Aniline-Type Hypervalent Iodine(III) for Intramolecular Cyclization via C?H Bond Abstraction of Hydrocarbons Containing N- and O-Nucleophiles

Article abstract of DOI:10.1002/adsc.202100316

We developed a method for the preparation of (diacetoxyiodo)-2-(N-alkylamido)benzene as an aniline-type hypervalent iodine(III). We also achieved direct cyclizations via C?H bond abstraction, such as the Hofmann-L?ffler-Freytag reaction, a direct amination, and a direct lactonization, using the aniline-type hypervalent iodine(III) to obtain corresponding products in high yields. (Figure presented.).

Full text of DOI:10.1002/adsc.202100316

UPDATES
DOI: 10.1002/adsc.202100316
Aniline-Type Hypervalent Iodine(III) for Intramolecular
Cyclization via CÀ H Bond Abstraction of Hydrocarbons
Containing N- and O-Nucleophiles
Yuna Nishiguchia and Katsuhiko Moriyamaa,*
a
Department of Chemistry, Graduate School of Science and Soft Molecular Activation Research Center, Chiba University, 1-33
Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Phone: (+81)-43-290-3693
Fax: (+81)-43-290-3693
E-mail: moriyama@faculty.chiba-u.jp
Manuscript received: March 12, 2021; Revised manuscript received: April 23, 2021;
Version of record online: ■■■, ■■■■
Supporting information for this article is available on the WWW under https://doi.org/10.1002/adsc.202100316
benziodoxazoles[8] as aniline-type hypervalent iodines
(V) by Zhdankin and co-workers (Figure 1B), no
aniline-type hypervalent iodine(III) has been synthe-
sized. On the other hand, the direct intramolecular
Abstract: We developed a method for the prepara-
tion of (diacetoxyiodo)-2-(N-alkylamido)benzene as
an aniline-type hypervalent iodine(III). We also
achieved direct cyclizations via CÀ H bond abstrac-
cyclization via CÀ H bond abstraction of hydrocarbons
tion, such as the Hofmann-Löffler-Freytag reaction,
containing nucleophiles has attracted considerable
a direct amination, and a direct lactonization, using
attention recently as an elegant and atom-economical
the aniline-type hypervalent iodine(III) to obtain
approach.[9] As an example of a transition metal-free
corresponding products in high yields.
direct intramolecular cyclization, we cite the work of
Muñiz and co-worker, who developed an iodine-
catalyzed Hofmann-Löffler-Freytag reaction of N-alkyl
Keywords: Aniline; CÀ H bond activation; Hetero-
sulfonamides via the effect of ligand (m-ClÀ C6H4CO2)
cycles; Hypervalent iodine; Intramolecular cycliza-
on λ3-iodane (PhI(m-ClÀ C6H4CO2)2).[10] Kita and co-
tion
workers succeeded in a direct lactonization of carbox-
ylic acids using p-anisiodine(III) diacetate in the
presence of a stoichiometric amount of KBr.[11] In
Hypervalent iodine compounds have been utilized 2019, Nagib and co-workers developed an I2-catalyzed
extensively in lieu of transition metals as environ- direct intramolecular amination of imidates with PhI
mentally friendly reagents for unique transformations (OAc)2 in polar solvent under thermal conditions, in
in organic synthesis.[1] The design of hypervalent which subsequent hydrolysis of resulting oxazolines
iodine compounds has been actively pursued to resolve with aq. HCl furnished the corresponding β-amino
such issues as chemoselectivity of oxidation and alcohols.[12]
stability and solubility in organic solvent. Various
We report herein a preparation of (diacetoxyiodo)-
alkyl- and alkoxy-substituted hypervalent iodine(III) 2-(N-alkylamido)benzene as a novel aniline-type hy-
compounds were developed for catalytic reactions, pervalent iodine(III) and a direct intramolecular cycli-
enantioselective reactions, reactions with recyclable zation with the compound.
