Saccharin-based μ-oxo imidoiodane: A readily available and highly reactive reagent for electrophilic amination

Article abstract of DOI:10.1002/chem.201500335

Three new saccharin-based hypervalent iodine compounds were prepared by the reaction of saccharine with (diacetoxyiodo)arenes or acetoxybenziodoxole. Structures of these new imidoiodanes were established by X-ray crystallography. The saccharin-based μ-oxo-bridged imidoiodane readily reacts with silyl enol ethers under mild conditions to give the corresponding α-aminated carbonyl compounds in moderate yields. Sweet saccharin: Three new saccharin-derived hypervalent iodine compounds were prepared by the reaction of saccharine with (diacetoxyiodo)arenes or acetoxybenziodoxole. The saccharin-based μ-oxo-bridged imidoiodane readily reacts with silyl enol ethers to give the corresponding α-aminated carbonyl compounds in moderate yields.

Full text of DOI:10.1002/chem.201500335

DOI: 10.1002/chem.201500335
Communication
&
Organic Synthesis
Saccharin-Based m-Oxo Imidoiodane: A Readily Available and
Highly Reactive Reagent for Electrophilic Amination
Akira Yoshimura,*[a] Steven R. Koski,[a] Jonathan M. Fuchs,[a] Akio Saito,[b] Victor N. Nemykin,[a]
and Viktor V. Zhdankin*[a]
strated that these new imidoiodanes are useful nitrogen trans-
Abstract: Three new saccharin-based hypervalent iodine
compounds were prepared by the reaction of saccharine
fer reagents in reactions with alkenes, alkynes, and allenes.[4]
Togo and co-workers have reported the nitrogen-containing
with (diacetoxyiodo)arenes or acetoxybenziodoxole. Struc-
hypervalent iodine(III) compound, bis(phthalimido)iodoben-
tures of these new imidoiodanes were established by X-
zene, as an active intermediate species in the Hofmann rear-
rangement reaction.[5] Minakata and co-workers have also de-
ray crystallography. The saccharin-based m-oxo-bridged
imidoiodane readily reacts with silyl enol ethers under
scribed the oxidative decarboxylative nitrogenation reaction of
mild conditions to give the corresponding a-aminated car-
b,g-unsaturated carboxylic acids by using bis(ditosylimido)-
bonyl compounds in moderate yields.
iodobenzene or bis(phthalimido)iodobenzene as the nitrogen
source.[6]
In a search for readily available electrophilic aminating re-
In recent years, hypervalent iodine reagents have emerged as
environmentally friendly and efficient oxidizing reagents for
various synthetically useful oxidative transformations.[1] Particu-
larly important are hypervalent iodine(III) compounds with
iodineÀnitrogen bonds,[2] such as azidoiodanes,[2a–e] benziod-
azoles,[2f,g] amidobenziodoxoles,[2j] and iminoiodanes,[2j–o] all of
which are efficient reagents for CÀN bond forming reactions.
Representative recent examples of synthetic applications of
these reagents include direct azidation, amination, imidation,
aziridination, metal-catalyzed imidation, and CÀH insertion re-
actions.[2] Most of these studies[2] were performed by using
cyclic or pseudocyclic hypervalent iodine reagents; in contrast,
non-cyclic imidoiodanes of the types ArI(NR2)2 or ArI(NR2)OR
are uncommon compounds and, with a few exceptions, their
reactivity has not been investigated. In particular, Varvoglis and
co-workers first reported the synthesis and reactions with ke-
tones of several hypervalent iodine(III) bisimidiates, such as
bis(saccharin)iodobenzene, bis(succinimide)iodobenzene, and
bis(phthalimido)iodobenzene.[3] More recently, Muniz and co-
workers have reported the preparation of new bis(imido)iodo-
benzenes, acetoxy(imido)iodobenzenes, and m-oxo-bridged bi-
s(imido)iodobenzenes, and these compounds were character-
ized by X-ray crystallography. The same group has also demon-
agents with enhanced reactivity, we decided to investigate sac-
charin-based m-oxo-bridged imidoiodanes. The m-oxo-bridged
hypervalent iodine derivatives are known compounds and sev-
eral examples of their crystal structures have been previously
reported.[7] Enhanced reactivity of m-oxo-bridged hypervalent
iodine(III) compounds has been reported by Kita[8a–g] and other
groups.[8h,i] However, to the best of our knowledge, m-oxo-
bridged imidoiodanes derived from cyclic imides have not
been previously reported.
Herein, we report the design, preparation, structural investi-
gation, and reactivity of new m-oxo-bridged bis(saccharin)iodo-
benzene and several other saccharin-based hypervalent iodine
compounds.
