dione (4b) Synthesized
following general procedure A starting from 5,5-dimethylhydantoin
(1a) (32 mg, 0.25 mmol) and bis(4-methylphenyl)iodonium triflate
(2c) (138 mg, 0.30 mmol). The reaction was stirred for 7 h. The
reaction mixture was purified by column chromatography (AcOEt/
Hexane: 5/95 followed by 20/80) to afford 4b (49 mg, 0.225 mmol,
92%) as a light yellow solid. Rf 0.4 (AcOEt /Hexane: 40/60). M.p.
1
2
3
4
5
6
7
8
9
18.2, 15.6; IR (νmax, cmÀ 1): 3273 (b), 3116 (m), 3311 (m), 2966 (s),
1720 (s), 1429 (s), 1171 (s), 762 (s), 633 (s); HRMS (ESI) m/z: [M+H]+
calcd for C12H13N3O4 219.1128; found 219.1181.
5-isobutyl-3-(4-nitrophenyl)imidazolidine-2,4-dione (3e) Synthe-
sized following general procedure A starting from 5-isobutylimida-
zolidine-2,4-dione (1d) (39 mg, 0.25 mmol) and (4-nitrophenyl)
(2,4,6-trimethylphenyl)iodonium triflate (2l) (155 mg, 0.30 mmol).
The reaction was stirred for 12 h. The reaction mixture was purified
by column chromatography (AcOEt/Hexane: 5/95 followed by
40/60) to afford 3e (51 mg, 0.187 mmol, 75%) as a white solid. Rf
168–170 C; 1H NMR (400 MHz, Chloroform-d): δ 7.19 (s, 4H, ArH),
°
2.30 (s, 3H, methyl), 1.42 (s, 6H, methyl); 13C NMR (100 MHz,
Chloroform-d): δ 176.7, 156.4, 138.5, 129.9, 129.1, 126.1, 58.9, 25,1,
21.3; IR (νmax, cmÀ 1): 3217 (b), 2911 (m), 1720 (s), 1421 (s), 1387 (s),
1260 (s), 818 (s), 792 (s); HRMS (ESI) m/z: [M+H]+ calcd for
C12H14N2O2 219.1128; found 219.1159.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
0.35 (AcOEt /Hexane: 40/60). M.p. 155–157 C; 1H NMR (400 MHz,
°
DMSO-d6): δ 8.81 (br s, 1H, amide), 8.34 (d, J=8 Hz, 2H, ArH), 7.73
(d, J=8 Hz, 2 h, ArH), 4.27 (t, J=4 Hz, 1H, methine), 1.90–1.82 (m,
1H, methine), 1.64–1.58 (m, 2H, methylene), 0.93 (d, J=7 Hz, 6H,
methyl); 13C NMR (100 MHz, DMSO-d6): δ 173.6, 155.3, 146.2, 138.1,
127.2, 124.5, 55.1, 24.6, 23.2, 21.3; IR (νmax, cmÀ 1): 3258 (b), 2955 (s),
2840 (s), 1756 (s), 1540 (s), 1310 (s), 1135 (s), 848 (s), 768 (s), 667 (s);
HRMS (ESI) m/z: [M+H]+ calcd for C13H16N2O2 278.1135; found
279.1141.
3-(4-bromophenyl)-5,5-dimethylimidazolidine-2,4-dione (4c) Syn-
thesized following general procedure A starting from 5,5-dimeth-
ylhydantoin (1a) (32 mg, 0.25 mmol) and bis(4-bromophenyl)
iodonium triflate (2c) (176 mg, 0.30 mmol). The reaction was stirred
for 12 h. The reaction mixture was purified by column chromatog-
raphy (AcOEt/Hexane: 5/95 followed by 20/80) to afford 4c (53 mg,
0.187 mmol, 75%) as a brown solid. Rf 0.45 (AcOEt /Hexane: 40/60).
M.p. 158–161 C; 1H NMR (400 MHz, Chloroform-d): δ 7.52 (d, J=
°
(R)-5-benzyl-3-phenylimidazolidine-2,4-dione (3f) Synthesized fol-
lowing general procedure A starting from (R)-5-benzylimidazoli-
dine-2,4-dione (1e) (47 mg, 0.25 mmol) and diphenyliodonium
triflate (2a) (129 mg, 0.3 mmol). The reaction was stirred for 12 h.
The reaction mixture was purified by column chromatography
(AcOEt/Hexane: 5/95 followed by 40/60) to afford 3f (57 mg,
8 Hz, 2H, ArH), 7.26 (d, J=8 Hz, 2H, ArH), 6.82 (s, 1H, amide NH),
1.44 (s, 6H, methyl); 13C NMR (100 MHz, Chloroform-d): δ 176.1,
155.6, 132.5, 130.8, 128.1, 122.3, 58.6, 25.1; IR (νmax, cmÀ 1): 3241 (b),
3110 (m), 2089 (m), 2929 (s), 1706 (m), 1492 (s), 1427 (s), 821 (m),
732 (m), 604 (m); HRMS (ESI) m/z: [M+H]+ calcd for C11H11N2O2Br
283.0077; found 283.0091.
0.214 mmol, 87%) as a white solid. Rf 0.35 (AcOEt /Hexane: 40/60).
1
°
M.p. 126 C; H NMR (400 MHz, Chloroform-d): δ 7.46–7.42 (m, 2H,
3-mesityl-5,5-dimethylimidazolidine-2,4-dione (4d) Synthesized fol-
lowing general procedure A starting from 5,5-dimethylhydantoin
(1a) (32 mg, 0.25 mmol) and bis(2,4,6-trimethylphenyl))iodonium
triflate (2h) (154 mg, 0.30 mmol). The reaction was stirred for 16 h.
The reaction mixture was purified by column chromatography
(AcOEt/Hexane: 5/95 followed by 20/80) to afford 4d (33.21 mg,
0.135 mmol, 54%) as a white solid. Rf 0.56 (AcOEt /Hexane: 40/60).
