A copper-catalyzed reaction between terminal alkynes, acetylenic esters, and oxiranes: efficient synthesis of 2H-pyran-4-carboxylate

Article abstract of DOI:10.1007/s00706-019-02526-z

Abstract: A catalytic reaction between terminal alkynes, acetylenic esters, and oxiranes has been described. This domino transformation serves as a useful sequential and one-pot method for the synthesis of 2H-pyran-4-carboxylate skeletons from the readily available starting materials. In situ-generated copper acetylides treated initially with oxiranes in the presence of copper catalysts and tetrabutylphosphonium salts, followed by addition of propiolates after 60?min to form synthetically important heterocycles. Graphic abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s00706-019-02526-z

Monatshefte für Chemie - Chemical Monthly
https://doi.org/10.1007/s00706-019-02526-z
ORIGINAL PAPER
A copper‑catalyzed reaction between terminal alkynes, acetylenic
esters, and oxiranes: efcient synthesis oꢀ 2H‑pyran‑4‑carboxylate
1
1
2
1
Milad Jahanshad · Mohammadreza Manaf · Seyed Mahmoud Mousavi‑Saꢀavi · Seyed Saied Homami ·
Majid Ghazanꢀarpour‑Darjani3
Received: 7 September 2019 / Accepted: 25 November 2019
©
Springer-Verlag GmbH Austria, part of Springer Nature 2020
Abstract
A catalytic reaction between terminal alkynes, acetylenic esters, and oxiranes has been described. This domino transforma-
tion serves as a useful sequential and one-pot method for the synthesis of 2H-pyran-4-carboxylate skeletons from the read-
ily available starting materials. In situ-generated copper acetylides treated initially with oxiranes in the presence of copper
catalysts and tetrabutylphosphonium salts, followed by addition of propiolates after 60 min to form synthetically important
heterocycles.
Graphic abstract
Keywords Domino reaction · Three-membered heterocycle · Copper catalysis · Acetylenic ester · Cyclization
Introduction
catalytic transformations allow the reactions to be performed
in mild conditions with the use of starting materials that are
not compatible with classical procedures. This is because
of exceptional ability of alkynophile metals to activate
π-electrons of alkynes towards nucleophilic attacks.
Synthesis of heterocyclic compounds is a highly demand-
ing ꢀeld to chemists in the ꢀeld of organic chemistry (for
selected examples of coinage metals-catalyzed synthesis
of heterocycles, see [1–3], [4]). A particularly efficient
method in this ꢀeld is transition-metal-catalyzed electro-
philic cyclization across C–C triple bonds [5–9]. These
For instance, the copper-catalyzed 1,3-cycloaddition of
organic azides and terminal alkynes ꢀx major drawbacks
of the thermal versions likes low rate and regioselectivity
[
10–12]. The great success in copper-catalyzing the Huis-
*
Mohammadreza Manaꢀ
mr_manaꢀ@azad.ac.ir
gen 1,3-dipolar cycloaddition resulted in enormous atten-
tion to explore the precise role of copper salts in activation
of alkyne synthon [13, 14]. These studies shed light on the
mechanism of activation of alkynes and revealed that the
π-electrons of C–C triple bond are strongly coordinated to
copper species through the reaction progress. Considering
the distortion of π-electron’s density across with the C–C tri-
ple bond is the origin of a great number of reports featuring
synthesis of molecular functionality and complexity using
copper acetylides [15–21].
*
Majid Ghazanfarpour-Darjani
m.ghazanfarpour@modares.ac.ir
1
2
3
Department of Applied Chemistry, Faculty of Science, South
Tehran Branch, Islamic Azad University, Tehran, Iran
Department of Chemistry, Buinzahra Branch, Islamic Azad
University, Buinzahra, Iran
Department of Chemistry, Center for Catalysis Research
and Innovation, BAHERENERGY Institute of Technology,
P.O. Box 13487-55613, Tehran, Iran
Vol.:(0
1
123456789)
3

