Microwave-assisted copper-catalyzed stereoselective ring expansion of three-membered heterocycles with α-diazo-β-dicarbonyl compounds

Article abstract of DOI:10.1016/j.tet.2018.01.014

Microwave-assisted copper-catalyzed ring expansions of three-membered heterocycles with α-diazo-β-dicarbonyl compounds were investigated. Thiiranes generated 3-acyl-5,6-dihydro-1,4-oxathiines in the presence of copper sulfate and trans-3-acyl-5,6-dihydro-1,4-oxathiines as stereospecific products for 1,2-disubstituted cis-thiiranes through an intramolecular S_N2 process. Oxiranes gave rise to 2-acyl-5,6-dihydro-1,4-dioxines under the catalysis of copper hexafluoroacetylacetonate and cis-3-acyl-5,6-dihydro-1,4-dioxines as stereospecific products for 1,2-disubstituted cis-oxiranes via an intimate ion-pair mechanism. The current method provides a direct and simple strategy in efficient preparation of 3-acyl-5,6-dihydro-1,4-oxathiines and 2-acyl-5,6-dihydro-1,4-dioxines, important agents in medicinal and agricultural chemistry, from readily available thiiranes and oxiranes, respectively.

Full text of DOI:10.1016/j.tet.2018.01.014

Accepted Manuscript
Microwave-assisted copper-catalyzed stereoselective ring expansion of three-
membered heterocycles with α-diazo-β-dicarbonyl compounds
Siqi Li, Xingpeng Chen, Jiaxi Xu
PII:
S0040-4020(18)30036-X
10.1016/j.tet.2018.01.014
TET 29229
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 8 November 2017
Revised Date: 23 December 2017
Accepted Date: 9 January 2018
Please cite this article as: Li S, Chen X, Xu J, Microwave-assisted copper-catalyzed stereoselective ring
expansion of three-membered heterocycles with α-diazo-β-dicarbonyl compounds, Tetrahedron (2018),
doi: 10.1016/j.tet.2018.01.014.
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Siqi Li, Xingpeng Chen, and Jiaxi Xu
1

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Tetrahedron
journal homepage: www.elsevier.com
Microwave-assisted copper-catalyzed stereoselective ring expansion of three-
membered heterocycles with α-diazo-β-dicarbonyl compounds
Siqi Li, Xingpeng Chen, and Jiaxi Xu
State Key Laboratory of Chemical Resource Engineering, Department of Organic Chemistry, Faculty of Science, Beijing University of Chemical Technology,
Beijing 100029, People’s Republic of China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Microwave-assisted copper-catalyzed ring expansions of three-membered heterocycles with α-
diazo-β-dicarbonyl compounds were investigated. Thiiranes generated 3-acyl-5,6-dihydro-1,4-
oxathiines in the presence of copper sulfate and trans-3-acyl-5,6-dihydro-1,4-oxathiines as
stereospecific products for 1,2-disubstituted cis-thiiranes through an intramolecular SN2
process. Oxiranes gave rise to 2-acyl-5,6-dihydro-1,4-dioxines under the catalysis of copper
hexafluoroacetylacetonate and cis-3-acyl-5,6-dihydro-1,4-dioxines as stereospecific products
for 1,2-disubstituted cis-oxiranes via an intimate ion-pair mechanism. The current method
provides a direct and simple strategy in efficient preparation of 3-acyl-5,6-dihydro-1,4-
oxathiines and 2-acyl-5,6-dihydro-1,4-dioxines, important agents in medicinal and agricultural
chemistry, from readily available thiiranes and oxiranes, respectively.
Available online
Keywords:
Diazo compound
Oxarine
Thiirane
1,4-Dioxine
1,4-Oxathiine
Ring expansion
Copper catalyst
2017 Elsevier Ltd. All rights reserved
.
1. Introduction
3-Acyl-5,6-dihydro-1,4-oxathiines have been synthesized
mainly through the displacement of ethyl 2-chloro-3-
oxobutanoate with 2-mercaptoethanol and subsequent
cyclization.6 This is a general method for the preparation of
Vitavax. Alternative method is the cyclization of (E/Z)-2-
5,6-Dihydro-1,4-oxathiines and 1,4-dioxines are important
and indispensable structural units in medicinal and agricultural
chemistry.1-3 5,6-Dihydro-1,4-oxathiine-3-carboxanilides are
commercial fungicides and active anti-HIV agents.1-3 N-Aryl-
3-methyl-5,6-dihydro-1,4-dioxine-2-carboxamides are the
oxygen analogues of effective fungicide 5,6-dihydro-2-
methyl-N-phenyl-1,4-oxathiine-3-carboxamide (Vitavax) and
have the fungicidal activity against bean rust, a major disease
of cereal crops.4 Meanwhile, 2-[(4-methylphenyl)amino]-2-
oxoethyl 5,6-dihydro-1,4-dioxine-2-carboxylate is a potential
cruzain inhibitor to treat American trypanosomiasis.5 Thus,
such compounds are a kind of valuable fungicide candidates.
chloro-2-(2-hydroxyethylthio)butenamides
under
the
treatment of LiHMDS to afford 3-acyl-5,6-dihydro-1,4-
oxathiines in low yields.7 Hetero-Diels-Alder cycloadditions
of 2,4-dioxopentane-3-thione and electron-rich enolic ethers
have also been applied in the synthesis of 3-acyl-5,6-dihydro-
1,4-oxathiines.8
Previously reported synthesis of 5,6-dihydro-1,4-dioxine-2-
carboxylic acid derivatives generally required multi-step
reactions or under harsh conditions. For example, Dekeyser and
his coworkers prepared 5,6-dihydro-1,4-dioxine-2-carboxylic
acid derivatives from glycol and 3-chloroprop-1-yne through five
steps in 1998.4 Two years later, Hahn and his coworkers
developed a method for their synthesis from 3-ethoxy-1,1,1-
trifluoropropan-2-one via six steps.9 Moreover, Blanchot and his
coworkers realized a two-step synthetic route, but they used BuLi
and organotin reagents in their reactions.10 The aforementioned
methods hardly realized highly efficient preparation of 5,6-
dihydro-1,4-dioxine-2-carboxylic acid derivatives in high yields.
