Hetero Diels–Alder Reaction and Ene Reaction of Acylnitroso Species in situ Generated by Hypoiodite Catalysis

Article abstract of DOI:10.1002/ejoc.201801340

As a first non-metal-catalyzed oxidation for the in situ generation of acylnitroso species, we describe the hypoiodite catalysis using tetra-n-butylammonium iodide as precatalyst with tert-butyl hydroperoxide or hydrogen peroxide as a terminal oxidant. Th

Full text of DOI:10.1002/ejoc.201801340

DOI: 10.1002/ejoc.201801340
Communication
Hypoiodite Catalysis
Hetero Diels–Alder Reaction and Ene Reaction of Acylnitroso
Species in situ Generated by Hypoiodite Catalysis
[
a]
[a]
[a]
[b]
[c,d]
Saki Uraoka, Ikumi Shinohara, Hisato Shimizu, Keiichi Noguchi, Akira Yoshimura,
Viktor V. Zhdankin,[ and Akio Saito*
c,d]
[a]
Abstract: As a first non-metal-catalyzed oxidation for the in enes. Furthermore, the conversions of the representative HDA
situ generation of acylnitroso species, we describe the hypo- adduct to nitrone and 2-amino alcohols were demonstrated.
iodite catalysis using tetra-n-butylammonium iodide as precata- Compared with previous metal-catalyzed oxidation methods,
lyst with tert-butyl hydroperoxide or hydrogen peroxide as a this work provides a more efficient and environmentally friendly
terminal oxidant. This method can be applied to hetero Diels– procedure.
Alder (HDA) reactions with dienes and ene reactions with alk-
Introduction
N-Acylnitroso species are considered as extremely reactive and
useful intermediates in the hetero Diels–Alder (HDA) reactions
and ene reactions, which have been employed to synthesize a
[
1]
broad class of biologically active compounds. Commonly,
these unstable N-acylnitroso species are generated in situ from
hydroxamic acids and other precursors in these reactions. In the
HDA reactions, periodate salts have been traditionally and
widely used for the oxidation of hydroxamic acids (Scheme 1,
[
2]
[3a]
route a), although lead or silver oxide oxidation,
Swern–
and Dess–Martin oxidation are reported
as alternative methods. On the other hand, to the HDA reac-
[
3b]
[3c]
Moffat oxidation
Scheme 1. Generation and reactions of N-acylnitroso species.
[
4]
tions incompatible with these oxidation methods or to the
ene reactions, a two-step procedure based on the liberation
of acylnitroso species by thermolysis of anthracenyl cyclo-
adducts (route b) is frequently applied. Therefore, transition
metal-catalyzed oxidations of hydroxamic acids using tert-butyl
hydroperoxide (TBHP), hydrogen peroxide and dioxygen
[
5]
Normal-valent iodine[9] and hypervalent iodine[10] -catalyzed
oxidative transformations are of increasing importance owing
to their low toxicity, mild reactivity, easy handling and other
beneficial features. From this viewpoint, we have developed
metal-free synthesis of heterocycles based on iodine-cataly-
sis. As part of our studies, we very recently reported the HDA
reaction of acylnitroso species generated through the oxidation
[
6]
[
7]
[8]
have been developed as mild protocols covering relatively
broad scope in recent years. However, to the best of our knowl-
edge, non-metal-catalyzed oxidation is unknown for the in situ
generation of acylnitroso species.
[11]
of hydroxamic acids by (diacyloxyiodo)benzene, which is effec-
[12]
tive on cases of various dienes.
Furthermore, according to
Adam and Bottke's report, iodosylbenzene and (diacyloxy-
iodo)benzene are applicable to the ene reactions of acylnitroso
species. Therefore, considering the efficient utilization of iod-
ine reagents, the extension to the iodine-catalyzed generation
of acylnitroso species for HDA reaction and ene reaction was
attempted. Herein, we describe the HDA reaction and ene reac-
tion of acylnitroso species using catalytic tetra-n-butylammo-
nium iodide (TBAI) with TBHP or hydrogen peroxide.