M. Jahanshad et al.
Based on these ꢀndings, we have reported a reaction
involving copper acetylides, carbon disulꢀde, and oxiranes
to form 1,4-oxathianes in good yields and excellent regiose-
lectivity [22]. Subsequently, Samzadeh-Kermani and Khalaj
independently reported a number of methods featuring syn-
thesis of heterocyclic compounds using metal acetylides,
heterocumulenes, and an appropriate third coupling partner
While the reaction between metal acetylides and heterocu-
mulenes, imines, and carbonyls has been well documented,
the conjugated additions of metal acetylides on activated
C–C triple bonds are without precedent. Based on above lit-
eratures and in continuation of our reports in copper cataly-
sis [28–30], we became interested to examine the conjugated
additions of metal acetylides on acetylenic esters in the pres-
ence of oxiranes as third coupling partners toward synthesis
of 2H-pyran molecules (Scheme 1).
[
23–26].
Carriera and co-workers have reported the ꢀrst catalytic
additions of copper acetylides on Michael acceptors [27].
There are many reports in literature featuring synthesis
of 2H-pyran structures with catalytic reactions being among
the most studied procedures [8, 31–33]. Recently, Varmaz-
yar and co-workers have developed a novel catalytic reaction
to form 2H-pyran from catalytic additions of copper acetyl-
ides on oxiranes in the presence of malonates [34]. Accord-
ing to the literature, the regioselectivity in ring opening of
three-membered heterocycles relies on substrates’ structures,
catalysts, and reaction conditions [35–38].
Scheme 1
Table 1 Optimization of reaction conditions
Entry
Catalyst
Base
Additive
Solvent
Yield of 4a/%
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
CuI
CuBr·SMe2
(i-Pr) EtN
TBPAc
TBPAc
TBPAc
TBPAc
TBPAc
TBPAc
TBPAc
TBPAc
TBPAc
TBPAc
TBPAc
TBPAc
TBPAc
TBPAc
TBPAc
TBPAc
TBPCl
TBPBr
TMPAc
TEPAc
TBPAc
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
THF
57
84
67
29
62
53
54
64
2
(i-Pr) EtN
2
Cu O
(i-Pr) EtN
2
2
CuCl
Cu(BF4)2
CuOTf
Cu(OTf)2
(i-Pr) EtN
2
(i-Pr) EtN
2
(i-Pr) EtN
2
(i-Pr) EtN
2
CuBr·SMe2
CuBr·SMe2
CuBr·SMe2
CuBr·SMe2
CuBr·SMe2
CuBr·SMe2
CuBr·SMe2
CuBr·SMe2
CuBr·SMe2
CuBr·SMe2
CuBr·SMe2
CuBr·SMe2
CuBr·SMe2
(i-Pr) EtN
2
(i-Pr) EtN
DMF
HFIP
31
2
0
1
2
3
4
5
6
7
8
9
0
1
(i-Pr) EtN
(61)a
(73)a
Traces
(74)a
69
2
(i-Pr) EtN
PEG-400
Toluene
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
2
(i-Pr) EtN
2
t-BuOLi
Cs CO
2
3
K CO
21
18
15
31
43
59
Traces
2
3
Et N
3
(i-Pr) EtN
2
(i-Pr) EtN
2
(i-Pr) EtN
2
(i-Pr) EtN
2
(i-Pr) EtN
2
3
Reaction conditions: 1a (1.2 mmol), 3a (2.0 mmol), catalyst (0.1 mmol), base (1.5 mmol), additive (0.3 mmol), and 4.0 cm solvent were reacted
at ambient conditions for 1 h, 2a (1.0 mmol) was then added and the mixture was stirred at 70 °C for 16 h
a
The digit in parentheses refer to the yield of 5
1
3

A copper-catalyzed reaction between terminal alkynes, acetylenic esters, and oxiranes:…
Results and discussion
at once, the targeted product 4a was not detected at all (not
shown in Table 1). Additionally, the reaction performed with
TBPAc (1.0 mmol) resulted in formations of alkylated prod-
ucts derived from the reaction of terminal alkyne with TBP
cation. It is worth mentioning that the reaction exhibited
good regioselectivity with respect to the exo-double bond to
aꢁord (Z)-conꢀguration of 6-benzylidene motif.
