Room temperature iron(ii)-catalyzed radical cyclization of unsaturated oximes with hypervalent iodine reagents

Article abstract of DOI:10.1039/c9ob02424g

Here, we disclose an iron(ii)-catalyzed I-O bond cleavage of Koser's hypervalent iodine reagents (HIRs) that initiated the radical cyclization of unsaturated oximes at room temperature. This strategy is successfully applied for the construction of the isoxazoline backbone in an efficient manner. In particular, the direct introduction of a TsO group into products facilitates their late-stage transformations in organic synthesis.

Full text of DOI:10.1039/c9ob02424g

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DOI: 10.1039/C9OB02424G
Organic & Biomolecular Chemistry
ARTICLE
Room temperature iron(II)-catalyzed radical cyclization of
unsaturated oximes with hypervalent iodine reagents
Shichao Yang,a Hongji Li,*a Pinhua Li,a Jingya Yang,a and Lei Wang *a,b
Received 00th January 2019,
Accepted 00th January 2019
DOI: 10.1039/x0xx00000x
Here, we disclose an iron (II)-catalyzed IO bond cleavage of Koser’s hypervalent iodine reagents (HIRs) that initiated the
radical cyclization of unsaturated oximes at room temperature. This strategy is successfully applied for the construction of
isoxazoline backbone in an efficient way. In particular, the direct introduction of TsO group into products facilitates their
late-stage transformations in organic synthesis.
www.rsc.org/
Previous work: Cleavge of I-O bond using Fe catalysis and PIDA
Introduction
OR
Fe(CO)3 (10 mol %)
R
PhI(OR)2
PhI(OR)2
(a)
(b)
Ar
Ar
CH3CN, 70 oC, 12 h
Over the past decades, hypervalent iodine reagents (HIRs)
have been widely employed for the synthesis of complex
organic molecules due to their easy preparation, ubiquitous
property and synthetic versatility.1 Classically, HIRs in reported
works can function as reactive substrate, oxidant and both of
them, as well as acting as a promoter in some reaction
systems.1-3 Among them, a number of the elegant reactions
mainly depended on the combination of HIRs and transition
metal catalysts. These metal catalysts include Pd,3a,b Cu,3c Fe,3e-
N
N
Fe(acac)2 (5 mol %)
PhMe, N2, 70 oC, 8 h
Ar
Ar
OR
This work: Fe(II)-catalyzed radical cyclization of oximes with HIRs
O
OH
N
S
R1
O
O
N
OH
I
O
O
O
Fe(acac)2 (5 mol %)
DCM, air, rt
S
R1
(c)
R
R
Ph
O
Diverse transformation
O
Nu
N
Iron catalysis
Hypervalent iodine reagents (HIRs)
h
and some others,3i-l which have been found to be highly
R
Nu = N3, OPh, SPh, SCN, Br, I
Excellent group tolerance
Room temperature radical cyclization
efficient in hypervalent iodine chemistry. Otherwise, the use of
noble metal catalyst and toxic additives does not meet the
requirement in current organic synthesis. In order to address
this issue, as one of the efficient strategies, iron catalysis, have
been successfully developed in organic synthesis, which also
has achieved considerable advancement because of its
economy and low toxicity.4 To the best of our knowledge, only
a handful of work by using iron catalysis and HIRs chemistry
have been reported so far.3e-h For example, Kuninobu and
coworkers reported the first Fe(CO)3-promoted the cleavage of
IO bond within PhI(OAc)2 (PIDA), yielding the hypervalent
iodine radicals that triggered the subsequent radical addition
of alkenes (Scheme 1a).3g Our group recently realized the
selective oxidation of C(sp3)H of 2H-azirines using this
strategy (Scheme 1b).3h Based on the previous work,3 we
envisioned that this strategy can be further extended to more
challenging organic reactions.
Scheme 1. Fe-catalyzed cleavage of IO within HIRs.
heterocyclic compounds, the isoxazolines scaffold has been
found in many biological natural products, agrochemicals and
pharmaceuticals, natural and artificial products,5a-f as well as
serving as chiral ligand in asymmetric catalysis.5g-h Massive
research effort in past years has been devoted to isoxazoline
synthesis, including transition metal catalysis and metal-free
strategies.6 Particularly, oximes bearing unactivated carbon-
carbon double bond used as the precursor has been reported
for its ability to access isoxazolines.7 For an early example,
Han’s group realized the oxime radical promoted
dioxygenation, oxyamination, and diamination of alkenes via
the cyclization of α,ß-unsaturated oximes in the presence of
equivalent of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) as
the promoter, delivering a series of isoxazolines and cyclic
nitrones.7a Then, the cyclizations of oximes using nucleophiles
such as carbon, nitrogen oxygen, and some others via varied
reaction modes demonstrated the powerful ability of this
synthetic strategy.6-7 Despite of these advances, most of the
cyclizations are heavily restricted by the coordinating ability of
hydroxyl unit, susceptibility toward oxygen (air), and excessive
use of metal catalyst or external additives. Additionally, the
late-stage transformation of the cyclization product is
extremely important but not easy to fulfil in most cases.8 In
As one of the most valuable five-membered N-containing
a. Department of Chemistry, Huaibei Normal University, Huaibei, Anhui 235000, P.R.
China; Fax: (+86)-561-309-0518; phone: (+86)-561-380-2069; e-mail:
hongjili@chnu.edu.cn; leiwang@chnu.edu.cn
b. State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Science, Shanghai 20032, P. R. China
† Footnotes relating to the title and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
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Organic & Biomolecular Chemistry
Table 1. Optimization of the reaction conditions.a
Table 2. The scope of oximes.a
View Article Online
DOI: 10.1039/C9OB02424G
OH
N
OH
O
OH
I
OTs
N
N
OH
I
O
OTs
N
Fe(acac)2 (5 mol%)
DCM, rt, air, 6 h
OTs
Fe source (5 mol%)
Solvent, rt, air, 6 h
R
Ph
R
Ph
OTs
Ph
3b
1
2a
3a b
1a
2a
O
O
OTs
Et
OTs
OTs
N
N
O
OTs
N
Entry
1
2
3
4
5
6
7
8
Fe source

Fe(acac)2
FeCl2
FeBr2
FeSO4
Solvent
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
CH3OH
Acetone
CH3CN
CHCl3
PhMe
DCE
Yield (%)b
14
Me
3c
c
, 75%
O
3b
3a
, 78%
3a
, 80%,78%
81
30
32
17
45
20
28
17
Trace
32
35
51
65
N
O
O
N
O
N
OTs
OTs
N
OTs
Cl
3g
, 88%
O
3d
, 77%
t-Bu
MeO
3f
3e
, 76%
O
i-Pr
Br
, 73%
Fe(acac)3
FeCl3
OTs
N
O
OTs
MeO
N
N
OTs
OTs
OTs
O
N
N
OTs
Me
Fe(OAc)3
Fe(acac)2
Fe(acac)2
Fe(acac)2
Fe(acac)2
Fe(acac)2
Fe(acac)2
Fe(acac)2
Fe(acac)2
Fe(acac)2
Fe(acac)2
Fe(acac)2
NC
3k
3i
, 72%
O
, 81%
O
3j
, 74%
O
3h
, 86%
O
9
10
11
12
13
14
15
16
17
18
19
OTs
OTs
OTs
OTs
OMe
N
OTs
Cl
N
N
Br
F
3o
, 44%
O
3l
, 72%
O
3n
, 83%
3m
, 81%
O
O
N
OTs
N
N
OTs
Me
N
MeO
Cl
Cl
Cl
THF
47
DCM
DCM
DCM
DCM
80c
82d
81e
75f
Me
3s
, 70%
O
3p
, 89%
3q
,71%
O
3r
, 87%
OMe
Cl
O
O
OTs
N
OTs
N
N
OTs
N
Me
aReaction conditions: Fe source (5 mol%), 1a (0.20 mmol), 2a (0.25 mmol) and
distilled solvent (1.0 mL) at room temperature under air for 6 h. bIsolated yield.
cN2. dDCM (anhydrous). e7 h. f5 h.
3u
3v
, 65%
, 49%
3w
, 67%
3t
, 73%
aReaction conditions: Fe(acac)2 (5 mol%), 1 (0.2 mmol), 2a (0.25 mmol) and
DCM (1 mL) at room temperature under air for 6 h. b Isolated yield. c gram-
scale reaction.
this respect, exploration of mild approaches for highly efficient
construction of structurally diverse isoxazolines under
environment-benign reaction conditions is still highly
desirable.
Herein, we will detail recent findings in our group with
respect to the hypervalent iodine chemistry.3h,9 Unlike the
previous work on the oxidation of saturated C–H using PIDA,3h
it is worth mentioning that a highly active sulfonyloxyl radical
generated from Koser’s HIRs using iron catalysis at room
temperature is the key to the success of the radical cyclization
of oximes, and which can be easily incorporated into the final
products isoxazolines, therefore facilitating their late-stage
transformations (Scheme 1c).
indicated that only slightly enhanced yield of 3a was achieved
(entries 6–8). Following that, some typical organic solvents
were tested in the cyclization of 1a with 2a by using Fe(acac)2
as a catalyst. Obviously, the use of methanol led to the
formation of 3a in 17% yield (entry 9). Even worse was only
trace amount of 3a was observed when using acetone as a
solvent (entry 10). Performing the model reaction in CH3CN or
CHCl3 did not enhance the isolated yield of 3a (entries 11 and
12). The employment of toluene and 1,2-dichloroethane (DCE)
led to the formation of 3a in 51% and 65% yield, respectively
(entries 13 and 14). Unfortunately, the employment of
tetrahydrofuran (THF) did not achieve improved yield (entry
15). When the reaction was carried out under nitrogen
atmosphere, comparable yield of 3a was obtained (entry 2 vs
entry 16). The reaction still proceeded in anhydrous DCM, and
generated 82% yield of 3a (entry 17). Finally, the optimization
of reaction time indicated that the model reaction almost
completed in 6 h, and produced 3a in satisfactory yield (entries
18 and 19).