[
a] Division of Applied Chemistry, Institute of Engineering, Tokyo University of
Agriculture and Technology,
[6a]
2
-24-16 Naka-cho, Koganei, Tokyo 184-8588, Japan
E-mail: akio-sai@cc.tuat.ac.jp
http://web.tuat.ac.jp/~akio-sai/index.html
[
[
[
b] Instrumentation Analysis Center, Tokyo University of Agriculture and
Technology
Tokyo, Japan
c] Department of Chemistry and Biochemistry, University of Minnesota
Duluth,
Duluth, MN 55812, USA
d] The Tomsk Polytechnic University,
Results and Discussion
6
34050 Tomsk, Russia
Initially, the screening of various iodine(I) precatalysts (5 mol-
%) and terminal oxidants (1.5 equiv.) was examined for the HDA
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.201801340.
Eur. J. Org. Chem. 0000, 0–0
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Communication
reaction of hydroxamic acid 1a and 1,3-cyclohexadiene (2a, 51–62 and 36–54 % yields, respectively (entries 11–22). Notably,
2
equiv.) in dichloromethane (DCM) at room temperature isoprene adducts 3ae–3ce were isolated as mixtures of regio-
(
Table 1, see Supporting information for evaluation of solvents). isomers (distal:proximal = 2:1 or 1:1, the ratios were determined
1
Regardless of the presence or absence of trifluoroacetic acid by H-NMR analysis). Unfortunately, in cases of sorbic acid as
(
3
TFA, 1.5 equiv.), λ -iodane catalysts generated from iodo- dienes, HDA reactions did not proceed.
benzene and m-chloroperbenzoic acid (mCPBA) afforded the
desired adducts 3aa in less than 10 % yields (entries 1 and 2).
On the other hand, a combination of iodide salts and TBHP led
to better results (entries 3–5). Particularly, by the use of TBAI as
a precatalyst, 3aa was obtained in 98 % yield (entry 5). Since
the yield of 3aa was reduced with a decrease in the catalytic
amount of TBAI (entry 7) and the HDA reaction did not proceed
in the absence of TBAI (entry 8), an active iodine species de-
rived from TBAI and TBHP would be involved in the present
reaction. The use of hydrogen peroxide instead of TBHP also
gave the good formation of 3aa (81 %, entry 10). It should be
mentioned that TBAI with TBHP or with hydrogen peroxide cat-
alytic system (entries 5 and 10) were more effective than TBA
periodate prepared in situ from TBABr and sodium periodate
Table 2. HDA reactions of hydroxamic acids 1 with dienes 2.
(
entries 12 and 13).
Table 1. Evaluation of precatalysts and terminal oxidants.
Entry
1
Precatalysts [mol-%]
Oxidants [equiv.]
3aa [%][a]
PhI (5)
PhI (5)
NaI (5)
mCPBA (1.5)
mCPBA (1.5)
TBHP (1.5)
TBHP (1.5)
TBHP (1.5)
TBHP (1.5)
TBHP (1.5)
TBHP (1.5)
9
0
[b]
2
3
4
5
6
7
8
9
1
1
1
1
38
74
98
60
64
0
4
Et NI (5)
TBAI (5)
TBAI (10)
TBAI (2)
–
–
30 % H
30 % H
2
O
O
2
(1.5)
(1.5)
0
0
1
2
3
TBAI (5)
TBAI (5)
TBABr (150)
TBABr (5)
2
2
81
43
21
70
2 3 2 2
Na CO ·H O (1.5)
NaIO
NaIO
4
(1.5)
(1.5)
4
[
3 2
a] Isolated yields. [b] Additive: CF CO H (1.5 equiv.).
Next, the HDA reactions of hydroxamic acids 1a–c with di-
enes 2a–e were investigated under the optimal conditions
Table 2). Similarly to the benzoyl derivative 1a (entry 1), the
(
carbamate analogues 1b (R = OBn) and 1c (R = OtBu) reacted
with 1,3-cyclohexadiene (2a, 2 equiv.) in the presence of TBAI
(
5 mol-%) and TBHP (1.5 equiv.) to give the corresponding HDA
adducts 3ba and 3ca in 92 and 91 % yields, respectively (entries
and 5). Also, the use of hydrogen peroxide as a terminal oxid-
3
ant afforded 3ba and 3ca in good yields (87 and 98 %, respec-
tively), although the increased amount of 2a (5 equiv.) was re-
quired (entries 4 and 6). In addition, in the reactions of 1a with
[
a] Isolated yields. [b] Distal:proximal = 2:1. [c] Distal:proximal = 1:1.