We initially examined the reaction of phenyl acetylene (1a),
methyl propiolate (2a), and methyl oxirane (3a) under the
catalysis of CuI in MeCN at 70 °C (Table 1). The reaction
performed without an additive only aꢁorded the desired
compound 4a in 7% yield (not shown in Table 1). Based on
the previous reports, we found that tetrabutylphosphonium
salts (TBP) eꢁectively activate three-membered heterocy-
cles towards nucleophilic attacks [39, 40]. Additionally,
alkylphosphonium salts exhibited good catalyst activity in
the presence of propiolates [41]. We believe that the adduct
derived from the reaction of metal acetylide and propiolate
could not attack on oxirane without a preliminary activa-
tion (see Scheme 3). Fortunately, the proposed three-com-
ponent reaction proceeded cleanly and aꢁorded the targeted
compound 4a in reasonable yield using tetrabutylphospho-
nium acetate (TBPA) (entry 1). Encouraged by this result,
we next examined the eꢂciency of diꢁerent catalysts and
The generality of the reaction was then evaluated using
various terminal alkynes and oxiranes (Table 2). The
reaction of 2-methyloxirane (3a) proceeded cleanly and
aꢁorded the desired compound 4a in good yield (entry 1).
Butyl-linked oxirane 3b reacted with a partial decrease
in yield (entry 2). Oxiranes bearing an additional oxygen
atom likes 3c or 3d aꢁorded an excellent yield of the cor-
responding products 4c and 4d (entries 3 and 4). An addi-
tional oxygen atom presumably acts as an auxiliary cata-
lyst coordination site and thereby, activates oxirane toward
subsequent nucleophilic attacks. Expanding the scope of
3 to cyclic oxirane like 3e was also possible, allowing the
formations of fused bicyclic compound 4e in reasonable
yield (entry 5). When phenyl-substituted oxirane 3f was
subjected to the optimum reaction conditions, the ben-
zylic-attacked product 4f was formed exclusively (entry
6). 4-Chlorophenyl and p-tolyl oxiranes (3g, 3h) engaged
proꢀciently in this transformation to furnish correspond-
ing 2H-pyran-4-carboxylates 4g, 4h in acceptable yields
(entries 7 and 8). The reaction with p-tolylacetylene (1b)
aꢁorded an excellent yield (entry 9). It could be deduced
that the attack of copper acetylide on propiolate is the
rate-determination step of this catalytic reaction. Alkyl
terminal alkyne 1c was also tolerated; however, the reac-
tion required higher temperature to aꢁord the expected
product 4j in good yield (entry 10). It should be noted that
highly substituted oxirane 2,2,3,3-tetramethyloxirane (3i)
only aꢁorded the corresponding compound 4k in moderate
yield (entry 11).
CuBr·SMe identiꢀed as the optimum choice for the reac-
2
tion (entries 2–7). It is worth mentioning that the oxidation
states of copper salts did not aꢁect the reaction outcome
in appreciable manner (entry 6 vs. 7). To further optimize
the reaction parameters, we performed the reaction in dif-
ferent solvent and our selected results are shown in Table 1
(
entries 8–12). Interestingly, the reaction conducted in hex-
aꢃuoroisopropanol (HFIP) and PEG-400 (which is known
to activate oxiranes through intermolecular H-bonding [34,
4
2]) formed the direct coupling product 5 in 61% and 73%
yields, respectively (entries 10, 11). The reaction was also
conducted with diꢁerent organic and inorganic bases and
ꢀ
nally, (i-Pr) EtN was selected as the base of choice based
2
on the cost and eꢂciency (entries 13–16). To our delight,
the use of t-BuOLi as an inorganic base resulted in forma-
tion of compound 5 in 74% yield (entry 13). The oxygen
atom in 3a would be coordinated preferably to lithium ion,
thereby providing the opportunity for the direct attack of
copper acetylide on activated oxirane. Inferior results were
obtained using tetrabutylphosphonium chloride or bromides
as an additive (entries 17, 18). Additionally, the success of