Recently, Achard and his coworkers reported a direct preparation
of 5,6-dihydro-1,4-dioxine-2-carboxylic acid derivatives from
epoxides and diazo compounds under the catalysis of
[CpRu(CH3CN)3][BArF].11 But the Ru catalyst is expensive and
the diazo substrates are limited to diazoketoesters only. In our
Cl
O
O
S
O
S
N
N
H
H
O
O
O
anti-HIV agent
Vitavax
O
O
H
R
O
O
N
O
O
O
N
H
O
cruzain inhibitor
oxygen analogs of Vitavax
Figure 1. Biologically active molecules containing 1,4-oxathiines and
1,4-dioxines
———
Corresponding author. Tel.: +0-8610-6443-5565; fax: +0-8610-6443-5565; e-mail: jxxu@mail.buct.edu.cn
2

Table 1. Synthesis of 3-acyl-5,6-dihydro-1,4-oxathiines 3 from thiiranes 1
continuing interest in the synthesis of heterocycles through ring
expansion of small heterocycles,12 we realized inexpensive
copper-catalyzed synthesis of 3-acyl-5,6-dihydro-1,4-oxathiines
and 2-acyl-5,6-dihydro-1,4-dioxines from thiiranes and oxiranes,
respectively, with α-diazo-β-dicarbonyl compounds, including
both diazoketoesters and diazodiketones. 1,2-Disubstituted cis-
thiiranes and oxiranes show completely opposite stereoselectivity
in the ring expansions (Scheme 1). Herein, we present our results.
ACCEPTED MANUSCRIPT
and α-diazo-β-dicarbonyl compounds 2a
O
O
O
O
X
O
O
R1
R2
O
R4
S
S
S
S
Cu Salts, DCE
O
O
O
R3
R4
+
R2
X = S, O
R1
Microwave, 100-150 °C, 20 min
O
O
Ph
O
O
O
N2
X
(+)
(+)
(+)
(+)
R3
3a 55%b
3c 51%
3b 47%
3d 56%
X = S, trans-products
X = O, cis-products
O
O
O
O
S
S
S
S
O
Scheme 1. Synthesis of 5,6-dihydro-1,4-oxathiines and 1,4-dioxines through
the ring expansion of thiiranes and oxiranes with α-diazo-β-dicarbonyl
compounds.
O
Ph
O
O
O
O
(+)
(+)
(+)
3h 0%
3f trace
3e 43%
3g trace
O
O
O
O
S
2. Results and Discussion
S
S
S
O
O
O
O
O
O
(
)
3
O
Ph
(
)
3
O
CF3
( )
3
O
O
2.1. Synthesis of 3-acyl-5,6-dihydro-1,4-oxathiines through
the ring expansion of thiiranes and α-diazo-β-dicarbonyl
compounds
3l 33%
3j 50%
3k 42%
3i 0%
O
O
O
O
S
S
S
S
Initially, 7-thiabicyclo[4.1.0]heptane (1a) and ethyl 2-
diazo-3-oxobutanoate (2a) were employed as the model
substrates to optimize reaction conditions. Both Rh2(OAc)4,
Pd(OAc)2, Zn(OAc)2, Cu(hfacac)2·xH2O, Cu(CH3CN)4PF6,
(CF3SO3)2Cu, and CuSO4·5H2O salt catalysts and BF3·OEt,
FeCl3, and AlCl3 Lewis acid catalysts were attempted.
Different solvents 1,2-dichloroethane (DCE), toluene,
dioxane, and acetonitrile were screened. The optimum reaction
conditions were finally identified as follows: 1a:2a = 2:1 in the
presence of 2 equiv. of CuSO4·5H2O in DCE as solvent at 100 oC
for 20 min microwave irradiation.13
(
)
3
O
(
)
O
(
)
(
)
O
O
5
3
5
3n 35%
3o 42%
3p 40%
3m 38%
O
O
O
O
S
S
S
S
Ph
O
Ph
Ph
O
O
(
)
5
O
O
O
O
3s 27%
3q 26%
3r 30%
3t 24%
O
O
S
S
O
Ph
O
O
3u 0%
3v trace
a)
Reaction conditions: Diazo compounds 2 (0.3 mmol) and thiiranes 1 (0.6
Under the optimized reaction conditions, the reaction scope
was evaluated (Table 1). The reactions of 7-
thiabicyclo[4.1.0]heptane (cyclohexene sulfide) (1a) and
different α-diazo-β-dicarbonyl compounds 2 indicated that
diazoketoesters (alkyl 2-diazo-3-oxobutanoates and 2-diazo-3-
mmol) were added in DCE (1.0 mL) in a 10 mL microwave tube, then
CuSO4·5H2O (0.6 mmol) was added, and the reaction mixture was stirred at
100 °C for 20 mins under microwave irradiation in a sealed vessel. All yields
are isolated yields.
On the basis of the stereostructure of products 3a-e, we
proposed the following mechanism for reactions of thiiranes 1
and α-diazo-β-dicarbonyl compounds 2. The reaction of cyclic
thiirane 1a and diazo compound 2a is selected as an example to
present the mechanism (Scheme 2). Diazo compound 2a first
oxo-3-phenylpropanoate
)
and cyclic diazodiketones
(2-
diazocyclohexane-1,3-diones
)
generated the corresponding
desired products 3a-e in trans-configuration in moderate
yields. Their stereostructure was determined by the single
crystal X-ray diffraction analysis of the representative
compound 3c.13 However, linear diazodiketones (3-diazo-2,4-
pentanedione and 2-diazo-1-phenyl-1,3-butanedione), diethyl
2-diazomalonate, and electron-deficient ethyl 2-diazo-4,4,4-
trifluoro-3-oxobutanoate failed in the reaction. Products 3f,g
were obtained in trace amounts and products 3h,i were not
observed. Capozzi and coworkers previously synthesized cis-
1-(3-methyl-4a,7,8,8a-tetrahydro-6H-pyrano[2,3-
b][1,4]oxathiine-2-yl)ethan-1-one by the hetero-Diels-Alder
reaction of 2,4-dioxopentane-3-thione and dihydropyrane.8
Currently, we synthesized ethyl trans-3-acyl-4a,5,6,7,8,8a-
hexahydrobenzo[b][1,4]oxathiines. Both diazoketoesters and
cyclic diazodiketones were reacted with monosubstituted
thiiranes to afford the corresponding desired products 3j-t in
low to moderate yields. However, no reaction occurred for 6-
thiabicyclo[3.1.0]hexane (cyclopentene sulfide) and ethyl 2-
diazo-3-oxobutanoate. For 1,1-disubstituted 1-methyl-1-(2-
phenylethyl)thiirane, only a trace amount of product 3v was
obtained possibly due to the steric hindrance of 1,1-
disubstituted thiirane.