After that, a number of oximes bearing different aryl groups
were used to react with 2a, affording the isoxazolines in varied
yields (Table 2). Remarkably, electron-rich group at the para-
position of phenyl ring within oximes, such as Me, Et, i-Pr, t-Bu
and MeO, are well tolerated and afforded the desired products
in moderate yields (3b3f). The incorporation of halogens,
including Cl and Br into the substrates gave the increasing
yields of products when compared with those of the formers
(3g and 3h). Oximes with meta-substitution on phenyl ring
Results and discussion
We then began the work by optimizing the reaction conditions
based on previously established catalytic radical chemistry
involving hypervalent iodine reagents.3h Using oxime 1a and
hypervalent iodine reagent 2a as reaction substrates, and
using dichloromethane (DCM) as reaction medium, it is
observed that the product 3a was achieved in 14% isolated
yield, and further confirmed by the single-crystal structure
analysis (Table 1, entry 1).10 Encouraged by this finding, we
then employed Fe(acac)2 as a catalyst to improve the radical
cyclization, which could produce 3a in 81% yield (entry 2).
Furthermore, the use of some other iron(II) salts, including
FeCl2, FeBr2 and FeSO4, failed to improve the radical process
(entries 3–5). We then continued to examined the iron(III)
salts, such as Fe(acac)3, FeCl3 and Fe(OAc)3, and which
2 | Organic & Biomolecular Chemistry, 2019, 00, 1-3
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Organic & Biomolecular Chemistry
ARTICLE
Table 3. The scope of Koser’s reagents. a
View Article Online
O
Br
N
O
OPh
SPh
SCN
N
N
N
NaBr
DOI: 10.1039/C9OB02424G
PhONa
OH
OH
O
Ph
N
O
O
acetone, 80 ºC, 8 h
5d, 80%
N
O
S
R
Ph
Ph
Ph
acetone, 80 ºC, 6 h
I
Fe(acac)2 (5 mol%)
DCM, rt, air, 6 h
5a
, 76%
Ph
O
S
R
O
Ph
O
I
Ph
N
O
OTs
O
N
1a
4b
O
NaI
2
PhSNa
Ph
Ph
Ph
acetone, 80 ºC, 10 h
acetone, 80 ºC, 6 h
5e
, 95%
Me
O
S
5b
, 89%
3a
O
R1
O
O
N3
N
O
O
O
O
O
O
N
NaN3
N
Me
O
S
KSCN
N
N
S
S
O
O
O
acetone, 80 ºC, 8 h
Ph
DMF, 80 ºC, 10 h
Ph
Ph
Ph
5f
, 89%
4b
4 4c
4-ClC6H4
3-NO2C6H
, 85%
, 90%
5c
, 86%
4a
, 82%
4d
, 79%
Scheme 2. Diverse transformations of 3a.
Me
O
O
O
S
O
O
O
O
O
O
O
N
N
S Me
HIRs including PIDA3m-n and Togni’s reagent were not reactive
under the optimal conditions (Table 4), further indicating the
unique activity of Koser’s reagent.
O
O
Ph
Ph
Me
c
4e
, 80%
4g
, 66%
4f
, 75%
aReaction conditions: Fe(acac)2 (5 mol%), 1a (0.20 mmol), 2 (0.25 mmol) and DCM
(1 mL) at room temperature under air for 6 h. bIsolated yield. c15 h.
The TsO group belongs to an extremely good leaving
group in organic synthesis, which can be attacked by many
kinds of nucleophiles to realize diverse transformations.
Therefore, product 3a was selected as a representative
example for the following investigation (Scheme 2). The
experiment results indicate that the nucleophiles including
PhONa, PhSNa, KSCN, NaBr and NaI, can readily enable the
produced the relating products in acceptable yields (3i-n). In
the case of the ortho-substituted substrate, only 44% yield of
3o was obtained under the above optimal conditions, showing
that strong steric hindrance existed in this reaction system (3f
vs 3o). Furthermore, the oximes bearing disubstitution on
phenyl ring were employed as substrates to react with 2a,
moderate yields (7089%) were achieved (3p3s). Reactions
with oxime possessing π-conjugated group gave the regarding
product in 73% yield (3t). We then found that the oximes with
alky group including Bn and Cy showed lower reactivity under
optimal reaction conditions, generating desired products in
65% (3u) and 49% (3v) yield, respectively. Particularly, a steric
oxime, (E)-3-methyl-1-phenylbut-3-en-1-one oxime, also
efficiently react with 2a to afford the cyclization product 3w in
67% isolated yield. Notably, the reaction to form 3a was
allowed to be performed on a gram-scale, albeit with a slightly
reduced yield (78%).
We continued to examine several Koser’s HIRs, and which
were then subjected to the cyclization of oxime 2a under the
optimal reaction conditions. Substitution on the benzene ring
of HIRs was tolerated (Table 3). It was found that HIRs with
electron-withdrawing group, such as Cl and NO2, delivered the
desired products in good yields (4b and 4c). Installation of
Methyl group both at the ortho- and meta-position was also
allowed to react with 1a, affording the relating products 4d
and 4e in 79% and 80% yield, respectively. The reaction of HIRs
having naphthyl group with 1a proceeded smoothly to give 4f
in decreasing yield. Finally, hydroxy(phenyl)-ƛ3-iodanyl
methanesulfonate was evaluated and the methanesulfonyl
group could be built into the product 4g with 66% isolated
yield. Unfortunately, we further found that some other typical
o
substitution of TsO group using acetone as solvent at 80 C,
generating the according products (5a5e) in good yields. In
the case of NaN3, the reaction of 3a proceeded well in DMF
under mild conditions, and afforded 5f in 89% yield.
Next, some experiments were carried out to disclose the
possible reaction pathway (Scheme 3). At first, 2.0 equiv. of
radical scavenger TEMPO was directly added into the reaction
1a with 2a, and which proceeded under the optimal condition
for 6 h (Scheme 3a). After that, only compound 6 was isolated
in 92% yield and no 3a was detected at all, showing that a
radical cyclization was involved in the catalytic cycle (Scheme
4). The model reaction that carried out under O2 atmosphere
in freshly distilled DCM gave 78% yield of 3a and trace amount
of 3a-OH11, indicating that oxygen molecular does not affect
this radical cyclization (Scheme 3b, eq. 1). Furthermore,
performing the reaction 1a with 2a in DCM/H2O (V/V = 1:1)
obtain the mixture of 3a/3a-OH with a ratio of 3:4 (Scheme 3b,
eq. 2). Following that, we found the transformation of 3a into
3a-OH almost did not proceed in DCM/H2O (V/V = 1:1)
TEMPO experiment
(a)
OH
N
TEMPO ( 2.0 equiv)
Fe(acac)2 (5 mol%)
OH
O
OTs
O
N
O
N
N
I
Ph
(b)
Ph
OTs
Ph
Ph
OTs
OTs
DCM, rt, air, 6 h
1a
3a
, 0%
2a
6
, 92%
Control experiment
OH
N
OH
I
Table 4. Radical cyclization of oxime 1a with HIRs.
O
N
O
OH
N
Fe(acac)2 (5 mol%)
Ph
Ph
Ph
OTs
(eq 1)
(eq 2)
Ph
Ph
DCM, O2 (balloon)
rt, 6 h
Ph
OH
N
O
1a
2a
R
N
3a
, 73%
3a-
OH, trace
Fe(acac)2 (5 mol%)
DCM, rt, air, 6 h
Ph
HIRs
OH
Ph
I
OH
I
N
O
N
O
N
OH
Fe(acac)2 (5 mol%)
3
1a
2
OTs
Ph
DCM/H2O (v/v = 1:1)
rt, air, 6 h
Ph
CF3
O
2a
1a
3a
, 32%
3a-
OH, 44%
OH
I
3a 3a
:
-OH = 3:4
I(OAc)2
PIDA
HIRs:
Ph
OTs
O
OTs
N
O
O
OH
N
Fe(acac)2 (5 mol%)
Koser's reagent
(eq 3)
Togni's reagent II
Ph
Ph
DCM/H2O (v/v = 1:1)
rt, air, 24 h
3a
3a-
OH, trace
3a
3-CF
3, 0%
, 80%
3-OAc
, 0%
Scheme 3. Mechanistic investigation.
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Organic & Biomolecular Chemistry
mass spectroscopy data of the products were collected on an
Agilent Technologies 6540 UHD Accurate-Mass Q-TOF LC/MS (ESI)
and a Thermo Fisher Scientific LTQ FTICR-MS instrument. Melting
points were determined in open capillary tube using WRS-1B digital
melting point apparatus. All the solvents in this cyclization reaction
were freshly distilled prior to use.