the transformation has great dependence on alkyl group of
phosphonium salts; as the reaction conducted with tetra-
methyl- and tetraethylphosphonium acetated aꢁorded 4a
in lower yields (entries 19, 20). As expected, the reaction
without copper catalyst was not productive (entry 21). Based
on the spectroscopic analyses, all of the reactions proceeded
through a 6-exo cyclization route. It is worth mentioning
that no product arising from the attack of acetylides derived
from propiolates are detected in crude reaction mixture
analyses. Importantly, without a preliminary activation of
oxirane, the reaction proceeded in two-component mode as
when all the substrates were charged to the reaction vessel
To further demonstrate the utility of the proposed reac-
tion, other propiolates 2b–2j were also examined and the
results are shown in Table 3. The reactions of methyl- and
tert-butyl propiolates (2b, 2c) proceeded smoothly and
aꢁorded the desired 2H-pyran structures in good yields
(entries 1 and 2). The catalytic reaction was partially inhib-
ited by steric hindrance from an additional substituent at
the triple bond; as ethyl but-2-ynoate (2d) and ethyl 3-phe-
nylpropiolate (2e) reacted with a notable decrease in yields
(entries 3 and 4). Interestingly, propiolamide (2f) was also
tolerated (entry 5). The tolerance for propiolamide gives fur-
ther advantage to the present protocol. Additionally, this is in
contrast with previous reports which reported that acetylenic
esters are protonated upon reaction with amides [41, 43].
Electron-rich terminal alkyne 1d eꢁectively participated in
this domino transformation while, alkyne containing CF3 as
motif only aꢁorded a low yield (entries 6 and 7). It could be
1
3

M. Jahanshad et al.
Table 2 Synthesis of functionalized 2H-pyran-4-carboxylates with various oxiranes and alkynes
R1
Oxirane
R ,R
2
3
Yield/%
Entry
Alkyne
1
2
3
4
5
6
7
8
9
1a
1a
1a
1a
1a
1a
1a
1a
1b
1c
1a
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
3a
3b
3c
3d
3e
3f
3g
3h
3a
3a
3i
Me, H, H, H
4a, 84
4b, 79
4c, 93
4d, 90
4e, 72
4f, 85
4g, 87
4h, 67
4i, 90
4j, 72a
4k, 43
n-C H , H, H, H
4
9
PhOCH , H, H, H
2
Me CHOCH , H
2
2
–(CH ) –, H, H
2
4
Ph, H, H, H
4-Cl-C H , H, H, H
6
4
4-Me-C H , H, H, H
6
4
4-Me-C H
CH OCH
Ph
Me, H, H, H
Me, H, H, H
Me, Me, Me, Me
6
4
10
1
3
2
1
For all entries except stated otherwise: 1 (1.2 mmol), 3 (2.0 mmol), CuBr·SMe (0.1 mmol), (i-Pr) EtN (1.5 mmol), TBPAc (0.3 mmol), in
2
2
3
4
.0 cm dry MeCN were stirred at ambient conditions for 1 h, 2a (1.0 mmol) was then added and the mixture was stirred at 70 °C for 16 h
a
At 90 °C
Table 3 Synthesis of functionalized 2H-pyran-4-carboxylates using various alkynes and propiolates
R1
Propiolate
R , R
2
3
Yield/ %
Entry
Alkyne
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1d
1e
1f
Ph
Ph
Ph
Ph
Ph
2b
2c
2d
2e
2f
2b
2b
2b
H, CO Et
4l, 83
2
H, CO t-Bu
4m, 85
4n, 46
4o, 58
4p, 69
4q, 92
4r, 34a
4s, 63
2
Me, CO Et
2
Ph, CO Et
2
H, CONH2
4-MeO-C H
3-CF -C H
n-Bu
H, CO Et
6
4
2
H, CO Et
3
6
4
2
H, CO Et
2
For all entries except stated otherwise: 1 (1.2 mmol), 3a (2.0 mmol), CuBr·SMe (0.1 mmol), (i-Pr) EtN (1.5 mmol), TBPAc (0.3 mmol), in
2
2
3
4
.0 cm dry MeCN were stirred at ambient conditions for 1 h, 2 (1.0 mmol) was then added and the mixture was stirred at 70 °C for 16 h
a
At 90 °C
1
3

A copper-catalyzed reaction between terminal alkynes, acetylenic esters, and oxiranes:…
Scheme 2
Scheme 3
deduced that the nucleophilic attack of metal acetylide on
propiolate is the rate-determination step of this transforma-
tion. 1-Hexyne (1e) was also tolerated, however, the reac-
tion required higher temperature to give the corresponding
product 4s in reasonable yield (entry 8).
not aꢁord the targeted product 4a and instead gave the direct
coupling product 5 (see Table 1, entries 10, 11).