reacts with CuSO4·5H2O to generate
a
metal carbene
intermediate A by loss of nitrogen. Thiirane 1a nucleophilically
attacks the intermediate A and further forms a metal sulfonium
ylide intermediate B. Accompanied by the departure of the
copper complex, the original ketonic carbonyl isomerizes into an
enolate, which nucleophilically attacks the thiirane from the
backside of the C-S bond, leading to the cleavage of the C-S
bond to generate the ring expansion product 3a. During the ring-
opening reaction, the configuration of the attacked carbon is
inverted as the enolate anion attacks from the back of the three-
membered ring, resulting in the formation of trans-product 3a
from cis-thiirane 1a. For monosubstituted thiiranes, since the
thiirane ring in the intermediates B is partially positively charged,
the enolate anion is more nucleophilic to attack the carbon atom
with more substituents,14,15 and 6-substituted products 3j-3t are
generated.
3

and fast, having no opportunity to react with epoxide 4a. Thus,
ACCEPTED MANUSCRIPT
we attempted to use a syringe pump to inject 2a dropwise into a
solution of 4a and a catalyst. Gratifyingly, we isolated the desired
product ethyl 3-methyl-5-phenylmethyl-5,6-dihydro-1,4-dioxine-
2-carboxylate (5a) in a low yield. After a series of optimizations,
we still did not get a satisfied yield (detailed results not shown
here), so we tried to use microwave to assist our reaction because
microwave can selectively heat polar reactants.18
With the assistance of microwave irradiation, we screened
various inexpensive copper catalysts, such as Cu(acac)2,
Cu(hfacac)2·xH2O, CuSO₄·5H₂O, and Cu(OTf)2 (Table 2, entries
1−10). Cu(hfacac)2·xH2O was discovered as the best catalyst
(Table 2, entry 7). The encouraging results prompted us to
optimize the reaction conditions further. The yield also varied
with temperature, reaction time, and solvents. The yield was
improved when the reaction temperature was raised from 100 oC
to 150 oC (Table 2, entries 2, 4, 6, and 7). Shortening the reaction
time from 60 min to 40 min, 30 min, or 20 min had a positive
influence on the yield of 3a (Table 2, entries 7, 11, 12 and 13).
However, further shortening time to 15 min to 10 min caused
decrease of the yield due to unfinished reaction with lots of
reagents remained (Table 2, entries 14 and 15). But the yield
decreased for the 20 min. reaction when the temperature was
further increased to 160 oC (Table 2, entry 16). For solvent
optimization, 1,2-dichloroethane (DCE), toluene, and
dichloromethane (DCM) were screened (Table 2, entries 7, 8, and
17). Toluene caused a mussy system after reaction and
dichloromethane could not reach the best reaction temperature
due to its low boiling point. Adjusting the equivalent of oxirane
4a and diazo compound 2a did not produce a good effect to the
yield of 5a (Table 2, entries 18 and 19). Finally, after all these
optimizations, we selected to use 1.5 equiv. of 2-diazo-3-
oxobutanoate (2a) to react with one equivalent of 2-
benzyloxirane (4a) under the catalysis of 10 mol%
Cu(hfacac)2·xH2O at 150 oC in DCE with the assistance of
microwave irradiation for 20 min. (Table 2, entry 13).
Scheme 2. Mechanistic rationale on the stereospecific ring expansion
of 7-thiabicyclo[4.1.0]heptane (1a) and different α-diazo-β-
dicarbonyl compounds 2 in the presence of copper sulfate
pentahydrate.
2.2. Synthesis of 2-acyl-5,6-dihydro-1,4-dioxines through the
ring expansion of oxiranes and α-diazo-β-dicarbonyl
compounds
After success in the synthesis of 3-acyl-5,6-dihydro-1,4-
oxathiines
3 from thiiranes 1 with α-diazo-β-dicarbonyl
compounds 2 through the ring expansion reactions,13 we turned
our attention to the synthesis of 2-acyl-5,6-dihydro-1,4-dioxines
from oxiranes and α-diazo-β-dicarbonyl compounds. We first
chose the reaction of 2-benzyloxirane (4a) and ethyl 2-diazo-3-
oxobutanoate (2a) as a model reaction to optimize the reaction
conditions. Because many reactions between small heterocyclic
rings and diazo compounds share the feature of excessive diazo
compounds,16,17 we decided to use 1.5 equiv of diazo compound
2a. We started our optimization by simply mixing the two
reactants and a metal catalyst together at room temperature, but
after 3 h, no reaction occurred. Then we mixed both the reagents
and different metal catalysts together in various refluxing
solvents, but we did not get any new products. After all these
attempts, we found that diazo compound 2a decomposed easily
Table 2. Optimization for the reaction of 2-benzyloxirane (4a) and ethyl 2-diazo-3-oxobutanoate (2a) under microwave irradiation a
O
O
Cat., Solvent
O
O
Ph
+
Ph
OEt
Microwave
O
CO2Et
4a
N2
5a
2a
Entry
1
Catalyst (10 mol%)
Cu(acac)2
Time/Min
Solvent
Temperature/oC
Yield/%b
60
60
60
60
60
60
60
60
60
60
40
30
DCE
DCE
DCE
DCE
DCE
DCE
DCE
100
100
120
120
135
130
150
150
150
150
150
150
10
8
2
Cu(hfacac)2·xH2O
Cu(acac)2
3
8
4
Cu(hfacac)2·xH2O
Cu(acac)2
20
11
21
26
8
5
6
Cu(hfacac)2·xH2O
Cu(hfacac)2·xH2O
Cu(hfacac)2·xH2O
CuSO₄·5H₂O
7
8
Toluene
DCE
9
8
10
11
12
Cu(OTf)2
DCE
13
24
32
Cu(hfacac)2·xH2O
Cu(hfacac)2·xH2O
DCE
DCE
4

13
14
Cu(hfacac)2·xH2O
Cu(hfacac)2·xH2O
Cu(hfacac)2·xH2O
Cu(hfacac)2·xH2O
Cu(hfacac)2·xH2O
Cu(hfacac)2·xH2O
Cu(hfacac)2·xH2O
20
DCE
150
150
150
160
70
49 (45 d)
31
ACCEPTED MANUSCRIPT
15
10
20
20
40
20
DCE
DCE
DCE
DCM
DCE
DCE
15
28
16
27
17
10
18C
19C
150
150
35
23
b
1
aWithout special notes, reaction conditions: diazo compound 2a (1.5 equiv). The yield is determined by H NMR with 4-iodonitrobenzene as an internal
standard. c3 equiv of 2a. d Isolated yield.