View Article Online
DOI: 10.1039/C9OB02424G
OH
I
O
O
OTs
N
N
3a
Ph
OTs
Ph
Ph
2a
Fe(II)
H2O
OTs PhI
OTs
O
N
Fe(III)
A
Ph
OH
D
C
Trapped by TEMPO
OH
HO Fe(III)
General procedure for the synthesis of 3a
N
O
N
O
1a
N
OH
N
Ph
A 10 mL reaction tube was charged with (E)-1-phenylbut-3-en-
1-one oxime (1a, 32.2 mg, 0.20 mmol), Fe(acac)2 (2.5 mg, 5 mol%),
DCM (1.0 mL) and [hydroxy(tosyloxy)iodo]benzene (2a, 98.1 mg,
0.25 mmol) was added to the resulted mixture. The reaction tube
was placed at room temperature and stirred for 6 h. Then, the
mixture in reaction tube was detected by TLC. After the reaction
was completed, distilled water (10 mL) was added into the mixture,
and extracted with dichloromethane (DCM, 3×10 mL). The organic
layers were combined, dried over Na2SO4, and concentrated under
reduced pressure to yield the crude product, which was purified by
flash chromatography (silica gel, petroleum ether/ethyl acetate =
3:1 to 9:1), affording the desired product 3a as a white solid (53.0
mg, 80% yield).
B
Ph
6
Ph
Scheme 4. Proposed reaction mechanism.
(Scheme 3b, eq. 3). These experimental results show the
presence of water would affect the formation of 3a.
Based on these results and previous reports,3 a plausible
mechanism for this iron(II) catalyzed cyclization is depicted in
Scheme 4. Firstly, the oxidization of iron(II) by 2a afforded
species iron(III) A3g-h,12 and the reactive radical p-
toluenesulfonyloxyl radical TsO. Then oxime 1a coordinated
with A by hydroxyl group to complex B, which underwent a
single electron transfer to generate iron(II) and a highly
reactive species C. Then an intramolecular radical cyclization of
C generated intermediate D that could be trapped by radical
scavenger TEMPO to obtain 6.7a,11,13 Finally the radical coupling
of TsO with D delivered the product 3a.
O
OTs
N
(3-Phenyl-4,5-dihydroisoxazol-5-yl)methyl
4-
Conclusions
methylbenzenesulfonate (3a): White solid; 53.0 mg, 80% yield; 1H
NMR (600 MHz, CDCl3) δ 7.79 (d, J = 8.4 Hz, 2H), 7.63–7.61 (m, 2H),
7.44–7.38 (m, 3H), 7.34 (d, J = 7.8 Hz, 2H), 4.96–4.91 (m, 1H), 4.17–
4.10 (m, 2H), 3.44 (dd, J = 16.8, 10.8 Hz, 1H), 3.24 (dd, J = 16.8, 7.2
Hz, 1H), 2.44 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 156.2, 145.2,
132.4, 130.4, 129.9, 128.8, 128.7, 128.0, 126.7, 77.4, 69.2, 37.3,
21.6. HRMS (ESI) ([M+H]+) Calcd. For [C17H18NO4S]+: 332.0951,
Found: 332.0949.
In summary, an iron(II)-catalyzed cyclization of oximes with
HIRs at room temperature via a single electron transfer
process has been developed, which provides an expedient
access to isoxazolines. The current work using iron catalysis
and hypervalent iodine chemistry complements the literature
protocol,
wherein
a
readily
transformable
p-
toluenesulfonyloxyl group was incorporated into the target
products in one-pot. The late-stage transformations of
cyclization products have proved their practical applications in
organic synthesis. Although a possible radical pathway for this
iron-catalyzed cyclization was proposed, another reaction
model via hypervalent iodine activated the double bond was
not fully ruled out. The further exploration of this strategy in
synthetic chemistry and mechanistic studies is underway in our
laboratory.
O
OTs
N
Me
(3-(p-Tolyl)-4,5-dihydroisoxazol-5-yl)methyl
4-
methylbenzenesulfonate (3b): White solid; 53.9 mg, 78% yield; 1H
NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.4 Hz, 2H), 7.50 (d, J = 8.0 Hz,
2H), 7.34 (d, J = 8.0 Hz, 2H), 7.20 (d, J = 8.0 Hz, 2H), 4.94–4.87 (m,
1H), 4.16–4.08 (m, 2H), 3.42 (dd, J = 17.2, 10.8 Hz, 1H), 3.21 (dd, J =
16.8, 6.8 Hz, 1H), 2.44 (s, 3H), 2.38 (s, 3H). 13C NMR (101 MHz,
CDCl3) δ 156.2, 145.2, 140.7, 132.5, 129.9, 129.4, 128.0, 126.7,
126.0, 77.2, 69.2, 37.4, 21.6, 21.4. HRMS (ESI) ([M+H]+) Calcd. For
[C18H20NO4S]+: 346.1108, Found: 346.1108.
Conflicts of interests
There are no conflicts to declare.
Experimental section
1
General: All H NMR and 13C NMR spectra were recorded on a 400
O
MHz (or 600 MHz) Bruker FT-NMR spectrometers 400 MHz (or 600
MHz) and 100 MHz (or 150 MHz), respectively). All chemical shifts
are given as δ value (ppm) with reference to tetramethylsilane
(TMS) as an internal standard. The peak patterns are indicated as
follows: s, singlet; d, doublet; t, triplet; m, multiplet; q, quartet. The
coupling constants, J, are reported in Hertz (Hz). High resolution
OTs
N
Et
4 | Organic & Biomolecular Chemistry, 2019, 00, 1-3
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Organic & Biomolecular Chemistry
Organic & Biomolecular Chemistry
ARTICLE
O
OTs
(3-(4-Ethylphenyl)-4,5-dihydroisoxazol-5-yl)methyl
4-
N
View Article Online
DOI: 10.1039/C9OB02424G
1
methylbenzenesulfonate (3c): White solid; 53.9 mg, 75% yield; H
NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.4 Hz, 2H), 7.53 (d, J = 8.4 Hz,
2H), 7.34 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 4.95–4.88 (m,
1H), 4.16–4.08 (m, 2H), 3.42 (dd, J = 16.8, 10.4 Hz, 1H), 3.22 (dd, J =
16.8, 6.8 Hz, 1H), 2.67 (q, J = 7.6 Hz, 2H), 2.44 (s, 3H), 1.25 (t, J = 7.6
Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 156.2, 147.0, 145.2, 132.4,
129.9, 128.3, 128.0, 126.8, 126.2, 77.2, 69.2, 37.4, 28.8, 21.6, 15.3.
HRMS (ESI) ([M+H]+) Calcd. For [C19H22NO4S]+: 360.1264, Found:
360.1264.
Cl
(3-(4-Chlorophenyl)-4,5-dihydroisoxazol-5-yl)methyl
4-
1
methylbenzenesulfonate (3g): White solid; 64.4 mg, 88% yield; H
NMR (400 MHz, CDCl3) δ 7.78 (d, J = 8.0 Hz, 2H), 7.55 (d, J = 8.8 Hz,
2H), 7.38–7.33 (m, 4H), 4.98–4.91 (m, 1H), 4.17–4.11 (, 2H), 3.41
(dd, J = 16.8, 10.8 Hz, 1H), 3.22 (dd, J = 16.8, 6.8 Hz, 1H), 2.44 (s,
3H). 13C NMR (100 MHz, CDCl3) δ 155.3, 145.2, 136.4, 132.5, 129.9,
129.0, 128.0, 127.9, 127.4, 77.7, 69.1, 37.1, 21.6. HRMS (ESI)
([M+H]+) Calcd. For [C17H17ClNO4S]+: 366.0561, Found: 366.0561.
O
OTs
N
O
OTs
N
i-Pr
(3-(4-Isopropylphenyl)-4,5-dihydroisoxazol-5-yl)methyl
4-
1
Br
methylbenzenesulfonate (3d): White solid; 57.5 mg, 77% yield; H
NMR (400 MHz, CDCl3) δ 7.78 (d, J = 8.4 Hz, 2H), 7.54 (d, J = 8.0 Hz,
2H), 7.33 (d, J = 8.0 Hz, 2H), 7.27–7.25 (m, 2H), 4.94–4.87 (m, 1H),
4.15–4.07 (m, 2H), 3.42 (dd, J = 16.8, 10.4 Hz, 1H), 3.22 (dd, J = 16.8,
6.8 Hz, 1H), 2.98–2.88 (m, 1H), 2.43 (s, 3H), 1.26 (d, J = 6.8 Hz, 6H).
13C NMR (100 MHz, CDCl3) δ 156.1, 151.6, 145.1, 132.5, 129.9,
128.0, 126.8, 126.3, 77.2, 69.2, 37.4, 34.0, 23.7, 21.6. HRMS (ESI)
([M+H]+) Calcd. For [C20H24NO4S]+: 374.1421, Found: 374.1422.
(3-(4-Bromophenyl)-4,5-dihydroisoxazol-5-yl)methyl
4-
1
methylbenzenesulfonate (3h): White solid; 70.6 mg, 86% yield; H
NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.0 Hz, 2H), 7.53–7.32 (m, 4H),
7.33 (d, J = 8.0 Hz, 2H), 4.97–4.90 (m, 1H), 4.19–4.08 (m, 2H), 3.41
(dd, J = 17.2, 11.2 Hz, 1H), 3.21 (dd, J = 17.2, 7.2 Hz, 1H), 2.44 (s,
3H). 13C NMR (100 MHz, CDCl3) δ 155.4, 145.2, 132.4, 131.9, 129.9,
128.1, 127.9, 127.8, 124.6, 77.8, 69.1, 36.9, 21.6. HRMS (ESI)
([M+H]+) Calcd. For [C17H17BrNO4S]+: 410.0056, Found: 410.0056.