Based on previous reports [27, 29, 30], the possible reac-
tion pathway is proposed in Scheme 4. Coordination of copper
catalyst with phenyl acetylene in the presence of (i-Pr) EtN
2
When chiral oxirane 3f′ was used as the substrate, the
domino ring opening/cyclization reaction proceeded with
racemization at the chiral centre (Scheme 2). This result
gave copper acetylide 6. The nucleophilic attack of in situ-
generated copper acetylide to the propiolate yielded the
adduct 7 which further reacted with activated oxirane (species
8) to form the ring opened-intermediate 9. The electrophilic
indicated that the reaction proceeded through a S 1 pathway
N
using phenyl-substituted oxirane.
cyclization of 9 by the action of copper salt in the presence of
+
To propose a more reliable mechanism for the forma-
tion of 4, some control experiments were performed and the
results are shown in Scheme 3. These results indicate that
TBPAc inhibited formation of the compound I and instead
a polymeric oil was obtained. These ꢀndings deduced that
in the presence of TBPAc the anionic adduct derived from
terminal alkyne and propiolate attacks again on another pro-
piolate while, in the presence of activated oxirane, the reac-
tion proceeded through three-component modes to aꢁord the
desired compound 4a. Additionally, the reaction with com-
pound I and 3a did not aꢁord the desired product 4a at all
while in the presence of a strong base like NaH the reaction
formed compound 4a in good yield. These results are further
supported by the fact that the reaction in protic solvents did
(i-Pr) EtNH aꢁorded the expected 6-exo product 4.
2
Conclusion
In summary, we have reported an eꢂcient reaction between
terminal alkynes, propiolates, and oxiranes as the third cou-
pling partner in the presence of CuBr·SMe as the catalyst
2
and TBPAc as additive to access synthetically important
2H-pyran-4-carboxylate structures. To our knowledge this
is the ꢀrst catalytic additions of copper acetylides on pro-
piolates in the presence of oxiranes. Control experiments
indicated that an inert atmosphere together with TBPAc is
necessary to furnish the transformation in good yield.
1
3

M. Jahanshad et al.
Scheme 4
Experimental
column chromatography on silica gel (eluent gradient of
EtOAc/hexane, see spectroscopic analysis section) to give
the corresponding products 4 in the yields listed in Tables 2
and 3.
3
All reactions were carried out in Schlenk tube (25 cm )
under nitrogen atmosphere. All the reagents, catalysts, and
additives were obtained from commercial sources. All the
solvents were purchased from PALAENERGY Pure Chemi-
cal Industries, and were dried and degassed before use.