In most cases using 1a with 2d and 2e, we observed a by-
cyclopentadiene (2b) and 1b with 9,10-dimethylanthracene product such as benzoyl anhydride, which is known to be
2c), both conditions led to the good formation of 3ab and formed via the dimerization of benzoylnitroso compounds.[5b]
bc (74–94 %, entries 7–10). When 5 or 10 equivalents of 2,3- Therefore, these results suggest that acylnitroso species would
(
3
dimethyl-1,3-butadiene (2d) and isoprene (2e) were employed, be generated from 1a by the present catalytic system. Further-
these HDA adducts 3ad–3cd and 3ae–3ce were obtained in more, the regioselectivities of isoprene adducts 3ac–3cc are in
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Communication
[
7d,f,8d,f,12]
as well as the re- in ene reactions.[7c] Unfortunately, the ene reaction of hydrox-
consistency with experimental data
[
13]
sults of FMO and DFT calculations for HDA reactions of acyl- amic acids 1b and 1c with 1-octene did not proceed under the
nitroso species. The decline in regioselectivities of 3cc may be present conditions likely due to low reactivities of monosubsti-
[
6c,8a]
due to steric repulsion between a sterically hindered tert-butyl- tuted alkenes.
oxycarbonyl group of 1c with a 2-methyl substituent of iso-
prene.
The transformation of HDA adducts via the cleavage
[
14]
[15,16]
[17]
of N–O,
C–O
and C=C bonds
provides with various
molecular scaffolds and important frameworks. However, al-
though the C–O bond cleavage of bicyclic 1,2-oxazines (particu-
larly, bicyclo[2.2.1]oxazines) has been well studied by Miller's
[
15,16]
and other groups,
the selective and direct skeletal reorga-
nization of less strained bicyclo[2.2.2]oxazines such as 3aa to
nitrones including formation of 2-amino alcohols has been not
[
16d–16f]
achieved.
Therefore, on the basis of previous findings on
the formation of the cyclized intermediate 4 by through C–O
Scheme 3. Ene reactions of hydroxamic acids 1 with alkenes 4.
[
12]
bond cleavage of the cyclohexadiene adduct 3aa,
the con-
versions of 3aa to nitrone 5, 2-amino alcohols 6 and 7 were
performed (Scheme 2). Thus, after the treatment of 3aa with
trifluoromethanesulfonic acid (TfOH, 1.5 equiv.) in DCM at 40 °C
for 18 h, NaH (1.5 equiv.) was added to the reaction solution
affording nitrone 5 in 65 %. Notably, the use of saturated
To gain a better understanding of the active catalyst species
of the present catalytic oxidation of hydroxamic acid, we carried
out control experiments using the relevant iodine reagents in
the HDA reaction of 1a and 1,3-cyclohexadiene (2a, 2 equiv.) in
DCM (Table 3). Ishihara and co-workers disclosed that hypoio-
dite salt (unstable species) and triiodide salt are quickly gener-
ated from TBAI and TBHP according to Raman spectroscopic
NaHCO aqueous solution and Et N instead of NaH led to the
3
3
mixture of nitrone 5 and 2-amino alcohol 6. Furthermore, the
exposure of intermediate 4 to silica gel selectively gave the
ring-opening product 6 (CCDC-1863139 for 6-NAc,OAc),[18]
which was converted by zinc and HCl to 2-amino alcohols 7
[19]
analysis. Therefore, the triiodide salt derived from 1:1 mixture
of TBAI and molecular iodine was initially employed. However,
regardless of the addition of water, the HDA reaction did not
proceed along with the quantitative recovery of 1a (entries 1
and 2). On the other hand, the use of hypoiodite salt derived
from TBAOH (2 equiv., 10 % aqueous solution) and molecular
iodine (1 equiv.) afforded HDA adduct 3aa in 17 % yield after
[
18]
(CCDC-1863140)
via reduction of the hydroxyamino group
followed by O-to-N acyl migration.
3
h (entry 3), although the prolonged reaction times resulted
in a reduced yield of 3aa (entry 4). When the same amount
of water was added to TBAI-catalyzed reactions using TBHP or
hydrogen peroxide, the products 3aa were obtained in the sim-
ilar yields (entries 7 and 8). These results suggest that hypo-
iodite salt could be involved as the active catalyst. Although it
is known that triiodide salt is converted into iodate (but under
[
19]
basic conditions), the use of TBA iodate prepared in situ from
Scheme 2. Application of HDA adduct 3aa.
Table 3. Control experiments.
CCDC 1863139 (for 6-NAc,OAc),[18] which was converted by
zinc), and 1863140 (for 7) contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre.