The m-oxo-bridged bis(saccharin)iodobenzene 1a was syn-
thesized in moderate yield by a one-pot procedure from (di-
acetoxyiodo)benzene (1.0 equiv) and saccharin (1.1 equiv) in
methylene chloride in the presence of water by stirring for
24 h at room temperature (Scheme 1). For comparison, two ad-
ditional saccharin derivatives, bis(saccharinyl)iodobenzene 1b
and saccharinylbenziodoxole 1c, were also prepared from sac-
charin and the corresponding iodine(III) acetates (Scheme 1).
Two of these saccharin derivatives, 1a and 1c, were character-
ized by single-crystal X-ray crystallography.
X-ray crystal data for products 1a and 1c demonstrate the
presence of both iodineÀnitrogen and iodineÀoxygen bonds
in the molecule (Figure 1). The lengths of these bonds are simi-
lar to the previously reported structures of imidoiodanes and
m-oxo-bridged iodine(III) compounds.[2b,4f,g,7]
[a] Dr. A. Yoshimura, S. R. Koski, J. M. Fuchs, Prof. Dr. V. N. Nemykin,
Prof. Dr. V. V. Zhdankin
Department of Chemistry and Biochemistry
University of Minnesota Duluth, Duluth, MN 55812 (USA)
E-mail: ayoshimu@d.umn.edu
In the initial reactivity study of compounds 1, we investigat-
ed the a-saccharinization reaction by using the silyl enol ether
of acetophenone 2a (1 equiv) with m-oxo-bridged bis(sacchari-
nyl)iodobenzene 1a as the nitrogen source (0–2 equiv) under
various reaction conditions in the presence of trifluorometh-
anesulfonic acid as additive (1 equiv). In the absence of io-
dine(III) reagent 1a, the reaction of silyl enol ether 2a and sac-
vzhdanki@d.umn.edu
Homepage: http://www.d.umn.edu/~vzhdanki/
[b] Prof. Dr. A. Saito
Division of Applied Chemistry, Institute of Engineering
Tokyo University of Agriculture and Technology
2-24-16 Naka-cho, Koganei, Tokyo 184-8588 (Japan)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201500335.
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Table 1. Optimization of a- saccharinization of silyl enol ether 2a.[a]
Entry
1a [equiv]
Solvent
t [h]
3a [%][b]
1[c]
2[c]
3[c]
4[c]
5[c]
6[c]
7[c]
8
0
1
1
1
1
1
1
1
0.6
0.6
1.2
0.6
MeCN
MeCN
Et2O
24
24
24
24
24
24
24
12
2
0
56
<1
<1
23
17
0
69
70 (68)[d]
37 (33)
35 (32)
1
CHCl3
acetone
MeOH
EtOAc
MeCN
MeCN
MeCN
MeCN
MeCN
9
Scheme 1. Preparation of saccharin-based hypervalent iodine(III) compounds
1a–1c.
10[e]
11[f]
12[g]
2
2
24
[a] Reactions were performed in the specified solvent at room tempera-
ture for several hours using iodine(III) reagent 1a (0–1 equiv), and siyl
enol ether 2a (1 equiv). [b] Yields of product 3a were determined from
1H NMR spectra of reaction mixtures (numbers in parentheses show
yields of isolated product 3a). [c] Trifluoromethanesulfonic acid (1 equiv)
was used as additive in this reaction. [d] Isomeric byproduct 4a was iso-
lated in 29%. [e] Iodine(III) reagent 1b was used instead of 1a. [f] Io-
dine(III) reagent 1c was used instead of 1a. [g] Acetophenone was used
instead of 2a.
matic (2-furanyl and 3-pyridine) silyl enol ethers, both isomeric
products 3 and 4 were obtained in comparable yields (en-
tries 10 and 11 and the Supporting Information). It is notewor-
thy that the reactions of silyl enol ethers of secondary ketones
under optimized conditions gave the CÀN bonded products 3
in lower yields (entries 12–15), whereas the CÀO bonded struc-
tural isomers 4 were the major products isolated in 52–74%
yield (see the Supporting Information). Similar selectivity
trends in the oxidative imidation reactions of ketones were
previously reported by other groups, and our results are in
agreement with these reports.[9] The structures of 3j and 4l
were established by single-crystal X-ray analysis (see the Sup-
porting Information for details).