Melting points were measured with Electrothermal-9100
apparatus. IR spectra were determined on a Nicolet 6700
Methyl 6‑benzylidene‑2‑methyl‑3,6‑dihydro‑2H‑pyran‑4‑car‑
boxylate (4a, C15H16O3) The crude product was puriꢀed
by column chromatography (SiO2, hexane/EtOAc 9/1,
Rf = 0.29) aꢁording 0.21 g (84%) of 4a. Colorless oil; IR
1
13
−1
spectrometer. H and C NMR spectra were recorded with
(KBr): ̄ꢀ=3022, 2970, 1723, 1644, 1465, 1255, 1121 cm ;
1
3
Bruker DRX-500 AVANCE instrument; in CDCl at 500 and
H NMR (500.1 MHz, CDCl3): δ=1.32 (3H, d, J=6.1 Hz,
3
2
3
1
25 MHz, resp.; δ in ppm, J in Hz. Mass spectra were deter-
Me), 2.41 (1H, dd, J = 12.3 Hz, J = 10.1 Hz, CH), 2.55
2
3
mined on a EIMS (70 eV): Finnigan-MAT-8430 mass spec-
trometer. Elemental analyses were performed with a Her-
aeus Rapid analyser. The results agreed favorably with the
calculated values. Silica gel 60 (particle size 63–200 µm or
(1H, dd, J=12.3 Hz, J=5.2 Hz, CH), 3.72 (3H, s, OMe),
4.00–4.05 (1H, m, CH), 5.24 (1H, s, CH), 7.15 (1H, s, CH),
3
3
7.32 (1H, t, J=7.1 Hz, CH), 7.41 (2H, t, J=7.2 Hz, 2 CH),
3
13
7.64 (2H, d, J=7.3 Hz, 2 CH) ppm; C NMR (125.7 MHz,
CDCl3): δ=23.1 (Me), 40.1 (CH2), 54.6 (OMe), 81.4 (CH),
87.1 (CH), 124.2 (C), 126.5 (CH), 129.4 (2 CH), 130.7 (2
CH), 133.8 (C), 145.1 (CH), 149.7 (C), 167.2 (C) ppm;
4
0–100 mesh) was used for column chromatography (Merck,
item number 7734-3). TLC analyses were performed on
commercial glass plates bearing a 0.25-mm layer of Merck
Silica gel 60 (Merck, item number 116835).
+
EI-MS (70 eV): m/z (%)=244 (M , 1), 229 (12), 177 (23),
1
00 (65), 91 (43), 77 (100), 54 (48).
General procedure for the preparation
of compounds 4
Methyl 6‑benzylidene‑2‑butyl‑3,6‑dihydro‑2H‑pyran‑4‑car‑
boxylate (4b, C H O ) The crude product was puriꢀed
1
8 22 3
3
A Schlenk tube (25 cm ) equipped with a magnetic stir bar
by column chromatography (SiO2, hexane/EtOAc 10/1,
was charged with terminal alkyne (1.2 mmol), (i-Pr) EtN
Rf = 0.35) aꢁording 0.23 g (79%) of 4b. Colorless oil; IR
2
−
1
(
1.5 mmol), CuBr·SMe (0.1 mmol), TBPAc (0.3 mmol),
(KBr): ̄ꢀ=3014, 2973, 1722, 1651, 1473, 1286, 1095 cm ;
2
3
1
3
oxirane (2.0 mmol), and 2.0 cm MeCN. After the mixture
was stirred at 25 °C for 1 h, propiolate (1.0 mmol) was
added under an inert atmosphere. The tube was evacuated
and backꢀlled with argon (three times). Subsequently, the
mixture was stirred for 16 h at appropriate temperature (see
Tables 2, 3). After cooling to room temperature, the mixture
was passed through silica gel pad and concentrated under
reduced pressure. The resulting residue was puriꢀed with
H NMR (500.1 MHz, CDCl3): δ=0.91 (3H, t, J=6.0 Hz,
2
Me), 1.35–1.76 (6H, m, 3 CH2), 2.47 (1H, dd, J=11.8 Hz,
3
2
3
J = 5.0 Hz, CH), 2.65 (1H, dd, J = 11.8 Hz, J = 9.7 Hz,
CH), 3.69 (3H, s, OMe), 4.01–4.05 (1H, m, CH), 5.29 (1H,
3
s, CH), 7.19 (1H, s, CH), 7.31 (1H, t, J=7.6 Hz, CH), 7.40
3
3
(2H, t, J=7.6 Hz, 2 CH), 7.59 (2H, d, J=7.6 Hz, 2 CH)
1
3
ppm; C NMR (125.7 MHz, CDCl3): δ=15.2 (Me), 28.1
(CH2), 30.4 (CH2), 37.9 (CH2), 41.9 (CH2), 55.9 (OMe),
1
3

A copper-catalyzed reaction between terminal alkynes, acetylenic esters, and oxiranes:…
8
0.1 (CH), 94.2 (CH), 122.8 (CH), 126.5 (CH), 128.9 (2
3.35–3.40 (1H, m, CH), 3.72 (3H, s, OMe), 5.31 (1H, s,
3
CH), 130.1 (2 CH), 134.8 (C), 144.1 (CH), 148.4 (C), 168.9
CH), 7.16 (1H, s, CH), 7.32 (1H, t, J=7.8 Hz, CH), 7.41
+
3
3
13
(
C) ppm; EI-MS (70 eV): m/z (%)=286 (M , 1), 229 (6),
(2H, t, J=7.8 Hz), 7.67 (2H, d, J=7.7 Hz, 2 CH) ppm; C
NMR (125.7 MHz, CDCl ): δ=28.1 (CH ), 29.4 (CH ), 32.7
1
39 (48), 91 (43), 81 (87), 77 (100), 54 (48).