iodoarene, and so forth.[2] Tether hypervalent iodines
(Diacetoxyiodo)-2-(N-alkylamido)benzenes
(1)
(III) bearing sulfonyl,[3] phosphinate,[4] boronate,[5] and were prepared in three steps from commercially
nitro[6] groups were developed by Protasiewicz, Balth- available 2-iodoaniline (Scheme 1). A precursor of
azor, Zhdankin, and Nikiforov groups, respectively hypervalent iodine(III) (B) was synthesized by acyla-
(Figure 1A). A strategic motif that utilizes an aniline tion or sulfonylation of 2-iodoaniline and subsequent
skeleton for the design of hypervalent iodine has alkylation of amide (A). Oxidation of B with
allowed the installation of two different functional NaBO3 ·4H2O in AcOH provided desired (diacetoxyio-
groups on the nitrogen center to construct a suitable do)arenes (1).
reactive site. However, despite the successful synthesis
of and methylbenzamido)benzene (1h) was obtained by sin-
The solid-state structure of (diacetoxyiodo)-2-(N-
N-(2-iodylphenyl)acylamides[7]
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Figure 2. X-ray structures of 1h; ellipsoids at 50% probability.
°
°
Selected lengths (Å), angles ( ), and torsions ( ).; I1-O2
°
°
2.140 Å, I1-O4 2.155 Å, C1-I1-O2 82.83 , C1-I1-O4 81.58 ,
°
°
°
C2-N1-C7 126.19 , C2-N1-C14 115.38 , O2-I1-C1-C2 111.20 ,
°
°
O4-I1-C1-C2 67.78 , C7-N1-C2-C1 65.43 , C14-N1-C2-C1
°
109.71 .
Table 1. Screening for optimum conditions for the Hofmann-
Löffler-Freytag reaction of 2a.
Figure 1. Designed hypervalent iodines and intramolecular
cyclization with ArI(OR)2.
Entry
ArI(OAc)2
(x equiv.)
y
Time
(h)
Yield
(%)[a]
1
2
3
4
5
6
7
8
1a (1.0)
1b (1.0)
1c (1.0)
1d (1.0)
1e (1.0)
1f (1.0)
1g (1.0)
1h (1.0)
1i (1.0)
1j (1.0)
1k (1.0)
1h (1.2)
1i (1.2)
1h (1.2)
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
5.0
5.0
5.0
15
15
15
15
15
15
15
15
15
15
15
15
15
8
31 [59]
63 [26]
63 [23]
69 [9]
59 [32]
70 [13]
59 [18]
78 [16]
81 [10]
69 [9]
69 [10]
97
Scheme 1. Preparation of (diacetoxyiodo)-2-(N-alkylamido)
benzene (1).
9
gle-crystal X-ray crystallography.[13] Interestingly, the
structure indicated that the diacetoxyiodanyl group and
the amide group on 1h are perpendicular to the
benzene ring on the iodoaniline skeleton (O2-I1-C1-
10
11
12
13
14
89 [8]
96
°
°
C2=111.20 , C7-N1-C2-C1=65.43 , O4-I1-C1-C2=
°
°
67.78 , C14-N1-C2-C1=109.71 ) and parallel to each
[a] Numbers in brackets indicate recovery of 2a.
°
°
other (O2-I1-N1=101.76 , I1-N1-C8=73.48 , O4-I1-
°
N1=66.64 , I1-N1-C14=118.62)(Figure 2).
To accomplish the I2-catalyzed Hofmann-Löffler-
Freytag reaction of N-alkyl sulfonamides (2), first, we was used in the presence of catalytic I2 (2.5 mol%) in
screened for the optimum aniline-type (diacetoxyiodo) CH2Cl2, 2-phenyl-pyrrolidine derivative (3a) was
arenes(III) (1) in the reaction with 2a (Table 1). When obtained in 31% yield (Entry 1). Switching the alkyl
(diacetoxyiodo)-2-(N-n-butyl-tosylamido)benzene (1a) group to a Me group instead of a n-Bu group of ArI
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(OAc)2 (1b–1g) improved the yield of 3a to 59–70% alkyl-substituted (2q and 2r) and aliphatic (2s)
(Entries 2–7). The use of (diacetoxyiodo)-2-(N-meth- benzene sulfonamides, as well as other sulfonyl
ylarylamido)benzenes 1h and 1i further increased the groups, such as Ts (2t), Ms (2u), 4-meth-
yield of 3a to 78% and 81%, respectively (Entries 8 oxybenzenesulfonyl (Mbs) (2v), and Ns (2w) groups,
and 9), whereas the use of 1j and 1k did not improve also provided desired products (3q–3w) in high yields
the yield of 3a (Entries 10 and 11). In the case of (68–93%). When inner sulfonamide (2x) and O-benzyl
increased amounts of ArI(OAc)2 (1.2 equiv.) and I2 sulfonamide (2y) as variant sulfonamides were em-
(5 mol%) in the reaction, the use of 1h rather than 1i ployed in the reaction, 3-substituted γ-sultam (3x) and
generated 3a in a higher yield (Entries 12 and 13). 2-substituted oxazoline (3y) were obtained in 64% and
Shortening the reaction time to 8 h in the reaction 89% yields, respectively. It is noteworthy that the use
using 1h (1.2 equiv.) and I2 (5 mol%) provided 3a in of 1h is extremely effective for the reaction of
96% yield (Entry 14).