With the optimal conditions for the preparation of ethyl 5-
benzyl-3-methyl-5,6-dihydro-1,4-dioxine-2-carboxylate (3a), we
evaluated the scopes of oxiranes 4 and diazo compounds 2. The
results are present in Table 3. The reactivity between varies of
oxiranes 4 and diazo compounds 2 suggested that both 2-alkyl
and 2-aryloxiranes 4 can react with diazoketoesters (2a, d, g),
except for ones with strong electron-withdrawing groups (2e),
and linear diazodiketones (2b,f), affording the corresponding 5,6-
dihydro-1,4-dioxine-2-carboxylates 5a, d, f, g, i, k, n and 5,6-
dihydro-1,4-dioxin-2-yl ketones 5b, e, j, m, respectively.
Comparison with the reactions of different oxiranes 4 with ethyl
2-diazo-3-oxobutanoate (2a) and 3-diazopentane-2,4-dione (2b)
indicated that the more electron-withdrawing the diazo
compounds are, the lower yields obtained (Table 3, entries 1, 2, 4,
5, 9, and 10). The reaction of 2-phenyloxirane (4c) and ethyl 2-
diazo-4,4,4-trifluoro-3-oxobutanoate (2e) further supports this
conclusion
(Table
3,
entry
8).
However,
2-
(phenoxymethyl)oxirane (1f) did not produce the corresponding
product 5l (Table 3, entry 12). We supposed that it was because
there were two different oxygen atoms in oxirane 1f so that there
might exist a competitive coordination with copper in the catalyst
between them, resulting in no desired product 5l generated in the
reaction. Furthermore, a cyclic diazodiketone compound 2-
diazocyclohexane-1,3-dione (2c) was attempted, but it failed to
undergo the reaction (Table 3, entry 3).
Table 3. Synthesis of 2-acyl-5,6-dihydro-1,4-dioxines 5 from oxiranes 4 and α-diazo-β-dicarbonyl compounds 2
Isolated
yield/%
Entry
1
Oxirane
4
Diazo compound
2
Product
5
4a
2a
5a
45
2
3
4a
4a
2b
2c
5b
5c
31
-
NR
4
5
4b
4b
2a
2b
5d
5e
42
24
O
O
O
N2
5

ACCEPTED MANUSCRIPT
6
4c
2a
5f
40
7
8
4c
4c
2d
5g
5h
18
2e
2a
-
NR
9
4d
4d
5i
5j
27
20
10
2b
11
12
4e
4f
2a
2d
5k
5l
27
-
NR
13
14
4g
4h
2f
5m
5n
10
33
±
±
2g
To identify the regioselectivity and structures of products
5a,b,d-g,i-k in the reactions, we performed 2D HMBC NMR
spectrum of the representative product 5i, of which the structure
is 5iA or 5iB (Figure 2). The spectrum showed that a weak
interaction between the CH33group (2.26 ppm) and the benzylic
carbon (75.05 ppm) and a J coupling between the methylene
group (4.20 ppm) in 1,4-dioxine and C(sp2) attached to the
carboxylate group, indicating that product 5i should possess the
structure of 5iA. The results suggest that products 5 were
generated through the enolate attacking on the more substituted
carbon atom of oxiranes 4 because the oxirane ring possesses
positive charge, similar to protonated or Lewis acid-coordinated
oxiranes, after the oxygen in the oxirane ring nucleophilically
attacks the metallocarbenes generated from diazo compounds 2
and copper catalyst (vide post Scheme 3).
Figure 2. Two possible structures of product 5i.
For
1
,2-disubstituted
cis-oxiranes,
7-
oxabicyclo[4.1.0]heptane (cyclohexene oxide) (4g) afforded the
corresponding cis-product 5m, of which cis-configuration was
determined from the coupling constant (J = 2.9 Hz) of the
protons on the carbon atoms next to the oxygen atoms (positions
4a and 8a in 5m) by comparison with previously reported data
(Table 3, entry 13).11,19 To further verify the stereosturcture of
product 5m, the reaction of 9-oxabicyclo[6.1.0]nonane
(cyclooctene oxide) (4h) and ethyl 2-diazo-3-oxo-3-
phenylpropanoate (2g) was performed under the catalysis of
Cu(hfacac)2·xH2O, affording the desired product 5n (Table 3,
6

1
entry 14). Product 5n shows the identical H NMR data to the
When thiirane 1a was used as starting material under the
ACCEPTED MANUSCRIPT
.
o
previously reported cis-product 5n obtained in the same reaction
conditions for oxiranes (Cu(hfacac)2 xH2O, 150 C, DCE), the
thiirane 1a decomposed completely without observation of the
corresponding cis-oxathiine. Even the reaction was conducted at
100 oC. No desired product was observed as well, but some
thiirane 1a remained.
under the catalysis of [CpRu(CH3CN)3][BArF].11
The results in the ring expansion of 1,2-disubstituted cis-
oxiranes 4 are obviously different from those in the ring
expansion of thiiranes 1.13 For the reactions of thiiranes 1, the
ring expansion undergoes an intramolecularly bimolecular
Finally, we hoped to extend the strategy into the reactions of
aziridines and α-diazo-β-dicarbonyl compounds 2, attempting to
synthesize 3-acyl-5,6-dihydro-1,4-oxazines through similar ring
expansion reactions. However, after many attempts in different
solvents under the catalysis of various transition metal catalysts,
applied in the reactions of thiiranes and oxiranes, no desired
product was observed.
substitution (SN2), generating trans-products
3 from 1,2-
disubstituted cis-thiiranes 1. However, in the current reactions,
1,2-disubstituted cis-oxiranes 4 afforded the corresponding cis-
products 5. The results suggests that the reaction should undergo
an intimate ion-pair mechanism rather than the SN2 mechanism.