3
2
2
(
CH ), 34.2 (CH ), 40.4 (CH), 54.4 (OMe), 81.9 (CH), 91.8
2 2
Methyl 6‑benzylidene‑2‑(phenoxymethyl)‑3,6‑dihy‑
(CH), 127.2 (CH), 129.8 (2 CH), 130.9 (2 CH), 133.5 (C),
135.2 (C), 144.6 (CH), 147.1 (C), 167.0 (C) ppm; EI-MS
dro‑2H‑pyran‑4‑carboxylate (4c, C H O ) The crude prod-
21 20 4
+
uct was puriꢀed by column chromatography (SiO , hexane/
(70 eV): m/z (%)=284 (M , 2), 225 (11), 149 (47), 135 (87),
2
EtOAc 8/1, R = 0.31) aꢁording 0.31 g (93%) of 4c. Yel-
91 (39), 77 (100).
f
low oil; IR (KBr): ̄ꢀ=3030, 2957, 1726, 1644, 1452, 1256,
−1 1
1
117 cm ; H NMR (500.1 MHz, CDCl ): δ=2.52 (1H, dd,
Methyl 6‑benzylidene‑3‑phenyl‑3,6‑dihydro‑2H‑pyran‑4‑car‑
boxylate (4f, C H O ) The crude product was purified
3
2
3
2
J=12.1 Hz, J=9.1 Hz, CH), 2.69 (1H, dd, J=12.1 Hz,
2
0 18 3
3
J = 5.1 Hz, CH), 3.79 (3H, s, OMe), 3.95–4.02 (1H, m,
by column chromatography (SiO , hexane/EtOAc 8/1,
2
2
3
CH), 4.29 (1H, dd, J=11.2 Hz, J=8.2 Hz, CH), 4.36 (1H,
R = 0.27) aꢁording 0.26 g (85%) of 4f. Colorless oil; IR
f
2
3
−1
dd, J=11.2 Hz, J=5.2 Hz, CH), 5.34 (1H, s, CH), 6.87
(KBr): ̄ꢀ=3021, 2981, 1726, 1632, 1482, 1251, 1092 cm ;
3
3
1
(
1H, t, J = 6.9 Hz, CH), 6.93 (2H, d, J = 6.9 Hz, 2 CH),
H NMR (500.1 MHz, CDCl ): δ=3.63 (3H, s, OMe), 4.13–
3
3
2
3
7
.09 (1H, s, CH), 7.21 (2H, t, J=6.9 Hz, 2 CH), 7.34 (1H,
4.18 (1H, m, CH), 4.66 (1H, dd, J=11.9 Hz, J=9.1 Hz,
3
3
2
3
t, J=7.2 Hz, CH), 7.43 (2H, t, J=7.3 Hz, 2 CH), 7.66 (2H,
CH), 4.80 (1H, dd, J=11.9 Hz, J=6.0 Hz, CH), 5.25 (1H,
3
13
3
d, J=7.3 Hz, 2 CH) ppm; C NMR (125.7 MHz, CDCl ):
s, CH), 7.17 (1H, s, CH), 7.23 (2H, d, J=7.6 Hz, 2 CH),
3
3
3
δ = 36.6 (CH ), 54.3 (OMe), 68.8 (CH ), 81.4 (CH), 95.2
7.27 (1H, t, J=7.5 Hz, CH), 7.31 (2H, t, J=7.5 Hz, 2 CH),
2
2
3
3
(
CH), 114.3 (2 CH), 120.7 (CH), 123.8 (C), 127.1 (CH),
7.36 (1H, t, J=7.8 Hz, CH), 7.43 (2H, t, J=7.8 Hz, 2 CH),
3
13
1
28.8 (2 CH), 129.7 (2 CH), 130.1 (2 CH), 133.1 (C), 145.1
7.66 (2H, d, J=7.9 Hz, 2 CH) ppm; C NMR (125.7 MHz,
CDCl ): δ=47.1 (CH), 54.1 (OMe), 78.7 (CH ), 95.1 (CH),
(
CH), 147.4 (C), 160.3 (C), 168.9 (C) ppm; EI-MS (70 eV):
3
2
+
m/z (%)=336 (M , 1), 277 (11), 171 (52), 107 (69), 81 (83),
126.1 (CH), 127.0 (CH), 128.2 (2 CH), 128.8 (2 CH), 129.4
(2 CH), 130.1 (2 CH), 133.1 (C), 142.3 (C), 144.6 (CH),
7
7 (100), 54 (32).