ArH), 7.38–7.31 (m, 2H, ArH), 7.26–7.22 (m, 2H, ArH), 5.81 (br s, 1H,
amide), 4.22 (app. qd, J=7 and 1.3 Hz, 1H, methine), 3.33 (dd, J=7
and 1.3 Hz, 1H, methylene), 3.03 (dd, J=7 and 1.3 Hz, 1H, meth-
ylene); 13C NMR (100 MHz, Chloroform-d6): δ 171.7, 155.8, 134.7, 131,
129.4, 129.0, 128.8, 128.3, 127.5, 126.2, 57.7, 37.7; IR (νmax, cmÀ 1):
3205 (b), 3110 (m), 2944 (m), 1743 (s), 1402 (s), 1317 (s), 1139 (s),
746 (s); HRMS (ESI) m/z: [M+H]+ calcd for C16H14N2O2 267.1128;
found 267.1134.
M.p. 147–150 C; 1H NMR (400 MHz, Chloroform-d): δ 6.97 (s, 2H,
°
ArH), 6.80 (s, 1H, amide NH), 2.30 (s, 3H, methyl), 2.14 (s, 6H, methyl)
1.44 (s, 6H, methyl); 13C NMR (100 MHz, Chloroform-d): δ 176.2,
155.5, 139.2, 136.5, 129.1, 126.4, 59.4, 25.5, 21.1, 17.4; IR (νmax, cmÀ 1):
3227 (b), 3106 (m), 2918 (s), 2860 (s), 1746 (s), 1724 (s), 1603 (s),
1468 (m), 1283 (s), 1253 (s), 835 (m), 674 (s); HRMS (ESI) m/z: [M+
H]+ calcd for C14H18N2O2 247.1441; found 247.1475.
3,5,5-triphenylimidazolidine-2,4-dione (3g) [CAS: 52461–02-6][33]
Synthesized following general procedure A starting from 5,5-
diphenylimidazolidine-2,4-dione (1f) (63 mg, 0.25 mmol) and diphe-
nyliodonium triflate (2a) (129 mg, 0.3 mmol). The reaction was
stirred for 12 h. The reaction mixture was purified by column
chromatography (AcOEt/Hexane: 5/95 followed by 30/70) to afford
3g (59 mg, 0.182 mmol, 73%) as a white solid. Rf 0.48 (AcOEt
5,5-dimethyl-3-(4-nitrophenyl)imidazolidine-2,4-dione (4e)[14] Syn-
thesized following general procedure A starting from 5,5-dimeth-
ylhydantoin (1a) (32 mg, 0.25 mmol) and (4-nitrophenyl)(2,4,6-
trimethylphenyl)iodonium triflate (2l) (155 mg, 0.30 mmol). The
reaction was stirred for 12 h. The reaction mixture was purified by
column chromatography (AcOEt/Hexane: 10/90 followed by 30/70)
to afford 4e (43 mg, 0.172 mmol, 68%) as a white solid. Rf 0.3
/Hexane: 40/60). M.p. 208–210 C (lit. 206–207 C); 1H NMR
(400 MHz, Chloroform-d): δ 7.50–7.42 (m, 15H, ArH), 6.83 (br s, 1H,
amide); 13C NMR (100 MHz, Chloroform-d6): δ 172.2, 155.8, 139.1,
131.4, 129.1, 127.1, 126.3, 70.07; IR (νmax, cmÀ 1): 3237 (b), 3105 (m),
3311 (m), 2931 (m), 1715 (s), 1431 (s), 1350 (s), 1169 (s), 689 (s);
HRMS (ESI) m/z: [M+H]+ calcd for C21H16N2O2 329.1285; found
329.1295.
°
°
(AcOEt /Hexane: 40/60). M.p. 162–164 C (lit. 168 C); 1H NMR
(400 MHz, Chloroform-d): δ 8.33 (d, J=8 Hz 2H, ArH), 7.77 (d, J=
8 Hz, 2H, ArH), 6.00 (s, 1H, amide NH), 1.58 (s, 6H, methyl); 13C NMR
(100 MHz, Chloroform-d): δ 175.3, 154.2, 146.4, 137.6, 125.6, 124.2,
58.6, 25.0; IR (νmax, cmÀ 1): 3261 (b), 2920 (s), 2852 (s), 1731 (s), 1521
(s), 1337 (s), 1135 (s), 831 (s), 725 (s); HRMS (ESI) m/z: [M+H]+ calcd
for C11H11N3O4 250.0822; found 250.0847.
°
°
5,5-Dimethyl-3-phenylhydantoin (4a)[34] Synthesized following gen-
eral procedure A starting from 5,5-dimethylhydantoin (1a) (32 mg,
0.25 mmol, 1 equiv.), diphenyliodonium triflate (2a) (129 mg,
0.3 mmol, 1.2 equiv.), CuI (9.5 mg, 0.05 mmol, 0.2 equiv.) and K3PO4
(53 mg, 0.25 mmol). The reaction mixture was stirred at room
temperature for 5 h. The crude was purified by column chromatog-
raphy (AcOEt/Hexane: 5/95 followed by 30/70) to afford 4a (42 mg,
3-(4-chlorophenyl)-5,5-dimethylimidazolidine-2,4-dione (4f) Synthe-
sized following general procedure A starting from 5,5-dimeth-
ylhydantoin (1a) (32 mg, 0.25 mmol) and bis(4-chlorophenyl)iodo-
nium triflate (2e) (149.7 mg, 0.30 mmol). The reaction was stirred
for 6 h. The reaction mixture was purified by column chromatog-
raphy (AcOEt/Hexane: 5/95 followed by 20/80) to afford 4f (49 mg,
0.205 mmol, 81%) as white solid. Rf 0.4 (AcOEt /Hexane: 40/60).
1
°
°
M.p. 162–165 C (lit. 164–167 C); H NMR (400 MHz, Chloroform-d):
δ 7.42–7.38 (m, 2H, ArH), 7.34–7.28 (m, 3H, ArH), 1.43 (s, 6H, methyl);
13C NMR (100 MHz, Chloroform-d): δ 176.4, 155.7, 131.5, 128.6,
127.9, 126.1, 58.3, 25.12; IR (νmax, cmÀ 1): 3217 (b), 3101 (s), 1728 (s),
1427 (s), 1295 (s), 1148 (s), 861 (s), 765 (m), 708 (s), 604 (s); HRMS
(ESI) m/z: [M+H]+ calcd for C11H12N2O2 205.0972; found 209.0998.