O
OTs
N
O
OTs
N
t-Bu
NC
(3-(4-(tert-Butyl)phenyl)-4,5-dihydroisoxazol-5-yl)methyl
4-
1
methylbenzenesulfonate (3e): White solid; 56.6 mg, 73% yield; H
NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.4 Hz, 2H), 7.55 (d, J = 8.4 Hz,
2H), 7.42 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 4.95–4.88 (m,
1H), 4.15–4.07 (m, 2H), 3.43 (dd, J = 17.2, 10.8 Hz, 1H), 3.23 (dd, J =
17.2, 6.8 Hz, 1H), 2.44 (s, 3H), 1.33 (s, 9H). 13C NMR (100 MHz,
CDCl3) δ 156.1, 153.9, 145.1, 132.5, 129.9, 128.0, 126.6, 126.0,
125.7, 77.2, 69.2, 37.5, 34.9, 31.1, 21.6. HRMS (ESI) ([M+H]+) Calcd.
For [C21H26NO4S]+: 388.1577, Found: 388.1578.
(3-(4-cyanophenyl)-4,5-dihydroisoxazol-5-yl)methyl
4-
1
methylbenzenesulfonate (3i): White solid; 57.7 mg, 81% yield; H
NMR (600 MHz, CDCl3) δ 7.77 (d, J = 7.8 Hz, 2H), 7.73 (d, J = 8.4 Hz,
2H), 7.68 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 7.8 Hz, 2H), 5.03–4.98 (m,
1H), 4.21–4.13 (m, 2H), 3.45 (dd, J = 16.8, 11.0 Hz, 1H), 3.27 (dd, J =
16.9, 7.0 Hz, 1H), 2.45 (s, 3H). NMR (150 MHz, CDCl3) δ: 155.0,
145.3, 133.1, 132.4, 132.2, 129.9, 127.9, 127.1, 118.1, 113.6, 78.4,
69.0, 36.4, 21.6. HRMS (ESI) ([M+H]+) Calcd. For [C18H16N2O4S]+:
357.0904, Found: 357.0904.
O
OTs
N
O
OTs
N
Me
MeO
(3-(4-Methoxyphenyl)-4,5-dihydroisoxazol-5-yl)methyl
4-
1
methylbenzenesulfonate (3f): White solid; 54.9 mg, 76% yield; H
NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 8.4 Hz,
2H), 7.34 (d, J = 8.0 Hz, 2H), 6.91 (d, J = 8.8 Hz, 2H), 4.93–4.86 (m,
1H), 4.18–4.07 (m, 2H), 3.84 (s, 3H), 3.42 (dd, J = 16.8, 10.8 Hz, 1H),
3.22 (dd, J = 16.8, 6.8 Hz, 1H), 2.44 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 161.3, 155.8, 145.2, 130.0, 128.3, 128.0, 121.4, 114.2, 77.1,
69.2, 55.4, 37.6, 21.7. HRMS (ESI) ([M+H]+) Calcd. For [C18H20NO5S]+:
362.1057, Found: 362.1058.
(3-(m-Tolyl)-4,5-dihydroisoxazol-5-yl)methyl
4-
1
methylbenzenesulfonate (3j): White solid; 51.1 mg, 74% yield; H
NMR (600 MHz, CDCl3) δ 7.79 (d, J = 8.4 Hz, 2H), 7.45 (s, 1H), 7.40
(d, J = 7.2 Hz, 1H), 7.34 (d, J = 7.8 Hz, 2H), 7.29 (t, J = 7.8 Hz, 1H),
7.23 (d, J = 7.8 Hz, 1H), 4.94–4.90 (m, 1H), 4.18–4.07 (m, 2H), 3.43
(dd, J = 17.4, 10.8 Hz, 1H), 3.24 (dd, J = 16.8, 6.6 Hz, 1H), 2.44 (s,
3H), 2.37 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 156.3, 145.2, 138.5,
132.4, 131.2, 129.9, 128.7, 128.6, 127.3, 123.9, 77.3, 69.2, 37.4,
21.6, 21.3. HRMS (ESI) ([M+H]+) Calcd. For [C18H20NO4S]+: 346.1108,
Found: 346.1109.
This journal is © The Royal Society of Chemistry 20xx
Organic & Biomolecular Chemistry, 2019, 00, 1-3 | 5
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Organic & Biomolecular Chemistry
Page 6 of 11
ARTICLE
Organic & Biomolecular Chemistry
O
OTs
133.2, 132.3, 130.8, 130.2, 129.9, 129.6, 127.9, 125.2, 122.8, 77.8,
N
View Article Online
+
69.1, 36.8, 21.6. HRMS (ESI) ([M+H]+) CalDcdO.I:F1o0r.10[3C917/CH917OCBlN02O442S4]G:
MeO
410.0056, Found: 410.0057.
O
OTs
OMe N
(3-(3-Methoxyphenyl)-4,5-dihydroisoxazol-5-yl)methyl
4-
1
methylbenzenesulfonate (3k): White solid; 52.0 mg, 72% yield; H
NMR (600 MHz, CDCl3) δ 7.78 (d, J = 7.8 Hz, 2H), 7.34 (d, J = 8.4 Hz,
2H), 7.30 (t, J = 8.4 Hz, 1H), 7.21–7.20 (m, 1H), 7.13 (d, J = 7.8 Hz,
1H), 6.98–6.96 (m, 1H), 4.95–4.90 (m, 1H), 4.19–4.10 (m, 2H), 3.82
(s, 3H), 3.42 (dd, J = 16.8, 10.8 Hz, 1H), 3.21 (dd, J = 16.8, 6.6 Hz,
1H), 2.44 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 159.7, 156.2, 145.2,
132.4, 130.0, 129.9, 129.7, 127.9, 119.4, 116.7, 111.4, 77.5, 69.2,
(3-(2-Methoxyphenyl)-4,5-dihydroisoxazol-5-yl)methyl
4-
methylbenzenesulfonate (3o) White solid; 31.8 mg, 44% yield; δ 1H
NMR (600 MHz, CDCl3) δ 7.78 (d, J = 8.4 Hz, 2H), 7.65–7.63 (m, 1H),
7.38–7.36 (m, 1H), 7.32 (d, J = 8.4 Hz, 2H), 6.96–6.91 (m, 2H), 4.88–
55.3, 37.3, 21.6. HRMS (ESI) ([M+H]+) Calcd. For [C18H20NO5S]+: 4.83 (m, 1H), 4.14–4.06 (m, 2H), 3.83 (s, 3H), 3.54 (dd, J = 17.4, 10.8
Hz, 1H), 3.32 (dd, J = 18.0, 6.6 Hz, 1H), 2.42 (s, 3H). 13C NMR (150
MHz, CDCl3) δ 157.4, 155.7, 145.0, 132.4, 131.5, 129.8, 129.3, 127.8,
120.7, 117.9, 111.3, 77.2, 69.5, 55.4, 39.8, 21.5. HRMS (ESI)
([M+H]+) Calcd. For [C18H20NO5S]+: 362.1057, Found: 362.1057.
362.1057, Found: 362.1057.
O
OTs
N
F
O
OTs
N
Cl
Cl
(3-(3-fluorophenyl)-4,5-dihydroisoxazol-5-yl)methyl
4-
1
methylbenzenesulfonate (3l): White solid; 50.3 mg, 72% yield; H
NMR (600 MHz, CDCl3) δ 7.78 (d, J = 8.4 Hz, 2H), 7.39–7.32 (m, 5H),
7.15–7.09 (m, 1H), 4.97–4.93 (m, 1H), 4.20–4.10 (m, 2H), 3.41 (dd, J
= 16.8, 10.8 Hz, 1H), 3.21 (dd, J = 16.8, 6.6 Hz, 1H), 2.44 (s, 3H).
NMR (150 MHz, CDCl3) δ: 162.67 (d, J = 245.3 Hz), 155.36 (d, J =
245.3 Hz), 145.3, 132.4, 130.9 (d, J = 8.3Hz), 130.4 (d, J = 8.4 Hz),
129.9, 127.9, 122.5 (d, J = 3.0 Hz), 117.3 (d, J = 21.5 Hz), 113.5 (d, J =
23.4 Hz), 77.8, 69.1, 37.0, 21.6. 19F NMR (600 MHz, CDCl3) δ: -
111.94. HRMS (ESI) ([M+H]+) Calcd. For [C17H16FNO4S]+: 350.0857,
Found: 350.0858.
(3-(3,4-Dichlorophenyl)-4,5-dihydroisoxazol-5-yl)methyl
4-
1
methylbenzenesulfonate (3p): White solid; 71.2 mg, 89% yield; H
NMR (400 MHz, CDCl3) δ 7.78 (d, J = 8.0 Hz, 2H), 7.67 (s, 1H), 7.49–
7.46 (m, 2H), 7.34 (d, J = 8.0 Hz, 2H), 5.00–4.93 (m, 1H), 4.21–4.10
(m, 2H), 3.40 (dd, J = 16.8, 11.2 Hz, 1H), 3.20 (dd, J = 16.8, 6.8 Hz,
1H), 2.45 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 154.5, 145.3, 134.5,
133.1, 132.4, 130.8, 130.0, 128.8, 128.4, 127.9, 125.8, 78.1, 69.0,
36.8, 21.6. HRMS (ESI) ([M+H]+) Calcd. For [C17H16Cl2NO4S]+:
400.0172, Found: 400.0173.