To our delight, the present oxidation method could be ap-
plied to the ene reactions of hydroxamic acids 1b and 1c with
acyclic alkene 8a (10 equiv.) and cyclic alkene 8b (20 equiv.,
Scheme 3). Thus, by the use of TBAI (5 mol-%) in the presence
of TBHP (1.5 equiv.) in DCM, the corresponding N-allyl-hydrox-
amic acids 9ba, 9ca, 9bb and 9cb were obtained in 49–67 %
yields. On the other hand, the reactions of benzoyl derivative
Entry
1
Oxidants [equiv.]
TBAI (1), I (1)
Time [h]
3aa [%][a]
2
18
18
18
3
24
24
18
18
0
0
8
[b]
2
3
4
5
6
7
8
TBAI (1), I2 (1)
[
c]
TBAOH (2),
I
I
2
(1)
(1)
TBAOH (2),[
c]
17
13
2
TBABr (1), NaIO
TBABr (0.05), NaIO
TBAI (0.05), H (1.5)
TBAI (0.05), TBHP (1.5)
3
(1)
[d]
3
(1)
0
1
a with 8a brought about the desired product 9aa only in 22 %
[b]
b]
2
O
2
20
24
[
yield, which was determined by the conversion of O-acetyl de-
[
6a]
rivative 9aa-OAc. Under catalytic oxidation conditions, it was
reported that carbamate 1b showed the superior results to 1a
[
a] Isolated yields. [b] Additive: H
2
O (2.2 mL). [c] Additive: 10 % aq. solution.
[d] Considerable amount of 1a was recovered.
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Communication
3
583; c) N. E. Jenkins, R. W. Ware Jr., R. N. Atkinson, S. B. King, Synth.
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anhydrous conditions (entries 5 and 6).
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In conclusion, we have developed a catalytic and metal-free
generation of acylnitroso species from hydroxamic acids by the
hypoiodite catalysis using TBAI precatalyst with TBHP or
hydrogen peroxide. It was demonstrated that the present cata-
lytic system could be applied to HDA reactions with dienes and
ene reactions with alkenes. Furthermore, the conversions of bi-
cyclo[2.2.2]oxazine to nitrone and 2-amino alcohols can be per-
formed. Compared with previous metal-catalyzed oxidation
methods, this work provides a more efficient and environmen-
tally friendly procedure.
7
53.
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Experimental Section
Representative Procedure for the Preparation of 3: To a suspen-
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(
2
76.2 μL, 0.8 mmol) in DCM (2.0 mL) was added TBAI (7.4 mg,
0 μmol) and TBHP (109 μL, 0.6 mmol) at room temperature under
an argon atmosphere. After being stirred at room temperature for
8 h, the reaction mixture was quenched with sat. NaHCO and sat.
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1
3
Na S O , and then extracted with DCM. The organic layer was dried
with MgSO and concentrated in vacuo to dryness. The residue was
purified by preparative thin layer chromatography (R = 0.17, hex-
ane/EtOAc = 3:1) to give 3aa (84.3 mg, 98 %) as a white solid.
2
2 3
4
f
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1
13
H and C NMR spectra of all products.
Acknowledgments
This work was partially supported by JSPS Grants-in-Aid for Sci-
entific Research (C) (Grant No 15K07852) and by JSPS Fund for
the Promotion of Joint International Research (Grant No
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1
6KK0199). A. Y. and V. V. Z. are thankful to Tomsk Polytechnic
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018) and to Russian Science Foundation (RSF-16-13-10081).
3
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Keywords: Acylnitroso · Catalysis · Cycloaddition · Ene
reaction · Iodine
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[
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[18] The structure of product 6 was determined by single-crystal X-ray analy-
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firmed by its own X-ray structure. See Supporting information for further
details.
1
[
[
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Received: September 1, 2018
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Communication
Hypoiodite Catalysis
S. Uraoka, I. Shinohara, H. Shimizu,
K. Noguchi, A. Yoshimura,
V. V. Zhdankin, A. Saito* .................. 1–6
Hetero Diels–Alder Reaction and
Ene Reaction of Acylnitroso Species
in situ Generated by Hypoiodite Ca-
talysis
First example of hypoiodite-catalyzed in hetero Diels–Alder reactions with di-
oxidation for the in situ generation of enes and in ene reactions with alk-
acylnitroso species, which can be used enes.
DOI: 10.1002/ejoc.201801340
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