0.205 mmol, 83%) as a brownish solid. Rf 0.45 (AcOEt /Hexane:
1
°
40/60). M.p. 152–154 C; H NMR (400 MHz, Chloroform-d): δ 7.45–
7.38 (m, 4H, ArH), 6.19 (s, 1H, amide NH), 1.54 (s, 6H, methyl); 13C
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NMR (100 MHz, Chloroform-d): δ 176.5, 155.7, 139.2, 134.7, 130.4,
5,5-dimethyl-3-(o–tolyl)imidazolidine-2,4-dione (4k) Synthesized
following general procedure A starting from 5,5-dimethylhydantoin
(1a) (32 mg, 0.25 mmol) and bis(2-methylphenyl)iodonium tetra-
fluoroborate (2j) (118 mg, 0.30 mmol). The reaction was stirred for
12 h. The reaction mixture was purified by column chromatography
(AcOEt/Hexane: 5/95 followed by 30/70) to afford 4k (28 mg,
1
2
3
4
5
6
7
8
9
129.6, 127.7, 58.8, 25.4; IR (νmax, cmÀ 1): 3298 (s), 2915 (s), 2849 (s),
1715 (s), 1497 (s), 1426 (s), 1309 (s), 1148 (s), 1089 (s), 819 (s), 740
(s); HRMS (ESI) m/z: [M+H]+ calcd for C11H11N2O2Cl 239.0589; found
239.0591.
3-(4-(tert-butyl)phenyl)-5,5-dimethylimidazolidine-2,4-dione (4g)[14]
Synthesized following general procedure A starting from 5,5-
dimethylhydantoin (1a) (32 mg, 0.25 mmol) and bis(4-tert-butyl-
phenyl)iodonium triflate (2g) (162.72 mg, 0.30 mmol). The reaction
was stirred for 24 h. The reaction mixture was purified by column
chromatography (AcOEt/Hexane: 5/95 followed by 20/70) to afford
4g (46 mg, 0.177 mmol, 71%) as a brownish solid. Rf 0.43 (AcOEt
0.128 mmol, 51%) as a pink solid. Rf 0.46 (AcOEt /Hexane: 40/60).
1
°
M.p. 166–168 C; H NMR (400 MHz, Chloroform-d): δ 7.37–7.26 (m,
4H, ArH), 7.17 (d, J=8 Hz, 1H, ArH), 6.57 (s, 1H, amide NH), 2.21 (s,
3H, methyl), 1.53 (s, 6H, methyl); 13C NMR (100 MHz, Chloroform-d):
δ 176.3, 154, 148.1, 133.8, 133.4, 130.5, 122.8, 121.7, 58.1, 24.6; IR
(νmax, cmÀ 1): 3205 (b), 2943 (m), 1744 (s), 1440 (s), 1345 (s), 1225 (s),
867 (s), 765 (s); HRMS (ESI) m/z: [M+H]+ calcd for C12H14N2O2
219.1128; found 219.1154.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
/Hexane: 40/60). M.p. 173–175 C (lit. 177 C); 1H NMR (400 MHz,
Chloroform-d): δ 7.48 (d, J=8 Hz, 2H, ArH), 7.32 (d, J=8 Hz, 2H,
ArH), 6.71 (s, 1H, amide NH), 1.51 (s, 6H, methyl), 1.33 (s, 9H, tert-
butyl); 13C NMR (100 MHz, Chloroform-d): δ 176.1, 156.1, 151.2,
128.5, 126.0, 58.3, 34.7, 30.9, 25.1; IR (νmax, cmÀ 1): 3277 (s), 2972 (s),
1717 (s), 1528 (s), 1420 (s), 1141 (s), 846 (s); HRMS (ESI) m/z: [M+
H]+ calcd for C15H20N2O2 261.1598; found 261.1635.
°
°
5,5-dimethyl-3-(4-(trifluoromethyl)phenyl)imidazolidine-2,4-dione
(4l)[14] Synthesized following general procedure A starting from
5,5-dimethylhydantoin (1a) (32 mg, 0.25 mmol) and mesityl(4-
trifluoromethylphenyl)iodonium triflate (2n) (162 mg, 0.30 mmol).
The reaction was stirred for 16 h. The reaction mixture was purified
by column chromatography (AcOEt/Hexane: 10/90 followed by
3-(4-methoxyphenyl)-5,5-dimethylimidazolidine-2,4-dione (4h) Syn-
thesized following general procedure A starting from 5,5-dimeth-
ylhydantoin (1a) (32 mg, 0.25 mmol) and bis(4-methoxyphenyl)
iodonium triflate (2i) (147.06 mg, 0.30 mmol). The reaction was
stirred for 8 h. The reaction mixture was purified by column
chromatography (AcOEt/Hexane: 5/95 followed by 20/80) to afford
30/80) to afford 4k (54 mg, 0.212 mmol, 77%) as a white solid. Rf
1
°
°
0.35 (AcOEt /Hexane: 40/60). M.p. 174–176 C (lit. 179 C); H NMR
(400 MHz, Chloroform-d): δ 7.49 (d, J=8 Hz, 2H, ArH), 7.30 (d, J=
8 Hz 2H, ArH), 6.57 (s, 1H, amide NH), 1.53 (s, 6H, methyl); 13C NMR
(100 MHz, Chloroform-d): δ 176, 154.8, 148.8, 130.1, 127.5, 121.7,
121.6, 58.7, 25.3; 19F (376 MHz, Chloroform-d): δ À 57.4; IR (νmax
,
4h (44 mg, 0.185 mmol, 74%) as a white solid. Rf 0.35 (AcOEt
cmÀ 1): 3217 (b), 2949 (m), 2377 (m), 1743 (s), 1739 (s), 1408 (s), 1332
(s), 1164 (s), 1121 (s), 1038 (s), 843 (s), 713 (s); HRMS (ESI) m/z: [M+
H]+ calcd for C12H14N2O2 273.0845; found 273.1756.