O
OTs
N
O
Cl
OTs
N
Me
Me
(3-(3-Chlorophenyl)-4,5-dihydroisoxazol-5-yl)methyl
4-
1
methylbenzenesulfonate (3m): White solid; 59.3 mg, 81% yield; H
NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.0 Hz, 2H), 7.58 (s, 1H), 7.48
(d, J = 7.2 Hz, 1H), 7.39–7.31 (m, 4H), 4.98–4.92 (m, 1H), 4.20–4.11
(m, 2H), 3.40 (dd, J = 16.8, 10.8 Hz, 1H), 3.19 (dd, J = 16.8, 6.8 Hz,
1H), 2.44 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 155.1, 145.2, 134.6,
132.3, 130.5, 130.2, 129.9, 129.8, 127.8, 126.6, 124.7, 77.8, 69.2,
36.7, 21.5. HRMS (ESI) ([M+H]+) Calcd. For [C17H17ClNO4S]+:
366.0561, Found: 366.0561.
(3-(3,4-Dimethylphenyl)-4,5-dihydroisoxazol-5-yl)methyl
4-
1
methylbenzenesulfonate (3q): White solid; 51.0 mg, 71% yield; H
NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.4 Hz, 2H), 7.41 (s, 1H), 7.35–
7.31 (m, 3H), 7.15 (d, J = 7.6 Hz, 1H), 4.93–4.86 (m, 1H), 4.18–4.14
(m, 2H), 3.42 (dd, J = 16.8, 10.8 Hz, 1H), 3.21 (dd, J = 16.8, 6.4 Hz,
1H), 2.44 (s, 3H), 2.28 (d, J = 2.8 Hz, 6H). 13C NMR (100 MHz, CDCl3)
δ 156.3, 145.1, 139.4, 137.0, 132.5, 129.9, 128.0, 127.8, 126.3,
124.3, 77.2, 69.3, 37.5, 21.6, 19.7, 19.6. HRMS (ESI) ([M+H]+) Calcd.
For [C19H22NO4S]+: 360.1264, Found: 360.1262.
O
OTs
N
Br
O
OTs
N
Cl
(3-(3-Bromophenyl)-4,5-dihydroisoxazol-5-yl)methyl
4-
Cl
1
methylbenzenesulfonate (3n): White solid; 68.1 mg, 83% yield; H
NMR (600 MHz, CDCl3) δ 7.77 (d, J = 8.4 Hz, 2H), 7.74 (s, 1H), 7.53
(d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.4 Hz, 2H), 7.26 (t, J = 7.2 Hz, 1H),
4.97–4.92 m, 1H), 4.19–4.10 (m, 2H), 3.42–3.37 (m, 1H), 3.21–3.17
(m, 1H), 2.44 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 155.1, 145.2,
(3-(3,5-Dichlorophenyl)-4,5-dihydroisoxazol-5-yl)methyl
4-
1
methylbenzenesulfonate (3r): White solid; 69.6 mg, 87% yield; H
NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.0 Hz, 2H), 7.47–7.46 (m, 2H),
7.39–7.34 (m, 3H), 5.00–4.94 (m, 1H), 4.20–4.11 (m, 2H), 3.38 (dd, J
6 | Organic & Biomolecular Chemistry, 2019, 00, 1-3
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Organic & Biomolecular Chemistry
Organic & Biomolecular Chemistry
ARTICLE
= 16.8, 11.2 Hz, 1H), 3.18 (dd, J = 16.8, 6.8 Hz, 1H), 2.45 (s, 3H). 13C
NMR (100 MHz, CDCl3) δ 154.3, 145.3, 135.4, 132.4, 131.7, 130.0,
129.9, 127.9, 125.0, 78.2, 69.0, 36.5, 21.6. HRMS (ESI) ([M+H]+)
Calcd. For [C17H16Cl2NO4S]+: 400.0172, Found: 400.0172.
1.82–1.76 (m, 4H), 1.69 (d, J = 12.6 Hz, 1H), 1.33–1.19V(iemw,A5rtHic)le. ONnMlinRe
DOI: 10.1039/C9OB02424G
(150 MHz, CDCl3) δ: 162.4, 145.1, 132.5, 129.9, 128.0, 75.8, 69.4,
37.7, 37.0, 30.3, 30.2, 25.7, 25.6, 21.6. HRMS (ESI) ([M+H]+) Calcd.
For [C17H23NO4S]+: 338.1421, Found: 338.1422.
O
OTs
N
O
OTs
N
MeO
Me
OMe
(5-Methyl-3-phenyl-4,5-dihydroisoxazol-5-yl)methyl
4-
1
(3-(3,5-Dimethoxyphenyl)-4,5-dihydroisoxazol-5-yl)methyl
4-
methylbenzenesulfonate (3w): White solid; 46.3 mg, 67% yield; H
NMR (600 MHz, CDCl3) δ 7.78–7.77 (m, 2H), 7.60–7.58 (m, 2H),
7.41–7.37 (m, 3H), 7.32 (d, J = 7.8 Hz, 2H), 4.01 (d, J = 2.4 Hz, 2H),
3.38 (d, J = 16.8 Hz, 1H), 3.05 (d, J = 16.8 Hz, 1H), 2.43 (s, 3H), 1.48
(s, 3H). 13C NMR (150 MHz, CDCl3) δ 156.4, 145.2, 132.4, 130.2,
129.9, 129.2, 128.7, 128.0, 126.6, 84.4, 72.2, 43.0, 22.9, 21.6. HRMS
(ESI) ([M+H]+) Calcd. For [C18H20NO4S]+: 346.1108, Found: 346.1109.
1
methylbenzenesulfonate (3s): White solid; 54.8 mg, 70% yield; H
NMR (400 MHz, CDCl3) δ 7.78 (d, J = 8.0 Hz, 2H), 7.34 (d, J = 8.0 Hz,
2H), 6.75–6.74 (m, 2H), 6.50 (s, 1H), 4.95–4.88 (m, 1H), 4.19–4.06
(m, 2H), 3.40 (dd, J = 16.8, 10.8 Hz, 1H), 3.17 (dd, J = 16.8, 6.4 Hz,
1H), 2.44 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 160.8, 156.2, 145.2,
132.4, 130.5, 129.9, 127.9, 104.7, 102.5, 77.5, 69.2, 55.4, 37.2, 21.6.
HRMS (ESI) ([M+H]+) Calcd. For [C19H22NO6S]+: 392.1162, Found:
392.1160.
O
O
O
N
S
O
O
Ph
OTs
N
(3-Phenyl-4,5-dihydroisoxazol-5-yl)methyl benzenesulfonate (4a):
1
White solid; 52.0 mg, 82% yield; H NMR (400 MHz, CDCl3) δ 7.92–
7.90 (m, 2H), 7.68–7.60 (m, 3H), 7.55 (t, J = 8.0 Hz, 2H), 7.42–7.37
(m, 3H), 4.98–4.91 (m, 1H), 4.22–4.11 (m, 2H), 3.45 (dd, J = 16.8,
10.8 Hz, 1H), 3.25 (dd, J = 16.8, 6.8 Hz, 1H). 13C NMR (100 MHz,
CDCl3) δ 156.2, 134.1, 130.4, 129.3, 128.7, 127.9, 126.7, 77.4, 69.4,
37.2. HRMS (ESI) ([M+H]+) Calcd. For [C16H16NO4S]+: 318.0795,
Found: 318.0794.
(3-(Naphthalen-2-yl)-4,5-dihydroisoxazol-5-yl)methyl
4-
1
methylbenzenesulfonate (3t): White solid; 55.7 mg, 73% yield; H
NMR (400 MHz, CDCl3) δ 7.90–7.77 (m, 7H), 7.54–7.49 (m, 2H), 7.30
(d, J = 8.0 Hz, 2H), 5.00–4.93 (m, 1H), 4.23–4.11 (m, 2H), 3.53 (dd, J
= 16.8, 10.8 Hz, 1H), 3.34 (dd, J = 16.8, 6.8 Hz, 1H), 2.39 (s, 3H). 13C
NMR (100 MHz, CDCl3) δ 156.3, 145.2, 134.0, 132.8, 132.4, 129.9,
128.5, 128.4, 127.9, 127.8, 127.2, 127.1, 126.7, 126.3, 123.4, 77.6,
69.2, 37.2, 21.6. HRMS (ESI) ([M+H]+) Calcd. For [C21H20NO4S]+:
382.1108, Found: 382.1108.
O
O
O
N
S
Cl
O
Ph
O
OTs
N
(3-Phenyl-4,5-dihydroisoxazol-5-yl)methyl
4-
1
chlorobenzenesulfonate (4b): White solid; 59.6 mg, 85% yield; H
NMR (400 MHz, CDCl3) δ 7.84 (d, J = 8.4 Hz, 2H), 7.62–7.60 (m, 2H),
7.51 (d, J = 8.8 Hz, 2H), 7.43–7.38 (m, 3H), 4.98–4.91 (m, 1H), 4.20–
4.15 (m, 2H), 3.46 (dd, J = 16.8, 10.8 Hz, 1H), 3.24 (dd, J = 17.2, 6.8
(3-benzyl-4,5-dihydroisoxazol-5-yl)methyl
methylbenzenesulfonate (3u): White solid; 44.9 mg, 65% yield; H
NMR (600 MHz, CDCl3) δ 7.71 (d, J = 8.4 Hz, 2H), 7.31–7.29 (m, 4H), Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 156.2 140.8, 134.0, 130.5,
7.26–7.24 (m, 1H), 7.18–7.17 (m, 2H), 4.69–4.64 (m, 1H), 3.96 (dd, J
= 4.8, 1.2 Hz, 2H), 3.62 (d, J = 2.4 Hz, 2H), 2.88 (dd, J = 17.4, 11.4 Hz,
4-
1
129.7, 129.3, 128.8, 126.7, 69.7, 37.1. HRMS (ESI) ([M+H]+) Calcd.