To explain the ring expansion reaction between oxiranes 4 and
diazo compounds 2, we proposed the mechanism shown in
Scheme 3. First of all, diazo compounds 2 coordinate with
.
Cu(hfacac)2 xH2O and discharge
a molecule of nitrogen,
3. Conclusion
generating metallocarbenes I. Then, oxiranes 4 attack the
electron-deficient metallocarbenes I to produce metal oxonium
ylide intermediates II. The intermediates II undergo the cleavage
of the more substituted C-O bond of the oxirane ring because the
substituents can stabilize the positive charged carbocations and
simultaneous release of the copper catalyst to form enolate
anions. That is, intimate ion-pairs III are generated and further
combine the enolates and carbocations to afford six-membered
ring products 5 through the intimate ion-pair process.
In conclusion, we successfully provided a convenient and
economic synthetic preparation of important 3-acyl-5,6-dihydro-
1,4-oxathiine and 2-acyl-5,6-dihydro-1,4-dioxine derivatives
from readily available thiiranes and oxiranes with α-diazo-β-
dicarbonyl compounds under the catalysis of commercial
available and inexpensive copper catalysts. The assistance of
microwave irradiation shortens the reaction time extremely to
only 20 min. In addition, the substrate scope expanded to not
only diazoketoesters, but also diazodiketones. The two ring
expansion
reactions
showed
completely
different
stereoselectivities for 1,2-disubstituted cis-three-membered
heterocycles because thiiranes underwent the bimolecular
nucleophilic substitution mechanism, while oxiranes took place
the intimate ion-pair process. However, aziridines produced
complex mixtures under similar conditions. Although the yields
are from low to moderate, the current methods provide a direct
and simple strategy in efficient preparation of 3-acyl-5,6-
dihydro-1,4-oxathiines and 2-acyl-5,6-dihydro-1,4-dioxines.
4. Experimental Section
4.1 General Information
Unless otherwise noted, all materials were purchased from
commercial suppliers. DCE was refluxed over CaH2 and freshly
distilled prior to use. Flash column chromatography was
performed using silica gel (normal phase, 200−300 mesh) from
Branch of Qingdao Haiyang Chemical. Petroleum ether (PE)
o
used for column chromatography is 60−90 C fraction, and the
Scheme 3. Mechanistic rationale on the stereospecific ring
expansion of oxiranes 5 and α-diazo-β-dicarbonyl compounds 2
removal of residue solvent was accomplished under rotovap.
Reactions were monitored by thin-layer chromatography (TLC)
on silica gel GF254 coated 0.2 mm plates from Institute of Yantai
Chemical Industry. The plates were visualized under UV light, as
well as other TLC stains (10% phosphomolybdic acid in ethanol;
1% potassium permanganate in water; 10 g of iodine absorbed on
under the catalysis of Cu(hfacac)2·xH2O
.
To further verify the intimate ion-pair process, we tested the
reaction of enantiopure substrate (R)-phenyloxirane [(R)-4c] and
ethyl 2-diazo-3-oxobutanoate (2a) and obtained the
corresponding product (R)-5f with 88% e.e., supporting the
intimate ion-pair mechanism (Scheme 4). On the basis of cis-
selectivity in the reaction of cyclohexene oxide (4g) and
cyclooctene oxide (4h) and the intimate ion-pair mechanism, the
optical product 3f can be assumed as the R configuration.
1
30 g of silica gel). H and 13C NMR spectra were recorded on a
Bruker 400 MHz spectrometer in CDCl3 or DMSO-d6 with TMS
as an internal standard, and the chemical shifts (δ) are reported in
parts per million (ppm). All coupling constants (J) in 1HNMR are
absolute values given in hertz (Hz) with peaks labeled as single
(s), broad singlet (brs), doublet (d), triplet (t), quartet (q), and
multiplet (m). The IR spectra (KBr pellets, v [cm−1]) were taken
on a Nicolet 5700 FTIR spectrometer. HRMS measurements
were carried out on an Agilent LC/MSD TOF mass spectrometer.
Melting points were obtained on a Yanaco MP-500 melting point
apparatus and are uncorrected. Specific rotation was determined
on an Anton Paar MCP200 polarimeter. All microwave reactions
were conducted in CEM Discover SP micromave system
equipped with an infrared temperature detector. The enantiomeric
Scheme 4. Ring expansion with enantiopure epoxide (R)-4c.
7

excess was determined by chiral HPLC analysis using an Agilent
4.2.5 Ethyl 3-methyl-5-phenyl-5,6-dihydro-1,4-dioxine-2-
carboxylate (5f)
Yellow oil. Yield, 40%. H NMR (400 MHz, CDCl3) δ 7.47–7.33 (m, 5H,
ACCEPTED MANUSCRIPT
1260 LC instrument with Daicel Chiralpak AD-H column with a
mixture of hexane and isopropanol (90:10, v/v) as eluent at a flow
rate of 1.0 mL/min. at 254 nm.
1
ArH), 5.03 (dd, J = 8.4, 2.4 Hz, 1H, CH), 4.38–4.26 (m, 3H, 1H in CH2 &
CH2), 3.79 (dd, J = 11.3, 8.4 Hz, 1H, CH2), 2.37 (s, 3H, CH3), 1.38 (t, J = 7.1
Hz, 3H, CH3). 13C NMR (101 MHz, CDCl3) δ 163.8, 147.7, 135.8, 128.8,
128.8, 126.3, 125.0, 76.0, 68.5, 60.6, 17.8, 14.4. IR (KBr) 1738 cm-1. HRMS
All analytic data of thiiranes 1 and 3-acyl-5,6-dihydro-1,4-
oxatiines
3
were reported previously in our previous
and diazo
communications. Analytic data of oxiranes
4
(ESI) m/z: calcd. for C14H17O4+ [M+H]+: 249.1127; found: 249.1120
.
compounds 2 are provided in electronic supporting information.