1
°
/Hexane: 40/60). M.p. 134–136 C; H NMR (400 MHz, Chloroform-d):
δ 7.32 (d, J=8 Hz, 2H, ArH), 6.97 (d, J=8 Hz, 2H, ArH), 6.28 (s, 1H,
amide NH), 3.28 (s, 3H, methyl), 1.55 (s, 6H, methyl); 13C NMR
(100 MHz, Chloroform-d): δ 176.5, 159.1, 155.7, 127.4, 124.0, 114.2,
58.2, 55.5, 24.8; IR (νmax, cmÀ 1): 3268 (s), 2942 (s), 1731 (s), 1707 (s)
1460 (m), 1283 (s), 1228 (s), 1086 (s), 867 (m), 741 (s), 674 (s); HRMS
(ESI) m/z: [M+H]+ calcd for C12H14N2O3 235.1077; found 235.1109.
Methyl 2-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)benzoate (4m)
Synthesized following general procedure A starting from 5,5-
dimethylhydantoin (1a) (32 mg, 0.25 mmol) and mesityl(2-(meth-
oxycarbonyl)phenyl)iodonium triflate (2p) (159 mg, 0.30 mmol).
The reaction was stirred for 12 h. The reaction mixture was purified
by column chromatography (AcOEt/Hexane: 5/95 followed by
20/80) to afford 4m (36 mg, 0.140 mmol, 56%) as a brown-coloured
liquid. Rf 0.42 (AcOEt /Hexane: 40/60). 1H NMR (400 MHz, Chloro-
form-d): δ 8.12 (d, J=8 Hz, 1H, ArH), 7.68 (dt, J=8 Hz & 1.6 Hz, 1H,
ArH), 7.53 (dt, J=8 Hz & 1.3 Hz, 1H, ArH), 7.37 (d, J=8 Hz, 1H, ArH),
6.36 (s, 1H, amide NH), 3.85 (s, 3H, methyl), 1.53 (s, 6H, methyl); 13C
NMR (100 MHz, Chloroform-d): δ 176.3, 165.1, 155.6, 133.3, 131.6,
131.5, 130.0, 129.2, 128.0, 58.7, 52.07, 25.3; IR (νmax, cmÀ 1): 3215 (b),
2918 (m), 1777 (s), 1729 (s), 1715 (s), 1434 (s), 1263 (s), 1107 (s), 710
(s), 678 (s); HRMS (ESI) m/z: [M+H]+ calcd for C13H14N2O4 263.1026;
found 263.1031.
3-([1,1’-biphenyl]-4-yl)-5,5-dimethylimidazolidine-2,4-dione (4i)[14]
Synthesized following general procedure A starting from 5,5-
dimethylhydantoin (1a) (32 mg, 0.25 mmol) and (biphenyl)(2,4,6-
trimethylphenyl)iodonium triflate (2h) (164 mg, 0.30 mmol). The
reaction was stirred for 16 h. The reaction mixture was purified by
column chromatography (AcOEt/Hexane: 10/90 followed by 30/70)
to afford 4i (58 mg, 0.205 mmol, 82%) as a white solid. Rf 0.4
(AcOEt /Hexane: 40/60). M.p. 188–190 C (lit. 185 C); 1H NMR
(400 MHz, Chloroform-d) δ 7.70 (d, J=8 Hz, 2H, ArH), 7.60 (d, J=
8 Hz, 2H, ArH), 7.52–7.44 (m, 4H, ArH), 7.38 (t, J=8 Hz, 1H, ArH),
6.75 (s, 1H, amide NH), 1.55 (s, 6H, methyl); 13C NMR (100 MHz,
Chloroform-d) δ 175.8, 155.1, 141, 139.3, 130.1, 128.4, 127.4, 126.7,
126, 58.4, 24.8; IR (νmax, cmÀ 1): 3221 (b), 2908 (s), 1755 (s), 1489 (s),
1318 (s), 1156 (s), 810 (s), 743 (s); HRMS (ESI) m/z: [M+H]+ calcd for
C17H16N2O2 281.1285; found 281.1308.
°
°
5,5-dimethyl-3-(m–tolyl)imidazolidine-2,4-dione (4n) Synthesized
following general procedure
A
starting from 5,5-dimeth-
ylhydantoin (1a) (32 mg, 0.25 mmol) and bis(m-tolyl)iodonium
tetrafluoroborate (2k) (119 mg, 0.30 mmol). The reaction was stirred
for 10 h. The reaction mixture was purified by column chromatog-
raphy (AcOEt/Hexane: 5/95 followed by 20/80) to afford 4n (42 mg,
0.195 mmol, 78%) as a white solid. Rf 0.48 (AcOEt /Hexane: 40/60).
5,5-dimethyl-3-(3-nitrophenyl)imidazolidine-2,4-dione (4j) Synthe-
sized following general procedure A starting from 5,5-dimeth-
ylhydantoin (1a) (32 mg, 0.25 mmol) and (3-nitrophenyl)(2,4,6-
trimethylphenyl)iodonium triflate (2h) (155 mg, 0.30 mmol). The
reaction was stirred for 18 h. The reaction mixture was purified by
column chromatography (AcOEt/Hexane: 10/90 followed by 40/60)
M.p. 145–147 C; 1H NMR (400 MHz, Chloroform-d): δ 7.38 (t, J=
°
8 Hz, 1H, ArH), 7.22–7.20 (m, 3H, ArH), 6.33 (s, 1H, amide NH), 2.42
(s, 3H, methyl), 1.55 (s, 6H, methyl); 13C NMR (100 MHz, Chloroform-
d): δ 176.7, 156.0, 139.4, 131.4, 129.4, 129.1, 127.2, 123.4, 58.8, 25.3,
21.4; IR (νmax, cmÀ 1): 3212 (b), 2955 (m), 1734 (s), 1438 (s), 1342 (s),
1228 (s), 865 (s), 769 (s); HRMS (ESI) m/z: [M+H]+ calcd for
C12H14N2O2 219.1128; found 219.1159.
to afford 4j (44 mg, 0.176 mmol, 72%) as a white solid. Rf 0.35
1
°
(AcOEt /Hexane: 40/60). M.p. 143–146 C; H NMR (400 MHz, DMSO-
d6): δ 8.72 (s, 1H, amide NH), 8.37 (s, 1H, ArH), 8.25 (d, J=8 Hz, 1H,
ArH), 7.87 (d, J=8 Hz, 1H, ArH), 7.75 (d, J=8 Hz, 1H, ArH), 1.43 (s,
6H, methyl); 13C NMR (100 MHz, DMSO-d6): δ 176.3, 154, 148.1,
133.8, 133.4, 130.5, 122.8, 121.7, 58.1, 24.6; IR (νmax, cmÀ 1): 3223 (b),
2933 (s), 1732 (s), 1509 (s), 1321 (s), 1176 (s), 866 (s), 790 (s); HRMS
(ESI) m/z: [M+Na]+ calcd for C11H11N3O4 250.0822; found 250.9121.