To explore the substrate scope of the Hofmann- 2g, 2i, and 2o).
Löffler-Freytag reaction, N-alkyl sulfonamides (2) We investigated
substrates bearing electron-withdrawing arenes (i.e.,
a
direct amination of
were examined under the optimum reaction conditions trichloromethyl acetimidates (4) and a direct lactoniza-
(Table 1, Entry 14) (Scheme 2). Treatment of benzene tion of carboxylic acids (6) to clarify the versatility of
sulfonamides bearing p-electron-donating group and p- the direct intramolecular cyclization with aniline-type
electron-withdrawing group substituted arenes (2b– hypervalent iodine(III) (1). With regard to the direct
2i), m-substituted (2j) and o-substituted arenes (2k amination of trichloromethyl acetimidates (4), the
and 2l), 2-naphthyl (2m), and disubstituted arenes optimum reaction conditions were 4a, ArI(OAc)2 (1h)
(2n–2p) furnished corresponding products (3b–3p) in (1.2 equiv.), I2 (1.0 equiv.), and K2CO3 (1.0 equiv.) in
high yields (72–98%), respectively. The reaction of CH2Cl2 at room temperature (Method A), which gave
4,5-dihydro-4-phenyl-2-trichloromethyl oxazole (5a)
in quantitative yield (Scheme 3). Various trichloroace-
timidates bearing electron-donating group and elec-
tron-withdrawing group substituted arenes (4b–4g)
also furnished corresponding products (5b–5g) in high
yields (86–>99%). Additionally, we achieved an I2-
catalyzed direct amination of trichloroacetimidates (4)
to obtain desired products (5b–5g) in 52–96% yields
(Method B).
Furthermore, we developed a direct lactonization of
carboxylic acid (6), which involves an intramolecular
cyclization of an oxygen nucleophile with 1h
(Scheme 4). The optimum reaction conditions were
6a, 1h (1.5 equiv.), and HBr (in AcOH, 1.2 equiv.) in
CH2Cl2 at room temperature, which afforded lactone
Scheme 2. Hofmann-Löffler-Freytag reaction of sulfonamides
(2). a) I2 (1.0 equiv.), b) I2 (50 mol%), c) I2 (20 mol%), and d)
K2CO3 (1.2 equiv.).
Scheme 3. Direct amination of trichloromethyl acetimidates (4).
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products in high yields. Aniline-type hypervalent
iodine(III) can be utilized in various transformations
including iodoarene-catalyzed reactions. The develop-
ment of novel aniline-type hypervalent iodine(III)
chemistry is underway in our laboratory.
Experimental Section
Procedure for Hofmann-Löffler-Freytag Reaction
of Sulfonamides (2)
To a solution of 2a (57.9 mg, 0.20 mmol) in CH2Cl2 (1.0 mL)
was added 1h (109.3 mg, 0.24 mmol) and iodine (2.5 mg,
°
0.01 mmol) at 0 C, and the reaction mixture was stirred at
room temperature for 8 h under fluorescent light (60 W
fluorescent lamp; the distance between the fluorescent lamp and
the reaction tube was 10 cm). Saturated Na2SO3 aqueous
solution (5.0 mL) was added to the mixture, and the product
was extracted with CHCl3 (10 mL×3). The organic phase was
washed with Saturated NaHCO3 aqueous solution (20 mL) and
dried over Na2SO4. The organic phase concentrated under
reduced pressure, and the crude products was purified by
column chromatography (eluent: hexane/AcOEt=4:1) to give
the desired product 3a (55.2 mg, 96% yield).