4.2 General procedure for the synthesis of 2-acyl-5,6-dihydro-
1,4-dioxines 5
4.2.6 Ethyl (R)-3-methyl-5-phenyl-5,6-dihydro-1,4-dioxine-2-
carboxylate ((R)-5f)
Yellow oil. Yield, 41%. [α]20 = -24.3 (c, 1.10, CH2Cl2). 88% ee (Daicel
In a 10 mL reaction tube, oxirane 4 (0.2 mmol), diazo compound 2
D
.
(0.3 mmol) and Cu(hfacac)2 xH2O (9.54 mg, 0.02 mmol) were
Chiralpak AD-H column with a mixture of hexane and isopropanol (90:10,
dissolved in 2 mL of dries DCE. The reaction mixture was stirred
and irridated in a microwave reactor at 150 oC for 20 min. After the
solution was concentrated under reduced pressure, the resulting
residue was purified by silica gel column chromatography with a
mixture of petroleum ether/EtOAc (15:1 to 50:1, v/v) as eluent to
give pure product 5.
1
v/v) as eluent at a flow rate of 1.0 mL/min. at 254 nm). H NMR (400 MHz,
CDCl3) δ 7.47–7.33 (m, 5H, ArH), 5.03 (dd, J = 8.4, 2.4 Hz, 1H, CH), 4.38–
4.26 (m, 3H, 1H in CH2 & CH2), 3.79 (dd, J = 11.3, 8.4 Hz, 1H, CH2), 2.37 (s,
3H, CH3), 1.38 (t, J = 7.1 Hz, 3H, CH3). 13C NMR (101 MHz, CDCl3) δ 163.8,
147.7, 135.8, 128.8, 128.8, 126.3, 125.0, 76.0, 68.5, 60.6, 17.8, 14.4. IR
(KBr) 1738 cm-1. HRMS (ESI) m/z: calcd. for C14H17O4+ [M+H]+: 249.1127;
found: 249.1122
.
4.2.1 Ethyl 5-benzyl-3-methyl-5,6-dihydro-1,4-dioxine-2-
carboxylate (5a)
Yellow oil. Yield, 45%. H NMR (400 MHz, CDCl3) δ 7.34–7.20 (m, 5H,
4.2.7 Methyl 3-methyl-5-phenyl-5,6-dihydro-1,4-dioxine-2-
carboxylate (5g)11
Yellow oil. Yield, 18%. H NMR (400 MHz, CDCl3) δ 7.35–7.24 (m, 5H,
1
ArH), 4.30–4.22 (m, 3H, CH2 & CH), 4.05 (dd, J = 11.0, 2.4 Hz, 1H in CH2),
3.71 (dd, J = 11.0, 6.3 Hz, 1H in CH2), 3.00 (dd, J = 14.0, 6.6 Hz, 1H in CH2),
2.84 (dd, J = 14.0, 6.9 Hz, 1H in CH2), 2.24 (s, 3H, CH3), 1.33 (t, J = 6.9 Hz,
3H, CH3). 13C NMR (101 MHz, CDCl3) δ 164.0, 147.0, 136.2, 129.3, 128.6,
126.8, 124.8, 74.7, 66.0, 60.5, 37.2, 17.8, 14.4. IR (KBr) 1711, 1635 cm-1.
1
ArH), 4.94 (d, J = 8.0 Hz, 1H, CH), 4.23 (d, J = 11.2 Hz, 1H in CH2), 3.75 (s,
3H, CH3), 3.70 (dd, J =11.2, 8.0 1H in CH2), 2.28 (s, 3H, CH3). 13C NMR
(101 MHz, CDCl3) δ 164.1, 148.0, 135.7, 128.8, 128.8, 126.3, 125.7, 76.0,
68.4, 51.7, 17.7
.
+
HRMS (ESI) m/z: calcd. for C15H18NaO4 [M+Na]+: 285.1103; found:
285.1102
.
4.2.8 Ethyl 5-(4-chlorophenyl)-3-methyl-5,6-dihydro-1,4-dioxine-
2-carboxylate (5i)
4.2.2 1-(5-Benzyl-3-methyl-5,6-dihydro-1,4-dioxin-2-yl)ethan-1-
one (5b)
Yellow oil. Yield, 30.4%. H NMR (400 MHz, CDCl3) δ 7.38–7.19 (m, 5H,
Yellow oil. Yield, 26.6%. 1H NMR (400 MHz, CDCl3) δ 7.31 (d, J = 8.0 Hz,
2H, ArH), 7.20 (d, J = 7.7 Hz, 2H, ArH), 4.91 (dd, J = 8.0, 1.6 Hz, 1H, CH),
4.29–4.14 (m, 3H, CH2 & CH2), 3.65 (dd, J = 11.2, 8.4 Hz, 1H in CH2), 2.26
(s, 3H, CH3), 1.28 (t, J = 7.1 Hz, 3H, CH3). 13C NMR (101 MHz, CDCl3) δ
163.7, 147.4, 134.7, 134.3, 129.0, 127.6, 125.1, 75.2, 68.3, 60.7, 17.8, 14.4.
1
ArH), 4.24 (dddd, J = 6.9, 6.7, 2.2, 2.2 Hz, 1H, CH), 4.02 (dd, J = 11.1, 2.3
Hz, 1H in CH2), 3.67 (dd, J = 11.1, 6.4 Hz, 1H in CH2), 3.02 (dd, J = 13.9,
6.3 Hz, 1H in CH2), 2.82 (dd, J = 13.9, 7.3 Hz, 1H in CH2), 2.22 (s, 3H, CH3),
2.21 (s, 3H, CH3). 13C NMR (101 MHz, CDCl3) δ 195.5, 145.6, 136.2, 132.5,
129.3, 128.6, 126.9, 74.8, 65.5, 37.3, 27.5, 17.7. IR (KBr) 1735 cm-1. HRMS
(ESI) m/z: calcd. for C14H17O3 [M+H]+: 233.1178; found: 233.1189
+
IR (KBr): 1736, cm-1. HRMS (ESI) m/z: calcd. for C14H16ClO4 [M+H]+:
283.0737; found: 283.0761
.
+
.