4-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)benzonitrile (4o) Synthe-
sized following general procedure A starting from 5,5-dimeth-
ylhydantoin (1a) (32 mg, 0.25 mmol) and (4-cyanophenyl)(mesityl)
iodonium triflate (2m) (149 mg, 0.30 mmol). The reaction was
stirred for 15 h. The reaction mixture was purified by column
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chromatography (AcOEt/Hexane: 10/90 followed by 20/80) to afford
128.7, 128.1, 126.1, 63.2, 23.6; IR (νmax, cmÀ 1): 2976 (s), 2929 (s), 1780
(s), 1714 (s), 1496 (s), 1412 (s), 1366 (s), 1200 (s) 878 (m), 755 (s), 692
(s); HRMS (ESI) m/z: [M+H]+ calcd for C17H16N2O2 281.1285; found
281.1352.
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4
5
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4q (43 mg, 0.1 mmol, 52%) as a white solid. Rf 0.38 (AcOEt /Hexane:
1
°
40/60). M.p. 182 C; H NMR (400 MHz, Chloroform-d): δ 7.76 (d, J=
8 Hz, 1H, ArH), 7.69 (d, J=8 Hz, 1H, ArH), 6.47 (s, 1H, amide NH),
1.56 (s, 6H, methyl); 13C NMR (100 MHz, Chloroform-d): δ 175.5,
154.4, 135.4, 132.4, 125.6, 118.2, 111.1, 58.3, 24.8; IR (νmax, cmÀ 1):
3214 (b), 2948 (s), 2270 (s), 1766 (s), 1643 (s), 1532 (s), 1406 (s), 1141
(s), 894 (s), 776 (s), 684 (s); HRMS (ESI) m/z: [M+H]+ calcd for
C12H11N3O2 230.0924; found 230.0934.
5,5-dimethyl-3-phenyl-1-(p–tolyl)hydantoin (5b) Synthesized fol-
lowing general procedure B starting from 3-phenyl-5,5-dimeth-
ylhydantoin (4a) (51 mg, 0.25 mmol) and bis(4-methylphenyl)
iodonium triflate (2c) (138 mg, 0.30 mmol). The reaction was stirred
for 12 h. The reaction mixture was purified by column chromatog-
raphy (AcOEt/Hexane: 5/95 followed by 20/80) to afford 5b (66 mg,
3-(4-fluorophenyl)-5,5-dimethylimidazolidine-2,4-dione (4p) Syn-
thesized following general procedure A starting from 5,5-dimeth-
ylhydantoin (1a) (32 mg, 0.25 mmol) and bis(4-fluorophenyl)iodo-
nium triflate (2f) (139 mg, 0.30 mmol). The reaction was stirred for
9 h. The reaction mixture was purified by column chromatography
(AcOEt/Hexane: 5/95 followed by 30/80) to afford 4p (36 mg,
0.165 mmol, 66%) as a white solid. Rf 0.38 (AcOEt /Hexane: 40/60).
0.225 mmol, 90%) as a white solid. Rf 0.52 (AcOEt /Hexane: 30/70).
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1
°
M.p. 143–145 C; H NMR (400 MHz, Chloroform-d): δ 7.50–7.44 (m,
4H, ArH), 7.35–7.33 (m, 1H, ArH), 7.26 (d, J=8 Hz, 2H, ArH), 7.19 (d,
J=8 Hz, 2H, ArH), 2.39 (s, 3H, methyl), 1.52 (s, 6H, methyl); 13C NMR
(100 MHz, Chloroform-d): δ 175.2, 154.0, 138.5, 131.8, 130.0, 128.8,
127.9, 126.4, 63.3, 23.7, 21.1; IR (νmax, cmÀ 1): 2975 (s), 2930 (s), 1779
(s), 1713 (s), 1493 (s), 1406 (s), 1198 (s), 1143, 767 (s), 687 (s), 517 (s);
HRMS (ESI) m/z: [M+H]+ calcd for C18H18N2O2 295.1441; found
295.1468.
M.p. 176–178 C; 1H NMR (400 MHz, Chloroform-d): δ 7.42–7.39
°
(app. dd, J=8 and 4 Hz, 2H, ArH), 7.16 (app. t, J=8 Hz, 2H, ArH),
6.36 (s, 1H, amide NH), 1.54 (s, 6H, methyl); 13C NMR (100 MHz,
Chloroform-d): δ 175.7, 162.4, 161.56 (d, JC-F =247 Hz), 155.2, 127.69
(d, JC-F =9 Hz), 127.15 (d, JC-F =3 Hz), 115.69 (d, JC-F =15 Hz), 58.3,
24.5; 19F (376 MHz, Chloroform-d): δ À 112.9; IR (νmax, cmÀ 1): 3218 (b),
2908 (s), 1765 (s), 1711 (s), 1530 (s), 1258 (s), 1130 (s), 884 (s), 712
(s); HRMS (ESI) m/z: [M+H]+ calcd for C11H11N2O2F 223.0877; found
223.0891.
5,5-dimethyl-1-(4-nitrophenyl)-3-phenylhydantoin (5c)[14] Synthe-
sized following general procedure B starting from 3-phenyl-5,5-
dimethylhydantoin (4a) (51 mg, 0.25 mmol) and (4-nitrophenyl)
(2,4,6-trimethylphenyl)iodonium triflate (2l) (155 mg, 0.30 mmol).