Figure 1. X-ray crystal structures of compounds 1a and 1c.
charine failed to produce the desired product 3a (Table 1,
entry 1), whereas in the presence of reagent 1a the reaction
resulted in the formation of product 3a (entry 2). Comparison
of different solvents demonstrated that acetonitrile is most
suited for this reaction (Table 1, entries 2–7). Further studies re-
vealed that reactions in acetonitrile in the absence of trifluoro-
methanesulfonic acid afforded product 3a in improved yield
(69% yield, entry 8), and decreasing the amount of iodine(III)
reagent 1a from 1 to 0.6 equivalents did not reduce the yield
of product 3a (entry 9). An isomeric product of O-alkylation,
compound 4a, was also isolated in this reaction as a minor
product (29% yield, entry 9). Structures of isomeric products
3a and 4a were established by single-crystal X-ray analysis
(see the Supporting Information for details). The similar reac-
tions of silyl enol ether 2a with reagents 1b and 1c afforded
products 3a and 4a in lower yields, which demonstrates that
m-oxo-bridged reagent 1a has higher reactivity compared with
1b and 1c.
Using the optimized reaction conditions, we investigated
the conversion of various substituted silyl enol ethers, 2, to the
respective a-saccharinated derivatives, 3, and isomeric byprod-
ucts, 4 (see the Supporting Information). In general, all aryl-
substituted silyl enol ethers with electron-donating or elec-
tron-withdrawing substituents in the aromatic ring afforded
the corresponding a-saccharinated products 3 in moderate to
good yields (Table 2, entries 1–9). In the reactions of heteroaro-
Recently, Kita and co-workers have reported that heterocy-
clic dinuclear hypervalent iodine(III) reagents (e.g., compound
5 in Scheme 2) demonstrate especially high reactivity in oxida-
tive spirolactamization reactions.[8a–g] Thus, we have prepared
the similar dinuclear heterocyclic disaccharin derivative 6
(Scheme 2). The structure of product 6 was established by
single-crystal X-ray analysis (Scheme 2, see the Supporting In-
formation for details). We tested compound 6 in the a-saccha-
rinization reaction with 2a under our optimized conditions. No
products 3a and 4a were formed in these reactions, which
may be explained by the steric bulkiness and rigidity of the
structure of compound 6.[8a]
In conclusion, we have reported the preparation, X-ray struc-
ture, and reactivity of new m-oxo-bridged saccharin-derived hy-
pervalent iodine(III) reagent 1a. This new reagent reacts with
silyl enol ethers under mild conditions, affording products of
a-saccharinization in moderate yields.
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Table 2. Reactions of silyl enol ether 2 with m-oxo reagent 1a under opti-
mized conditions.[a]
Table 2. (Continued)
Entry
14
2
Product 3 [yield][b,c]
Entry
1
2
Product 3 [yield][b,c]
2n
2o
3n (40%)
3o (23%)
2a
2b
2c
2d
2e
2 f
3a (68%)
15
2
3
4
5
6
3b (60%)
[a] All reactions of 1a (0.6 equiv) with silyl enol ethers 2 were performed
in MeCN at room temperature for 2 h. [b] Yields of isolated products.
[c] Isomeric products 4 were also isolated from the reaction mixture (see
the Supporting Information).
3c (62%)
3d (62%)
3e (63%)
3 f (61%)
7
8
9
2g
2h
2i
3g (47%)
3h (54%)
3i (46%)
Scheme 2. Preparation and X-ray crystal structure of heterocyclic dinuclear
hypervalent iodine reagent 6.
Experimental Section
Synthesis of 1a
Water (2 mL) was added to a stirring mixture of (diacetoxyiodo)-
benzene (322 mg, 1.0 mmol) and saccharin (202 mg, 1.1 mmol) in
CH2Cl2 (2 mL). The reaction was stirred at 25oC for 24 h. After com-
pletion of the reaction, the precipitate was filtered and washed
with dichloromethane, then washed several times with diethyl
ether and dried in vacuum to give compound 1a (481 mg, 61%)
as a white solid.
10
11
12
2j
3j (33%)
3k (43%)
2k
Typical reaction of 1a with 2
Freshly prepared silyl enol ether 2 (0.25 mmol) was added to a solu-
tion of m-oxo imidoiodane 1a (118 mg, 0.15 mmol) in acetonitrile
(1.5 mL). The reaction mixture was stirred at room temperature for
2 h (monitored by TLC for full conversion of silyl enol ether 2). The
resulting solution was concentrated under reduced pressure. Purifi-
cation by column chromatography on silica gel (hexane/ethyl ace-
2l
3l (24%)
13
2m
3m (22%)
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This work was supported by a research grant from the National
Science Foundation (CHE-1262479). We are grateful to Rigaku
Co., Ltd. for computational support for the X-ray structural
analysis.
Keywords: amination · hypervalent · iodine · oxidation ·
saccharin
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Received: January 26, 2015
Published online on February 18, 2015
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