4.2.9 1-(5-(4-Chlorophenyl)-3-methyl-5,6-dihydro-1,4-dioxin-2-
yl)ethan-1-one (5j)
4.2.3 Ethyl 3-methyl-5-phenethyl-5,6-dihydro-1,4-dioxine-2-
carboxylate (5d)
Yellow oil. Yield, 42%. H NMR (400 MHz, CDCl3) δ 7.33–7.16 (m, 5H,
1
Yellow oil. Yield, 20%. H NMR (400 MHz, CDCl3) δ 7.38 (d, J = 7.2 Hz,
2H, ArH), 7.26 (d, J = 8.8 Hz, 2H, ArH), 4.97 (dd, J = 8.0, 1.6 Hz, 1H, CH),
4.24 (d, J = 11.2 Hz, 1H in CH2), 3.80–3.63 (dd, J = 12.1, 3.9 Hz, 1H in CH2),
2.30 (s, 3H, CH3), 2.24 (s, 3H, CH3). 13C NMR (101 MHz, CDCl3) δ 196.4,
195.5, 145.9, 132.6, 130.9, 129.0, 128.5, 127.6, 75.3, 67.9, 27.6, 17.6. IR
(KBr) 1724, 1690 cm-1. HRMS (ESI) m/z: calcd. for C13H14ClO3+ [M+H]+:
1
ArH), 4.30–4.21 (m, 2H, CH2), 4.08 (dd, J = 11.0, 2.3 Hz, 1H in CH2), 4.04–
3.97 (m, 1H, CH), 3.67 (dd, J = 11.0, 6.9 Hz, 1H in CH2), 2.88–2.69 (m, 1H
in CH2), 2.25 (s, 3H, CH3), 1.96 (dddd, J = 14.2, 8.6, 8.6, 5.8 Hz, 1H, in CH2),
1.82 (dddd, J = 14.0, 9.1, 7.3, 5.0 Hz, 1H in CH2), 1.33 (t, J = 7.1 Hz, 3H).
13C NMR (101 MHz, CDCl3) δ 163.9, 147.1, 140.8, 128.5, 128.4, 126.1,
124.6, 73.2, 66.8, 60.5, 32.2, 31.0, 17.8, 14.4. IR (KBr) 1731, 1682 cm-1.
253.0631; found: 253.0617
.
4.2.10 Ethyl 5-(4-bromophenyl)-3-methyl-5,6-dihydro-1,4-
dioxine-2-carboxylate (5k)
HRMS (ESI) m/z: calcd. for C16H21O4+ [M+H]+: 277.1440; found: 277.1434
.
1
Yellow oil. Yield, 27%. H NMR (400 MHz, CDCl3) δ 7.57–7.07 (m, 5H,
4.2.4 1-(3-Methyl-5-phenethyl-5,6-dihydro-1,4-dioxin-2-yl)ethan-
1-one (5e)
Yellow oil. Yield, 24%. H NMR (400 MHz, CDCl3) δ 7.31–7.03 (m, 5H,
ArH), 4.90 (dd, J = 8.2, 2.4 Hz, 1H, CH), 4.28–4.16 (m, 3H, 1H in CH2 &
CH2), 3.65 (dd, J = 11.2, 8.2 Hz, 1H in CH2), 2.26 (s, 3H, CH3), 1.28 (t, J =
7.1 Hz, 3H, CH3). 13C NMR (101 MHz, CDCl3) δ 163.7, 147.4, 134.9, 131.9,
127.9, 125.1, 122.8, 75.3, 68.2, 60.7, 17.8, 14.4. IR (KBr) 1735 cm-1. HRMS
1
ArH), 3.98 (dd, J = 10.9, 2.4 Hz, 1H in CH2), 3.92 (ddt, J = 8.7, 4.8, 2.3 Hz,
1H, CH), 3.58 (dd, J = 10.9, 6.8 Hz, 1H in CH2), 2.82–2.63 (m, 2H, CH2),
2.16 (s, 3H, CH3), 2.13 (s, 3H, CH3), 1.88 (dddd, J = 14.2, 8.6, 8.6, 5.7 Hz,
1H, CH), 1.74 (dddd, J = 13.9, 9.0, 7.4, 4.7 Hz, 1H, CH). 13C NMR (101
MHz, CDCl3) δ 195.6, 145.6, 140.9, 132.4, 128.5, 128.4, 126.2, 73.3, 66.4,
32.2, 31.0, 27.5, 17.8. IR (KBr) 1689, 1597 cm-1. HRMS (ESI) m/z: calcd. for
(ESI) m/z: calcd. for C14H16BrO4+ [M+H]+: 327.0232; found: 277.0228
.
4.2.11 rel(4aR,8aS)-(3-Methyl-4a,5,6,7,8,8a-
hexahydrobenzo[b][1,4]dioxin-2-yl)(phenyl)methanone (5m)
Yellow oil. Yield, 10%. 1H NMR (400 MHz, DMSO-d6) δ 7.78–7.69 (m, 2H,
ArH), 7.51–7.48 (m, 3H, ArH). 4.19 (ddd, J = 7.6, 2.9, 2.4 Hz, 1H, CH), 4.09
(ddd, J = 6.4, 3.0, 2.9 Hz, 1H, CH), 2.17 (s, 3H, CH3), 1.82–1.34 (m, 8H,
C15H19O3+ [M+H]+: 247.1334; found: 247.1325
.
8

4CH2). 13C NMR (101 MHz, DMSO-d6) δ 189.3, 144.3, 137.9, 131.2, 129.7,
128.3, 127.4, 72.4, 69.1, 26.7, 26.4, 20.9, 19.9, 16.8. IR (KBr) 1734, 1665
cm-1. HRMS (ESI) m/z: calcd. for C16H19O3+ [M+H]+: 259.1134; found:
259.1135.
2006, (2), 315. (f) Dong, J.; Xu, J. X. Org. Biomol. Chem. 2017, 15,
ACCEPTED MANUSCRIPT
836.
13. Chen, X. P.; Xu, J. X. Tetrahedron Lett. 2017, 58, 1651.
14. Xu, J. X. Synthesis of Four- to Seven-Membered Heterocycles by Ring
Expansion: Ring Expansions of Thiiranes and Thietanes. In D’hooghe,
M.; Ha, H. J. Eds. Synthesis of 4- to 7-membered Heterocycles by
Ring Expansion. Top. Heterocycl. Chem. 2016, 41, 311. Springer,
Switzerland.