The reaction was stirred for 12 h. The reaction mixture was purified
by column chromatography (AcOEt/Hexane: 5/95 followed by
5,5-dimethyl-3-(pyridin-3-yl)imidazolidine-2,4-dione (4q) Synthe-
sized following general procedure A starting from 5,5-dimeth-
ylhydantoin (1a) (32 mg, 0.25 mmol) and mesityl(pyridin-3-yl)
iodonium triflate (2r) (141 mg, 0.30 mmol). The reaction was stirred
for 18 h. The reaction mixture was purified by column chromatog-
raphy (AcOEt/Hexane: 10/90 followed by 30/80) to afford 4p
20/80) to afford 5c (55 mg, 0.170 mmol, 68%) as a pale yellow
1
°
°
solid. Rf 0.45 (AcOEt /Hexane: 30/70). M.p. 133–135 C (lit. 131 C); H
NMR (400 MHz, Chloroform-d): δ 8.32 (d, J=8 Hz, 2H, ArH), 7.62 (d,
J=8 Hz, 2H, ArH), 7.52–7.41 (m, 5H, ArH), 1.66 (s, 6H, methyl); 13C
NMR (100 MHz, Chloroform-d): δ 174.3, 153.5, 146.2, 141.0, 131.3,
129.0, 127.4, 126.4, 124.7, 64.0, 24.5; IR (νmax, cmÀ 1): 2923 (m), 1776
(s), 1724 (s), 1522 (s), 1497 (s), 1403 (s), 1333 (s), 1194, 854 (s), 751
(s), 619 (s); HRMS (ESI) m/z: [M+H]+ calcd for C17H15N3O4 326.1135;
found 326.1175.
(29 mg, 0.165 mmol, 56%) as a white solid. Rf 0.32 (AcOEt /Hexane:
1
°
40/60). M.p. 154–157 C; H NMR (400 MHz, Chloroform-d): δ 8.79 (s,
1H, ArH), 8.62 (d, J=8 Hz, 1H, ArH), 7.84 (d, J=9.5 Hz, 1H, ArH),
7.45–7.42 (m, 1H, ArH), 6.69 (s, 1H, amide NH), 1.57 (s, 6H, methyl);
13C NMR (100 MHz, Chloroform-d): δ 175.9, 154.6, 148.9, 146.8,
133.4, 129.3, 123.5, 59.1, 25.3; IR (νmax, cmÀ 1): 3209 (b), 2920 (s), 1762
(s), 1712 (s), 1534 (s), 1354 (s), 1347 (s), 1076 (s), 862 (s); HRMS (ESI)
m/z: [M+H]+ calcd for C10H11N3O2 206.0924; found 206.0949.
1-(4-bromophenyl)-5,5-dimethyl-3-phenylhydantoin (5d) Synthe-
sized following general procedure B starting from 3-phenyl-5,5-
dimethylhydantoin (4a) (51 mg, 0.25 mmol) and bis(4-bromophen-
yl)iodonium triflate (2c) (176 mg, 0.30 mmol). The reaction was
stirred for 12 h. The reaction mixture was purified by column
chromatography (AcOEt/Hexane: 5/95 followed by 20/80) to afford
General procedure B: for N1-Arylation
5e (69 mg, 0.170 mmol, 78%) as a beige solid. Rf 0.56 (AcOEt
1
°
/Hexane: 30/70). M.p. 122–124 C; H NMR (400 MHz, Chloroform-d):
To an oven-dried Schlenck-tube, 3-arylated-hydantoin
4
δ 7.51 (d, J=8 Hz, 2H, ArH), 7.40–7.39 (app. d, J=4 Hz, 4H, ArH),
7.32–7.28 (m, 1H, ArH), 7.13 (d, J=8 Hz, 2H, ArH), 1.46 (s, 6H,
methyl); 13C NMR (100 MHz, Chloroform-d): δ 173.7, 152.5, 132.1,
(0.25 mmol), diaryliodonium salt (0.3 mmol), CuI (50 μmol,
2
0.2 equiv.) and K3PO4 (0.25 mmol) was added under N2 atmosphere.
The tube was sealed and DCE (3 mL) was added under N2
atmosphere. The reaction mixture was stirred at room temperature
for indicated time period. The reaction was filtered through celite
and concentrated in vacuo. The crude product was purified as
described.
131.8, 130.5, 129.4, 128.1, 127.2, 125.1, 121.5, 62.5, 23.0; IR (νmax
,
cmÀ 1): 2927 (s), 2856 (s), 1772 (s), 1715 (s), 1494 (s), 1416 (s), 1203
(s), 1154 (s), 1069 (s), 879 (s), 804 (s), 767 (s), 687 (s), 518 (s); HRMS
(ESI) m/z: [M+H]+ calcd for C17H15N2O2Br 359.0390; found 359.0434.
1-(4-chlorophenyl)-5,5-dimethyl-3-phenylhydantoin (5e) Synthe-
sized following general procedure B starting from 3-phenyl-5,5-
dimethylhydantoin (4a) (51 mg, 0.25 mmol) and bis(4-chlorophen-
yl)iodonium triflate (2e) (149.7 mg, 0.30 mmol). The reaction was
stirred for 12 h. The reaction mixture was purified by column
chromatography (AcOEt/Hexane: 5/95 followed by 20/80) to afford
5,5-dimethyl-1,3-diphenylhydantoin (5a)[35] To an oven-dried
Schlenck-tube, 3-phenyl-5,5-dimethylhydantoin (4a) (51 mg,
0.25 mmol, 1 equiv.), diphenyliodonium triflate (2a) (129 mg,
0.3 mmol, 1.2 equiv.), CuI (9.5 mg, 0.05 mmol, 0.2 equiv.) and K3PO4
(53 mg, 0.25 mmol) were added under N2 atmosphere. The tube
was sealed and 1,4-dioxane (3 mL) was added under N2 atmos-
phere. The reaction mixture was stirred at room temperature for
10 h. The reaction mixture was filtered through celite and
concentrated in vacuo. The crude was purified by column
chromatography (AcOEt/Hexane: 5/95 followed by 20/80) to afford
5d (63 mg, 0.2 mmol, 82%) as a white solid. Rf 0.5 (AcOEt /Hexane:
1
°
30/70). Mp: 118–120 C; H NMR (400 MHz, Chloroform-d): δ 7.57 (d,
J=8 Hz, 2H, ArH), 7.46–7.45 (app. d, J=4 Hz, 4H, ArH), 7.34–7.33 (m,
1H, ArH), 7.19 (d, J=8 Hz, 2H, ArH), 1.52 (s, 6H, methyl); 13C NMR
(100 MHz, Chloroform-d): δ 174.6, 153.6, 133, 132.7 131.4, 130.3,
130.2, 128.9, 128.1, 125.9, 122.3, 63.5, 23.7; IR (νmax, cmÀ 1): 2981 (s),
2917 (s), 1768 (s), 1707 (s), 1491 (s), 1416 (s), 1206 (s), 1150 (s), 1088
(s), 878 (s), 697 (s), 519 (s); HRMS (ESI) m/z: [M+K]+ calcd for
C17H15N2O2Cl 359.0471; found 359.0433.