For [C16H15ClNO4S]+: 352.0405, Found: 352.0405.
1H), 2.64 (dd, J = 17.4, 6.6 Hz, 1H), 2.41 (s, 3H). NMR (150 MHz,
CDCl3) δ: 157.3, 144.9, 135.1, 132.2, 129.7, 128.7, 128.5, 127.7,
126.9, 76.5, 69.4, 38.3, 33.5, 21.4. HRMS (ESI) ([M+H]+) Calcd. For
[C18H19NO4S]+: 346.1108, Found: 346.1108.
NO2
O
O
O
N
S
O
Ph
O
OTs
N
(3-Phenyl-4,5-dihydroisoxazol-5-yl)methyl
3-
nitrobenzenesulfonate (4c): White solid; 65.2 mg, 90% yield; 1H
NMR (400 MHz, CDCl3) δ 8.74–8.72 (m, 1H), 8.51–8.48 (m, 1H),
8.24–8.22 (m, 1H), 7.78 (t, J = 8.0 Hz, 1H), 7.59–7.57 (m, 2H), 7.45–
7.37 (m, 3H), 4.98–4.92 (m, 1H), 4.36–4.28 (m, 2H), 3.48 (dd, J =
16.8, 10.8 Hz, 1H), 3.25 (dd, J = 16.8, 6.8 Hz, 1H). 13C NMR (100
MHz, CDCl3) δ 156.2, 148.2, 137.8, 133.4, 130.8, 130.5, 128.8, 128.5,
128.4, 126.7, 123.3, 70.6, 36.9. HRMS (ESI) ([M+H]+) Calcd. For
[C16H15N2O6S]+: 363.0645, Found: 363.0645.
(3-Cyclohexyl-4,5-dihydroisoxazol-5-yl)methyl
4-
1
methylbenzenesulfonate (3v): White solid; 33.1 mg, 49% yield; H
NMR (600 MHz, CDCl3) δ 7.79 (d, J = 7.8 Hz, 2H), 7.36 (d, J = 7.8 Hz,
2H), 4.71–4.69 (m, 1H), 4.06–3.94 (m, 2H), 3.02 (dd, J = 17.4, 10.8
Hz, 1H), 2.82 (dd, J = 17.4, 6.0 Hz, 1H), 2.45 (s, 3H), 2.37 (s, 1H),
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Organic & Biomolecular Chemistry
5-(Phenoxymethyl)-3-phenyl-4,5-dihydroisoxazole (5a):14 White
Me
O
View Article Online
DOI: 10.1039/C9OB02424G
1
solid; 38.5 mg, 76% yield; H NMR (600 MHz, CDCl3) δ 7.70–7.69 (m,
2H), 7.41–7.40 (m, 3H), 7.28 (t, J = 7.2 Hz, 2H), 6.96 (t, J = 7.2 Hz,
1H), 6.91 (d, J = 8.4 Hz, 2H), 5.13–5.08 (m, 1H), 4.17 (dd, J = 9.6, 4.8
Hz, 1H), 4.04 (dd, J = 10.2, 6.0 Hz, 1H), 3.50 (dd, J = 16.8, 10.8 Hz,
1H), 3.38 (dd, J = 16.8, 7.2 Hz, 1H). 13C NMR (150 MHz, CDCl3) δ
158.4, 156.4, 130.2, 129.5, 129.3, 128.7, 126.7, 121.3, 114.6, 78.7,
68.4, 37.6. HRMS (ESI) ([M+H]+) Calcd. For [C16H16NO2]+: 254.1176,
Found: 254.1174.
O
N
O
S
Me
O
Ph
(3-Phenyl-4,5-dihydroisoxazol-5-yl)methyl
2,4-
dimethylbenzenesulfonate (4d): White solid; 54.5 mg, 79% yield; 1H
NMR (600 MHz, CDCl3) δ 7.84 (d, J = 8.4 Hz, 1H), 7.62–7.60 (m, 2H),
7.43–7.38 (m, 3H), 7.15 (s, 1H), 7.12 (d, J = 7.8 Hz, 1H), 4.95–4.90
(m, 1H), 4.13–4.06 (m, 2H), 3.44 (dd, J = 16.8, 10.8 Hz, 1H), 3.24 (dd,
J = 16.8, 7.2 Hz, 1H), 2.59 (s, 3H), 2.37 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 156.2, 145.0, 138.4, 133.4, 130.7, 130.3, 130.1, 128.8,
128.7, 126.7, 126.6, 77.5, 69.2, 37.1, 21.3, 20.1. HRMS (ESI)
([M+H]+) Calcd. For [C18H20NO4S]+: 346.1108, Found: 346.1109.
O
SPh
N
Ph
3-Phenyl-5-((phenylthio)methyl)-4,5-dihydroisoxazole
(5b):15
1
Me
O
White solid; 47.9 mg, 89% yield; H NMR (600 MHz, CDCl3) δ 7.66–
7.64 (m, 2H), 7.42–7.39 (m, 5H), 7.32–7.29 (m, 2H), 7.24–7.22 (m,
1H), 4.89–4.84 (m, 1H), 3.45–3.35 (m, 2H), 3.26 (dd, J = 16.8, 6.6 Hz,
1H), 2.98 (dd, J = 13.8, 9.0 Hz, 1H). 13C NMR (150 MHz, CDCl3) δ
156.2, 134.7, 130.1, 130.0, 129.3, 129.1, 128.7, 126.8, 126.7, 79.5,
39.5, 37.7. HRMS (ESI) ([M+H]+) Calcd. For [C16H16NOS]+: 270.0947,
Found: 270.0946.
O
O
N
S
O
Ph
Me
(3-Phenyl-4,5-dihydroisoxazol-5-yl)methyl
2,5-
dimethylbenzenesulfonate (4e): White solid; 55.2 mg, 80% yield; 1H
NMR (600 MHz, CDCl3) δ 7.78 (s, 1H), 7.63–7.61 (m, 2H), 7.43–7.38
(m, 3H), 7.32 (d, J = 7.8 Hz, 1H), 7.23 (d, J = 7.8 Hz, 1H), 4.97–4.92
(m, 1H), 4.15–4.07 (m, 2H), 3.45 (dd, J = 16.8, 10.8 Hz, 1H), 3.26 (dd,
J = 16.8, 6.6 Hz, 1H), 2.58 (s, 3H), 2.37 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 156.2, 136.2, 135.4, 134.7, 133.4, 132.6, 130.4, 130.3,
128.8, 128.7, 126.7, 77.5, 69.2, 37.2, 20.7, 19.7. HRMS (ESI)
([M+H]+) Calcd. For [C18H20NO4S]+: 346.1108, Found: 346.1109.
O
SCN
N
Ph
3-Phenyl-5-(thiocyanatomethyl)-4,5-dihydroisoxazole (5c):7g White
solid; 37.5 mg, 86% yield; 1H NMR (600 MHz, CDCl3) δ 7.68–7.66 (m,
2H), 7.46–7.41 (m, 3H), 5.10–5.05 (m, 1H), 3.64–3.60 (m, 1H), 3.32–
3.24 (m, 2H), 3.17 (dd, J = 13.8, 6.6 Hz, 1H). 13C NMR (150 MHz,
CDCl3) δ 156.4, 130.6, 128.8, 128.6, 126.8, 111.5, 78.7, 39.4, 37.0.
HRMS (ESI) ([M+H]+) Calcd. For [C11H11N2OS]+: 219.0587, Found:
219.0586.
O
O
O
N
S
O
Ph
O
Br
N
(3-Phenyl-4,5-dihydroisoxazol-5-yl)methyl
naphthalene-2-
1
sulfonate (4f): White solid; 55.0 mg, 75% yield; H NMR (400 MHz,
CDCl3) δ 8.48 (s, 1H), 7.99–7.91 (m, 3H), 7.86–7.84 (m, 1H), 7.70–
7.61 (m, 2H), 7.58–7.56 (m, 2H), 7.42–7.34 (m, 3H), 4.98–4.91 (m,
1H), 4.25–4.14 (m, 2H), 3.43 (dd, J = 16.8, 10.8 Hz, 1H), 3.24 (dd, J =
17.2, 6.8 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 156.2, 135.4, 132.2,
131.9, 130.4, 129.9, 129.8, 129.5, 129.3, 128.7, 128.0, 127.9, 126.7,
122.4, 77.4, 69.5, 37.2. HRMS (ESI) ([M+H]+) Calcd. For
[C20H18NO4S]+: 368.0951, Found: 368.0952.
Ph
5-(Bromomethyl)-3-phenyl-4,5-dihydroisoxazole (5d):16 White
solid; 38.4 mg, 80% yield; 1H NMR (600 MHz, CDCl3) δ 7.69–7.65 (m,
2H), 7.44–7.39 (m, 3H), 5.02–4.97 (m, 1H), 3.57 (dd, J = 10.8, 4.2 Hz,
1H), 3.51 (dd, J = 16.8, 10.2 Hz, 1H), 3.41 (dd, J = 10.2, 8.4 Hz, 1H),
3.32 (dd, J = 17.4, 6.6 Hz, 1H). 13C NMR (150 MHz, CDCl3) δ 156.0,
130.3, 129.0, 128.7, 126.7, 79.6, 39.5, 33.1. HRMS (ESI) ([M+H]+)
Calcd. For [C10H11BrNO]+: 240.0019, Found: 240.0018.