Scheme 4. Direct lactonization of carboxylic acids (6). a) 1h
(1.2 equiv.) and HBr in AcOH (1.0 equiv.).
(7a) in 89% yield. Use of carboxylic acids containing
various substituted arenes (6b–6e) and o-alkyl benzoic
acid (6f) in the reaction also furnished corresponding
lactams (7b–7f) in 58–85% yields.
A comparative experiment between 1h and PhI
(OAc)2 in these direct cyclization reactions indicated
that the reactivity of 1h is superior to that of PhI
(OAc)2 in terms of delivering high product yields
(Scheme 5). In this regard, the reaction of 2h, 2q, 2s,
and 6c with PhI(OAc)2 under the same conditions as
those with 1h gave corresponding products 3h, 3q,
3s, and 7c in 78%, 64%, 55%, and 56% yields,
respectively.
Procedure for Direct Amination of Trichloromethyl
Acetimidates (4)
To a solution of 4a (53.3 mg, 0.20 mmol) in CH2Cl2 (1.0 mL)
was added K2CO3 (27.6 mg, 0.20 mmol), 1h (109.3 mg,
°
0.24 mmol) and iodine (50.8 mg, 0.20 mmol) at 0 C, and the
reaction mixture was stirred at room temperature for 3 h under
fluorescent light (60 W fluorescent lamp; the distance between
the fluorescent lamp and the reaction tube was 10 cm).
Saturated Na2S2O3 aqueous solution (5.0 mL) was added to the
In conclusion, we developed a method for the mixture, and the product was extracted with CHCl3 (10 mL×3).
The organic phase was dried over Na2SO4. The organic phase
concentrated under reduced pressure, and the crude products
was purified by column chromatography (eluent: hexane/AcOEt
=20:1) to give the desired product 5a (52.6 mg, >99% yield).
preparation
of
(diacetoxyiodo)-2-(N-alkylamido)
benzene (1) as a novel aniline-type hypervalent iodine
(III) and identified the structure of 1h, which is
characterized by a parallel configuration between the
diacetoxyiodanyl group and the amide group on 1h. In
addition, direct cyclization reactions via CÀ H bond
abstraction, such as the Hofmann-Löffler-Freytag
reaction, direct amination, and direct lactonization,
using 1h were achieved to obtain corresponding
Procedure for Direct Lactonization of Carboxylic
Acids (6)
To a solution of 6a (32.8 mg, 0.20 mmol) in CH2Cl2 (2.0 mL)
was added 1h (136.6 mg, 0.30 mmol) and 25% HBr in AcOH
°
solution (59.7 μl, 0.24 mmol) at 0 C, and the reaction mixture
was stirred at room temperature for 22 h under fluorescent light
(60 W fluorescent lamp; the distance between the fluorescent
lamp and the reaction tube was 10 cm). Saturated NaHCO3
°
aqueous solution (5.0 mL) was added to the mixture at 0 C, and
°
the mixture was stirred at 0 C for 5 min. The product was
extracted with CHCl3 (10 mL×3). The organic phase was
washed with saturated NaHCO3 aqueous solution (10 mL) and
dried over Na2SO4. The organic phase concentrated under
reduced pressure, and the crude products was purified by
column chromatography (eluent: hexane/AcOEt=4:1) to give
the desired product 7a (28.8 mg, 89% yield).
Scheme 5. Comparison between 1h and PhI(OAc)2 in these
direct cyclizations.
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Acknowledgements
This work was supported by a Grant-in-Aid for Scientific
Research (No. G19K05469) from the Ministry of Education,
Culture, Sports, Science and Technology of Japan (K.M.).
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Adv. Synth. Catal. 2021, 363, 1–6
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Aniline-Type Hypervalent Iodine(III) for Intramolecular Cyc-
lization via CÀ H Bond Abstraction of Hydrocarbons Contain-
ing N- and O-Nucleophiles
Adv. Synth. Catal. 2021, 363, 1–6
Y. Nishiguchi, K. Moriyama*