5a (57 mg, 0.205 mmol, 82%) as white solid. Rf 0.5 (AcOEt /Hexane:
1
°
°
30/70). M.p. 124–126 C (lit. 130 C); H NMR (400 MHz, Chloroform-
d): δ 7.52–7.32 (m, 10H, ArH), 1.43 (s, 6H, methyl); 13C NMR
(100 MHz, Chloroform-d): δ 174.9, 153.8, 134.1, 131.9, 129.6, 129.0,
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5,5-dimethyl-3-(4-nitrophenyl)-1-phenylhydantoin (5f)[14] Synthe-
12 h. The reaction mixture was purified by column chromatography
(AcOEt/Hexane: 5/95 followed by 30/70) to afford 5j (55 mg,
0.140 mmol, 56%) as a white solid. Rf 0.56 (AcOEt /Hexane: 30/70).
1
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5
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sized following general procedure B starting from 5,5-dimethyl-3-
(4-nitrophenyl)hydantoin (4e) (62 mg, 0.25 mmol) and diphenylio-
donium triflate (2a) (129 mg, 0.3 mmol). The reaction was stirred
for 12 h. The reaction mixture was purified by column chromatog-
raphy (AcOEt/Hexane: 5/95 followed by 30/70) to afford 5f (62 mg,
0.192 mmol, 77%) as a white solid. Rf 0.45 (AcOEt /Hexane: 30/70).
1
°
M.p. 125–127 C; H NMR (400 MHz, Chloroform-d): δ 7.50–7.47 (m,
4H, ArH), 7.40–7.35 (m, 1H, ArH), 7.32–7.28 (m, 2H, ArH), 7.19–7.14
(m, 2H, ArH), 1.54 (s, 6H, methyl); 13C NMR (100 MHz, Chloroform-d):
δ 174.8, 162.4 (d, JC-F =273 Hz), 154.0, 131.7, 131.0, 129.8, 129.0,
128.1, 126.1, 116.5 (d, JC-F =3 Hz), 63.5, 23.8; 19F (376 MHz, Chloro-
form-d): δ À 112.5; IR (νmax, cmÀ 1): 2994 (m) 1788 (s), 1729 (s), 1510
(s), 1417 (s), 1214 (s), 1202 (s), 1147 (s) 691 (s); HRMS (ESI) m/z: [M+
H]+ calcd for C17H15N2O2F 299.1190; found 299.1210.
M.p. 206–208 C (lit. 213 C); 1H NMR (400 MHz, Chloroform-d): δ
8.35 (d, J=8 Hz, 2H, ArH), 7.86 (d, J=8 Hz, 2H, ArH), 7.51–7.47 (m,
3H, ArH), 7.33 (m, 2H, ArH), 1.58 (s, 6H, methyl); 13C NMR (100 MHz,
Chloroform-d): δ 173.9, 153, 146.1, 137.7, 133.1, 129.8, 128.9, 125.8,
124.5, 63.4, 23.8; IR (νmax, cmÀ 1): 2973 (b), 2923 (m), 1780 (s), 1722
(s), 1515 (s), 1416 (s), 1343 (s), 1200 (s), 847 (s), 764 (s), 695 (s);
HRMS (ESI) m/z: [M+H]+ calcd for C17H15N3O4 326.1136; found
326.1172.
°
°
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Larger Scale Synthesis Procedure
i) (S)-5-isopropyl-3-phenylimidazolidine-2,4-dione (3d)
5,5-dimethyl-3-(4-nitrophenyl)-1-(p–tolyl)hydantoin (5g) Synthe-
sized following general procedure B starting from 5,5-dimethyl-3-
(4-nitrophenyl)hydantoin (4e) (62 mg, 0.25 mmol) and bis(4-meth-
ylphenyl)iodonium triflate (2c) (138 mg, 0.30 mmol). The reaction
was stirred for 10 h. The reaction mixture was purified by column
chromatography (AcOEt/Hexane: 5/95 followed by 30/70) to afford
(S)-5-isopropylimidazolidine-2,4-dione (1e) (284 mg, 2 mmol) and
diphenyliodonium triflate (2a) (1.032 g, 2.4 mmol), CuI (38 mg,
0.2 mmol) and K3PO4 (424 mg, 2 mmol) were added under N2
atmosphere to a dried 50 mL round-flask. The flask was equipped
with a rubber septa, evacuated and backfilled with nitrogen three
times. The stirring was started and dry DCE (20 mL) was added. The
reaction mixture was stirred at room temperature for 12 h. The
reaction mixture was filtered through celite and concentrated in
vacuo. The mixture was purified by column chromatography
(AcOEt/Hexane: 5/95 followed by 40/60) to afford 3d (348 mg,
1.6 mmol, 80%) as white solid.