O
Me
O
O
N
S
O
I
O
N
Ph
Ph
(3-Phenyl-4,5-dihydroisoxazol-5-yl)methyl methanesulfonate (4g):
White solid; 33.7 mg, 66% yield; H NMR (600 MHz, CDCl3) δ 7.67–
5-(Iodomethyl)-3-phenyl-4,5-dihydroisoxazole (5e):17 White solid;
54.5 mg, 95% yield; H NMR (600 MHz, CDCl3) δ 7.69–7.65 (m, 2H),
7.44–7.39 (m, 3H), 4.95–4.90 (m, 1H), 3.52 (dd, J = 17.4, 10.8 Hz,
1H), 3.42 (dd, J = 10.2, 4.2 Hz, 1H), 3.25–3.21 (m, 2H). 13C NMR (150
MHz, CDCl3) δ 155.8, 130.3, 129.0, 128.7, 126.7, 80.4, 41.0, 7.5.
HRMS (ESI) ([M+H]+) Calcd. For [C10H11INO]+: 287.9880, Found:
287.9879.
1
1
7.65 (m, 2H), 7.45–7.39 (m, 3H), 5.03–4.98 (m, 1H), 4.40–4.32 (m,
2H), 3.49 (dd, J = 16.8, 10.8 Hz, 1H), 3.28 (dd, J = 17.4, 7.2 Hz, 1H),
3.07 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 156.5, 130.4, 128.8, 128.7,
126.7, 77.7, 69.4, 37.6, 36.8. HRMS (ESI) ([M+H]+) Calcd. For
[C11H14NO4S]+: 256.0638, Found: 256.0638.
O
OPh
N
Ph
8 | Organic & Biomolecular Chemistry, 2019, 00, 1-3
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ARTICLE
O
2
For selected examples on HIRs, see: (a) E. MejíaVaienwdArAtic.leToOgnlninie,
ACS Catal., 2012, 2, 521; (b) C. ZhanDgO, IS:.10L.i1u0,39B/.CS9uOnB0a2n42d4GJ.
Tian, Org. Lett., 2015, 17, 4106; (c) G. Wang, C. Chen and J.
Peng, Chem. Commun., 2016, 52, 10277; (d) G. Li, C. A.
Morales-Rivera, F. Gao, Y. Wang, G. He, P. Liu and G. Chen,
Chem. Sci., 2017, 8, 7180; (e) W. Guo, H. Gong, Y. Zhang, L.
Wen and M. Li, Org. Lett., 2018, 20, 6394; (f) A. Yoshimura,
M. T. Shea, O. Guselnikova, P. S. Postnikov, G. T. Rohde, A.
Saito, M. S. Yusubov,V. N. Nemykin and V. V. Zhdankin,
Chem. Commun., 2018, 54, 10363; (g) M. Reitti, R.
Gurubrahamam, M. Walther, E. Lindstedt and B. Olofsson,
Org. Lett., 2018, 20, 1785; (h) B. Mai, K. J. Szabó and F. Himo,
ACS Catal., 2018, 8, 4483; (i) K. Farshadfar, A. Chipman, B. F.
Yates and A. Ariafard, ACS Catal., 2019, 9, 6510; (j) G.-X. Li, X.
Hu, G. He and Gong Chen, Chem. Sci., 2019, 10, 688.
N3
N
Ph
5-(Azidomethyl)-3-phenyl-4,5-dihydroisoxazole (5f):7d White solid;
36.0 mg, 89% yield; H NMR (600 MHz, CDCl3) δ 7.68–7.67 (m, 2H),
7.42–7.41 (m, 3H), 4.94–4.90 (m, 1H), 3.54–3.43 (m, 3H), 3.22 (dd, J
= 16.8, 6.6 Hz, 1H). 13C NMR (150 MHz, CDCl3) δ 156.4, 130.3, 129.1,
128.7, 126.7, 79.1, 53.5, 37.8. HRMS (ESI) ([M+H]+) Calcd. For
[C10H11N4O]+: 203.0927, Found: 203.0928.
1
O
O
N
N
3
(a) D. Wang, X. Hao, D. Wu and J. Yu, Org. Lett., 2006, 8,
3387; (b) A. Shrestha, M. Lee, A. L. Dunn and M. S. Sanford,
Org. Lett., 2018, 20, 204; (c) X. Wang, Y. Ye, S. Zhang, J. Feng,
Y. Xu, Y. Zhang and J. Wang, J. Am. Chem. Soc., 2011, 133,
16410; (d) D. Hari and J. Waser, J. Am. Chem. Soc., 2016,
138, 2190; (e) A. Sharma and J. F. Hartwig, Nature, 2015,
517, 600; (f) S. Bertho, R. Rey-Rodriguez, C. Colas, P.
Retailleau and I. Gillaizeau, Chem. Eur. J., 2017, 23, 17674;
(g) Z. Wang, M. Kanai and Y. Kuninobu, Org. Lett., 2017, 19,
2398; (h) L. Wang, H. Li and L. Wang, Org. Lett., 2018, 20,
1663; (i) Y. Wang, L. Zhang, Y. Yang, P. Zhang, Z. Du and C.
Wang, J. Am. Chem. Soc., 2013, 135, 18048; (j) A. Ariafard,
ACS Catal., 2014, 4, 2896; (k) X. Hu, X. Yang and T. Loh, ACS
Catal., 2016, 6, 5930; (l) S. V.-Céspedes, X. Wang and F.
Glorius, ACS Catal., 2018, 8, 242; (m) X.-Q. Hu, G. Feng, J. -
R. Chen, D. -M. Yan, Q. -Q. Zhao, Q. Wei and W.-J. Xiao, Org.
Biomol. Chem., 2015, 13, 3457; (n) C. Ye, X. Kou, G. Yang, J.
Shen and W. Zhang, Tetrahedron Lett., 2019, 60, 1148.
For recent examples with respect to Fe-catalysis, see: (a) C.
Wang, C. Wu and S. Ge, ACS Catal., 2016, 6, 7585; (b) N. Zhu,
J. Zhao and H. Bao, Chem. Sci., 2017, 8, 2081; (c) W. Jian, L. Ge,
Y. Jiao, B. Qian and H. Bao, Angew. Chem. Int. Ed., 2017, 56,
3650; (d) L. Ilies, Y. Zhou, H. Yang, T. Matsubara, R. Shang
and E. Nakamura, ACS Catal., 2018, 8, 11478; (e) M. E.-Viguri,
S. E. Neale, N. T. Coles, S. A. Macgregor and R. L. Webster J.
Am. Chem. Soc., 2019, 141, 572; (f) M. Hu, J. Lian, W. Sun, T.
Qiao and S. Zhu, J. Am. Chem. Soc., 2019, 141, 4579; (g) C.
Kennedy, H. Zhong, R. MacCauley and P. J. Chirik, J. Am.
Chem. Soc., 2019, 141, 8557; (h) X. Jiang, J. Liu and S. Ma,
Org. Process Res. Dev., 2019, 23, 825; (i) X. Liu, B. Cheng, Y.
Guo, X. Chu, W. Rao, T. Loh and Z. Shen, Org. Chem. Front.,
2019, 6, 1581.
(a) J. Wityak, T. M. Sielecki, D. J. Pinto, G. Emmett, J. Y. Sze, J.
Liu, E. Tobin, S. Wang, B. Jiang, P. Ma, S. A. Mousa, R. R.
Wexler and R. E. Olson, J. Med. Chem., 1997, 40, 50; (b) S.
Castellano, D. Kuck, M. Viviano, J. Yoo, F. López-Vallejo, P.
Conti, L. Tamborini, A. Pinto, J. L. Medina-Franco and G. J.
Sbardella, J. Med. Chem., 2011, 54, 7663; (c) K. Kaur, V.
Kumar, A. K. Sharma and G. K. Gupta, Eur. J. Med. Chem.,
2014, 77, 121; (d) J. C. Jewett, E. M. Sletten and C. R.
Bertozzi, J. Am. Chem. Soc., 2010, 132, 3688; (e) P. K.
Poutiainen, J. J. Palvimo, A. E. Hinkkanen, A. Valkonen, T. K.
Väisänen, R. Laatikainen and J. T. Pulkkinen, J. Med. Chem.,
2013, 56, 1064; (f) K.-H., Hwang, J.-S. Lim, S.-H. Kim, M.-S.
Jeon, D.-G. Lee, K.-H. Chung, S.-J. Koo and J.-H. Kim, J. Agric.
Food Chem., 2013, 61, 9285; (g) M. A. Arai, M. Kuraishi, T.
Arai and H. Sasai, J. Am. Chem. Soc., 2001, 123, 2907; (h) A.
A. Fuller, B. Chen, A. R. Minter and A. K. Mapp, J. Am. Chem.
Soc., 2005, 127, 5376.