4.2.12 Ethyl rel(4aR,10aS)-3-phenyl-4a,5,6,7,8,9,10,10a-
octahydrocycloocta[b][1,4]dioxine-2-carboxylate (5n)11
1
Yellow oil, yield 33%. H NMR (400 MHz, Acetone-d6) δ 7.34 (s, 5H), 4.42
(dt, J = 9.0 and 2.8 Hz, 1H), 4.21 (dt, J = 9.0 and 2.8 Hz, 1H), 3.93 (q, J = 7.1
Hz, 2H), 2.18 – 1.89 (m, 3H), 1.97 – 1.42 (m, 9H), 0.94 (t, J = 7.1 Hz, 3H).
13C NMR (101 MHz, Acetone) δ 163.6, 145.9, 135.8, 129.8, 129.1, 128.0,
15. (a) Zhou, C.; Xu, J. X. Prog. Chem. 2012, 24, 238. (b) Yu, H.; Cao, S.
L.; Zhang, L. L.; Liu G.; Xu, J. X. Synthesis 2009, 13, 2205. (c) Li, X.
Y. Xu, J. X. Tetrahedron 2011, 67, 1681. (d) Dong, J.; Xu, J. X. Org.
Biomol. Chem. 2017, 15, 836.
125.8, 76.4, 74.1, 60.2, 28.2, 28.0, 26.1, 25.6, 23.8, 23.1, 13.8
.
Acknowledgments
16. (a) Nair, D.; Pavashe. P.; Katiyar, S.; Namboothir, I. N. N.
Tetrahedron Lett. 2016, 57, 3146. (b) Cheng,Q. Q.; Yu Qian, Y.;
Zavalij, P. Y.; Doyle, M. P. Org. Lett. 2015, 17, 3568. (c) Daniel J.
Mack, D. J.; Batory, L. A.; Njardarson, J. T. Org. Lett. 2012, 14, 378.
The project was supported by the National Natural Science
Foundation of China (Nos. 21572017, 21772010, and 21372025).
Supplementary Material
17. Rix, R.; Ballesteros-Garrido, R.; Zeghida, W.; Besnard ,C.; Lacour, J.
Angew. Chem. Int. Ed. 2011, 50, 7308.
General procedures for preparation of oxiranes 1 and diao
compounds 2, analytical data of oxiranes 1 and diazo compounds
18. (a) Xu, J. X. Prog. Chem. 2007, 19, 700. (b) Li, X. H.; Xu, J. X.
Tetrahedron 2016, 72, 5515. (c) Li, X. H.; Xu, J. X. Curr. Microw.
Chem. 2017, 4, 158. (d) Li, X. H.; Xu, J. X. Curr. Microw. Chem. 2017,
4, DOI: 10.2174/2213335604666171031142132.
1
2, copies of H and 13C NMR spectra of diazo compounds 2,
oxiranes 4, and products 5, and copies of HPLC profiles for the
enantiomeric excessive determination of products (R)-5f. The
Supplementary Material is available free of charge on http://dx.
doi: 10.1021/xxxxxx.
19. (a) Xu, J. X. Prog. Chem. 2007, 19, 700. (b) Li, X. H.; Xu, J. X.
Tetrahedron 2016, 72, 5515.
References
1.
2.
Sehnging, B.; Kulka, M. Science 1966, 152, 659.
(a) Asinger, F.; Sans, A.; Offermanns, H.; Scherberieh, P. Liebigs Ann.
Chem. 1971, 753, 151. (b) Kulka, M. Can. J. Chem. 1980, 58, 2044. (c)
White, G. A.; Thorn, G. D. Pestic. Biochem. Physi. 1975, 5, 380. (d)
Reinbergs, E.; Edgington, L. V.; Metcalfe, D. R.; Bendelow, V. M. Can.
J. Chem. 1968, 48, 31.
3.
Bader, J. P.; McMahon, J. B.; Schultz, R. J.; Narayanan, V. L.; Pierce, J.
B.; Harrison, W. A.; Weislow, O. S.; Midelfort, C. F.; Stinson, S. F.;
Boyd, M. R.. Proc. Natl. Acad. Sci. USA. 1991, 88, 6740.
Dekeyser, M. A.; Davis, R. A. J. Agric. Food Chem. 1998, 46, 2827.
Ferreira, R. S.; Simeonov, A.; Jadhav, A.; Eidam, O.; Mott, B. T.;
Michael J. Keiser, M. J.; James H. McKerrow, J. H.; Maloney, D. J.;
Irwin, J. J.; Shoichet, B. K. J. Med. Chem. 2010, 53, 4891.
(a) Balzarini, J.; Jonckheere, H.; Harrison, W. A.; Dao, D. C.; Anne, J.;
Clercq, E.; Karlsson, A. Antiviral. Chem. Chemother. 1995, 6, 169. (b)
Ji, X. S.; Wang, Y. L.; Zhang, H. F.; Gao, Y.; Liu, Z. Y.; Wang, J. K. J.
Chin. Pharm. Sci. 2000, 9, 179. (c) Davis, R. A.; Grahame, R. E.;
Kulka, M. U.S. Patent 3657449, 1972.
4.
5.
6.
7.
Kissane, M.; Murphy, M.; O'Brien, E.; Chopra, J.; Murphy, L.;
Collins ,S. G.; Lawrence, S. E.; Maguire, A. R. Org. Biomol. Chem.
2011, 9, 2452.
8.
9.
Capozzi, G.; Meniehetti, S.; Nativi, C.; Rosi, A.; Frauck, R. W.
Tetrahedron Lett. 1993, 34, 4253.
Hahn, H. G.; Chang, K. H.; Nam, K. D.; Bae, S. Y.; Mah, H. J.
Heterocycl. Chem. 2000, 37, 1003
10. Blanchot, V.; Fetizon, M.; Hanna, I. Synthesis 1990, 9, 755.
11. Achard, T.; Tortoreto, C.; Poblador-Bahamonde, A. I.; Guénée, L.;
Bürgi, T.; Lacour, J. Angew. Chem. Int. Ed. 2014, 53, 6140.
12. (a) Xu, J. X. Tetrahedron: Asymmetry 2002, 13, 1129. (b) Xu, J. X.;
Xu, S. Synthesis 2004, (2), 276. (c) Huang, J. X.; Wang, F.; Du, D. M.;
Xu, J. X. Synthesis 2005, (13), 2122. (d) Xu, J. X.; Xu, S. Heteroat.
Chem. 2005, 16, 466. (e) Huang, J. X.; Du D M, Xu, J. X. Synthesis
9