5g (71 mg, 0.21 mmol, 84%) as a white solid. Rf 0.5 (AcOEt /Hexane:
1
°
30/70). M.p. 186–188 C; H NMR (400 MHz, Chloroform-d): δ 8.32 (d,
J=8 Hz, 2H, ArH), 7.28 (d, J=8 Hz, 2H, ArH), 7.84 (d, J=8 Hz, 2H,
ArH), 7.17 (d, J=8 Hz, 2H, ArH), 2.42 (s, 3H, methyl), 1.58 (s, 6H,
methyl); 13C NMR (100 MHz, Chloroform-d): δ 174.6, 152.6, 145.8,
139.1, 137.7, 130.2, 128.9, 126.2, 124.1, 63.3, 23.6, 21.3; IR (νmax
,
cmÀ 1): 31125 (m), 2920 (b), 2923 (m), 1768 (s), 1723 (s), 1524 (s),
1411 (s), 1340 (s), 1203 (s), 849 (s), 762 (s); HRMS (ESI) m/z: [M+H]+
calcd for C18H17N3O4 340.1293; found 340.1306.
ii) 5,5-dimethyl-3-(4-nitrophenyl)-1-(p–tolyl)hydantoin (5g)
3-(4-fluorophenyl)-5,5-dimethyl-1-phenylhydantoin (5h) Synthe-
sized following general procedure B starting from 3-(4-fluorophen-
yl)-5,5-dimethylhydantoin (4p) (51 mg, 0.25 mmol) and diphenylio-
donium triflate (2a) (129 mg, 0.3 mmol). The reaction was stirred
for 12 h. The reaction mixture was purified by column chromatog-
raphy (AcOEt/Hexane: 5/95 followed by 30/70) to afford 5h (40 mg,
5,5-dimethyl-3-(4-nitrophenyl)hydantoin (4e) (498 mg, 2 mmol) and
bis(4-methylphenyl)iodonium triflate (2c) (1.099 g, 2.4 mmol), CuI
(38 mg, 0.2 mmol) and K3PO4 (424 mg, 2 mmol) were a“dded under
N2 atmosphere to a dried 50 mL round-flask. The flask was
equipped with a rubber septa, evacuated and backfilled with
nitrogen three times. The stirring was started and dry DCE (20 mL)
was added. The reaction mixture was stirred at room temperature
for 12 h. The reaction mixture was filtered through celite and
concentrated in vacuo. The mixture was purified by column
chromatography (AcOEt/Hexane: 5/95 followed by 20/80) to afford
5g (525 mg, 1.56 mmol, 78%) as white solid.
0.135 mmol, 54%) as a white solid. Rf 0.52 (AcOEt /Hexane: 30/70).
1
°
M.p. 158–160 C; H NMR (400 MHz, Chloroform-d): δ 7.51–7.43 (m,
5H, ArH), 7.33–7.31 (m, 2H, ArH), 7.19–7.14 (m, 2H, ArH), 1.55 (s, 6H,
methyl); 13C NMR (100 MHz, Chloroform-d): δ 175.3, 161.8 (d, JC-F
=
271 Hz), 153.6, 133.7, 129.6, 129.0, 128.8, 128.0, 127.7, 116.0 (d, JC-
F =7 Hz), 63.5, 24.0; 19F (376 MHz, Chloroform-d): δ À 112.16; IR (νmax
,
cmÀ 1): 3076 (m), 2987 (b), 1760 (s), 1710 (s), 1516 (s), 1417 (s), 1366
(s), 1204 (s), 1147 (s), 830 (s), 757 (s), 701 (s); HRMS (ESI) m/z: [M+
H]+ calcd for C17H15N2O2F 299.1191; found 299.1234.
Acknowledgements
4-(5,5-dimethyl-2,4-dioxo-3-phenylimidazolidin-1-yl)benzonitrile
(5i)[14] Synthesized following general procedure B starting from 3-
phenyl-5,5-dimethylhydantoin (4a) (51 mg, 0.25 mmol) and (4-
cyanophenyl)(mesityl)iodonium triflate (2m) (149 mg, 0.30 mmol).
The reaction was stirred for 12 h. The reaction mixture was purified
by column chromatography (AcOEt/Hexane: 5/95 followed by
This work was supported by the Research & Innovation Grant,
Tezpur University (TU/Fin/R/18-19/339) and by a Council of
Scientific and Industrial Research (CSIR), New Delhi fellowship to
R.A.S. We thank Dr. Sanjib Gogoi (CSIR-NEIST, Jorhat) for HRMS
experimental analyses.
30/70) to afford 5i (47 mg, 0.153 mmol, 62%) as a white solid. Rf
1
°
°
0.48 (AcOEt /Hexane: 30/70). M.p. 163–165 C (lit. 169 C); H NMR
(400 MHz, Chloroform-d): δ 7.77 (d, J=8 Hz, 2H, ArH), 7.55 (d, J=
8 Hz, 2H, ArH), 7.50–7.46 (m, 4H, ArH), 7.43–7.39 (m, 1H, ArH), 1.63
(s, 6H, methyl); 13C NMR (100 MHz, Chloroform-d): δ 174.4, 153.6,
138.9, 133.3, 131.2, 129.0, 127.8, 126.1, 118.0, 111.5, 63.8, 24.4; IR
(νmax, cmÀ 1): 2220 (s) 1777 (s), 1727 (s), 1497 (s), 1415 (s), 1345 (s),
1202 (s), 833 (s), 749 (s); HRMS (ESI) m/z: [M+H]+ calcd for
C18H15N3O2 306.1237; found 306.1276.
Conflict of Interest
The authors declare no conflict of interest.
Keywords: Copper
· Hypervalent iodine · Homogeneous
1-(4-fluorophenyl)-5,5-dimethyl-3-phenylhydantoin (5j) Synthesized
following general procedure B starting from 3-phenyl-5,5-dimeth-
ylhydantoin (4a) (51 mg, 0.25 mmol) and bis(4-fluorophenyl)iodo-
nium triflate (2f) (139 mg, 0.30 mmol). The reaction was stirred for
catalysis · N-arylation · Synthetic methods
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Manuscript received: October 9, 2020
Revised manuscript received: November 20, 2020
Accepted manuscript online: November 26, 2020
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R. Abha Saikia, D. Barman, A. Dutta,
Prof. A. Jyoti Thakur*
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1 – 12
N1- and N3-Arylations of Hydan-
toins Employing Diaryliodonium
Salts via Copper(I) Catalysis at
Room Temperature
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The N1- and N3-arylation of hydantoins
is reported employing diaryliodonium
triflates as aryl source using a copper
(I) catalyst. The developed protocol is
performable at room temperature and
easily scalable. The robustness is
confirmed with a wide range of
substrate studies of both hydantoins
and diaryliodonium salts. Sterically
complicated ortho-substituted diary-
liodonium salts are also compatible
with the reaction protocol.