Ph
3-Phenyl-5-(((2,2,6,6-tetramethylpiperidin-1-yl)oxy)methyl)-4,5-
dihydroisoxazole (6):7a White solid; 58.2 mg, 92% yield; 1H NMR
(600 MHz, CDCl3) δ 7.62–7.59 (m, 2H), 7.32–7.31 (m, 3H), 4.81–4.76
(m, 1H), 3.92–3.87 (m, 2H), 3.29 (dd, J = 16.2, 10.8 Hz, 1H), 3.17 (dd,
J = 16.2, 7.2 Hz, 1H), 1.46-1.35 (m, 5H), 1.23–1.21 (m, 1H), 1.11 (s,
6H), 0.99 (d, J = 4.2 Hz, 6H). 13C NMR (150 MHz, CDCl3) δ 156.06,
129.8, 129.7, 128.6, 126.6, 79.1, 77.5, 60.0, 59.9, HRMS (ESI)
([M+H]+) Calcd. For [C19H29N2O2]+: 317.2224, Found: 317.2227.
O
OH
N
Ph
(3-Phenyl-4,5-dihydroisoxazol-5-yl)methanol (3a-OH):18 1H NMR
(600 MHz, CDCl3) δ 7.67–7.65 (m, 2H), 7.42–7.38 (m, 3H), 4.89–4.84
(m, 1H), 3.87 (dd, J = 12.6, 3.6 Hz, 1H), 3.69 (dd, J = 12.0, 4.8 Hz,
1H), 3.33 (m, 2H), 2.23 (s, 1H). 13C NMR (150 MHz, CDCl3) δ 157.06,
130.16, 129.29, 128.68, 126.69, 81.22, 63.65, 36.30.
4
Acknowledgements
This work is financially supported by the National Science
Foundation of China (21772062, 21572078, 21772061), the
Natural Science Foundation of Anhui Province (1708085QB28).
5
Notes and references
1
For recent reviews on HIRs, see: (a) V. V. Zhdankin and P. J.
Stang, Chem. Rev., 2008, 108, 5299; (b) J. Charpentier, N.
Früh and A. Togni, Chem. Rev., 2015, 115, 650; (c) A.
Yoshimura and V. V. Zhdankin, Chem. Rev., 2016, 116, 3328;
For elegant works on HIRs, see: (d) B. H. Rotstein, N. A.
Stephenson, N. Vasdev and S.-H. Liang, Nat. Comm., 2014,
Article number: 4365; (e) R. Frei, M. D. Wodrich, D. Hari, P.
Borin, C. Chauvier and J. Waser, J. Am. Chem. Soc., 2014,
136, 16563; (f) L. Ling, K. Liu, X. Li and Y. Li, ACS Catal., 2015,
5, 2458; (g) J, Zhang, K, J. Szabo and F. Himo, ACS Catal.,
2017, 7, 1093; (h) S. Wang, Q. Gu and S. You, J. Org. Chem.
2017, 82, 11829; (i) A. Maity, S. Hyun and D. C. Powers, Nat.
Chem., 2018, 10, 200; (j) B. Yang, D. Yu, X. Xu and F. Qing,
ACS Catal., 2018, 8, 2839; (k) B. Xu, Y. Gao, J. Han, Z. Xing, S.
Zhao, Z. Zhang, R. Ren and L. Wang, J. Org. Chem., 2019, 84,
10136; (l) J. Zhao, Z. Liu, S. Wu and Y. Chen, Org. Lett., 2019,
21, 2077.
6
For selected examples using transition metal catalysis, see:
(a) C. Li, H. Deng, C. Li, X. Jia and J. Li, Org. Lett., 2015, 17.
5718; (b) F. Chen, F. Zhu, M. Zhang, R. Liu, W. Yu and B. Han,
Org. Lett., 2017, 19, 3255; (c) R. Chen, Y. Zhao, S. Fang, W.
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Long, H. Sun and X. Wan, Org. Lett., 2017, 19, 5896; (d) Y. Li,
Organic & Biomolecular Chemistry
View Article Online
M. Gao, B. Liu and B. Xu, Org. Chem. Front., 2017, 4, 445; (e)
R. Chew and M. Wills, J. Org. Chem., 2018, 83, 2980; For
some metal-free systems, see: (f) H. Huang, F. Li, Z. Xu, J. Cai,
X. Ji and G. Deng, Adv. Synth. Catal., 2017, 359, 3102; (g) G.
Jang, J. Lee, J. Seo and S. Woo, Org. Lett., 2017, 19, 6448; (h)
E. Nagy and S. D. Lepore, Org. Lett., 2017, 19, 3695; (i) B. Mir,
S. Singh, R. Kumar and B. K. Patel, Adv. Synth. Catal., 2018,
360, 3801; (j) G. Zhao, L. Liang, C. Wen and R. Tong, Org.
Lett., 2019, 21, 315.
(a) B. Han, X. Yang, R. Fang, W. Yu, C. Wang, X. Duan and S.
Liu, Angew. Chem. Int. Ed., 2012, 51, 8816; (b) J. M. Neely
and T. Rovis, J. Am. Chem. Soc., 2013, 135, 66; (c) J. M. Neely
and T. Rovis, J. Am. Chem. Soc., 2014, 136, 2735; (d) L. Zhu,
H. Yu, Z. Xu, X. Jiang, L. Lin and R. Wang, Org. Lett., 2014, 16,
1562; (e) F. R.-Michailidis, K. F. Sedillo, J. M. Neely and T.
Rovis, J. Am. Chem. Soc., 2015, 137, 8892; (f) Q. Wei, J. Chen,
X. Hu, X. Yang, B. Lu and W. Xiao, Org. Lett., 2015, 17, 4464;
(g) X. Zhang, Z. Xiao, Y. Zhuang, M. Wang and Y. Kang, Adv.
Synth. Catal., 2016, 358, 1942; (h) W. Zhang, Y. Su, K. Wang,
L. Wu, B. Chang, Y. Shi and D. Huang, Org. Lett., 2017, 19,
376; (i) F. Meng, H. Zhang, K. Guo, J. Dong, A. Lu and Y. Zhu,
J. Org. Chem., 2017, 82, 10742; (j) L. Wang, M. Chen, L. Qi, Z.
Xu and W. Li, Chem. Commun., 2017, 53, 2056; (k) W. Han, Y.
Wang, J. Zhang, F. Chen, B. Zhou and B. Han, Org. Lett., 2018,
20, 2960.
DOI: 10.1039/C9OB02424G
7
8
9
(a) K. Dong, H. Qin, X. Bao, F. Liu and C. Zhu, Org. Lett., 2014,
16, 5266; (b) X. Yang, F. Chen, N. Zhou, W. Yu and B. Han,
Org. Lett. 2014, 16, 6476; (c) Z. Xu, L. Zheng, L. Li, L. Duan
and Y. Li, Org. Biomol. Chem., 2019, 17, 898.
(a) H. Tan, H. Li, W. Ji and L. Wang, Angew. Chem. Int. Ed.,
2015, 54, 8374; (b) D. Zha, H. Li, S. Li and L. Wang, Adv.
Synth. Catal. 2017, 359, 467.
10 The crystallographic data for compounds 3a (CCDC number:
1921843). These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
11 For the formation of 3a-OH via radical addition process
under visible light catalysis, see: W. Xiao, X. Hu, J. Chen, J.
Chen and D, Yan, Chem. Eur. J. 2016, 22, 14141. In this work,
a possible reaction mechanism not involving hydroxyl radical
was proposed and described in Scheme 4.
12 R. Rey-Rodriguez, P. Retailleau, P. Bonnet and I. Gillaizeau,
Chem. Eur. J., 2015, 21, 3572.
13 Radical scavenger TEMPO could trap the generated radical
species C to give 6 in 92% isolated yields (see details in
Supporting Information).
14 B. Roy and R. De, Monatsh, Chem., 2010, 141, 763.
15 J. Yu and C. Cai, Org. Biomol. Chem., 2018, 16, 490.
16 K. Dong, H. Qin, F. Liu and C. Zhu, Eur. J. Org. Chem., 2015,
2015, 1419.
17 X. Zhang, Z. Xiao, M. Wang, Y. Zhuang and Y. Kang, Org.
Biomol. Chem., 2016, 14, 7275.
18 D. Yamamoto, T. Oguro, Y. Tashiro, M. Soga, K. Miyashita, Y.
Aso and K. Makino, Eur. J. Org. Chem., 2016, 2016, 5216.
10 | Organic & Biomolecular Chemistry, 2019, 00, 1-3
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DOI: 10.1039/C9OB02424G
Room temperature iron(II)-catalyzed radical cyclization of
unsaturated oximes with hypervalent iodine reagents
Shichao Yang a Hongji Li,*,a Pinhua Li,a Jingya Yang a and Lei Wang*,a,b
Abstract ： An iron (II)-catalyzed radical cyclization of oximes with
hypervalent iodine reagents was developed, which enabled the
construction of isoxazoline backbone.
OH
O
O
N
Nu
N
OH
I
O
O
-
O
O
Nu
80 ºC, 6-10 h
Nu = N3, OPh, SPh, SCN, Br, I
Diverse transformation
N
S
R
Fe(acac)2 (5 mol%)
DCM, rt, air, 6 h
S
R
Ar
Ar
O
Ph
O
Ar
30 examples, 49-90% yields
Iron catalysis
Hypervalent iodine reagents (HIRs)
Room temperature radical cyclization
Excellent group tolerance
a
Department of Chemistry, Huaibei Normal University, Huaibei,
Anhui 235000, P R China; E-mail: leiwang@chnu.edu.cn
Tel.: +86-561-380-2069; Fax: +86-561-309-0518
b State Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai 200032, P R China
This journal is © The Royal Society of Chemistry
[journal], [year], [vol], 00–00
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