1
45.8 (C), 148.3 (C), 170.5 (C) ppm; EI-MS (70 eV): m/z
+
Methyl 6‑benzylidene‑2‑(isopropoxymethyl)‑3,6‑dihy‑
(%)=306 (M , 2), 247 (10), 171 (47), 91 (38), 81 (86), 77
(100).
dro‑2H‑pyran‑4‑carboxylate (4d, C H O ) The crude prod-
18 22 4
uct was puriꢀed by column chromatography (SiO , hexane/
2
EtOAc 10/1, R =0.21) aꢁording 0.27 g (90%) of 4d. Yellow
Methyl 6‑benzylidene‑3‑(4‑chlorophenyl)‑3,6‑dihy‑
f
oil; IR (KBr): ̄ꢀ=3038, 3012, 2958, 1727, 1639, 1542, 1326,
dro‑2H‑pyran‑4‑carboxylate (4g, C H ClO ) The crude
2
0
17
3
−
1 1
1
118 cm ; H NMR (500.1 MHz, CDCl ): δ=1.21 (6H, d,
product was puriꢀed by column chromatography (SiO ,
3
2
3
2
3
J=6.7 Hz, 2 Me), 2.45 (1H, dd, J=11.1 Hz, J=7.7 Hz,
hexane/EtOAc 7/1, R = 0.34) aꢁording 0.30 g (87%) of
f
2
3
CH), 2.67 (1H, dd, J = 11.1 Hz, J = 5.1 Hz, CH), 3.61
4g. Colorless oil; IR (KBr): ̄ꢀ = 3052, 2972, 1730, 1648,
2
3
−1 1
(
3H, s, OMe), 3.70 (1H, dd, J=11.3 Hz, J=8.0 Hz, CH),
1522, 1267, 1076 cm ; H NMR (500.1 MHz, CDCl ):
3
2
3
3
.84 (1H, dd, J = 11.3 Hz, J = 5.0 Hz, CH), 3.90–3.95
δ=3.74 (3H, s, OMe), 4.05–4.11 (1H, m, CH), 4.60 (1H, dd,
2
3
3
2
(
1H, m, CH), 4.02–4.07 (1H, m, CH), 5.23 (1H, s, CH),
J=12.6 Hz, J=9.0 Hz, CH), 4.81 (1H, dd, J=12.6 Hz,
J=5.2 Hz, CH), 5.34 (1H, s, CH), 7.21 (1H, s, CH), 7.35
3
7
.20 (1H, s, CH), 7.34 (1H, t, J=6.9 Hz, CH), 7.42 (2H,
3
3
3
3
t, J=6.9 Hz, 2 CH), 7.59 (2H, d, J=6.9 Hz, 2 CH) ppm;
(1H, t, J = 7.1 Hz, CH), 7.40 (2H, d, J = 7.1 Hz, 2 CH),
1
3
3
3
C NMR (125.7 MHz, CDCl ): δ=21.5 (2 Me), 36.1 (CH ),
7.45 (2H, d, J=7.8 Hz, 2 CH), 7.52 (2H, t, J=7.8 Hz, CH),
3
2
3
13
5
1
4.9 (OMe), 69.2 (CH ), 74.1 (CH), 83.6 (CH), 89.5 (CH),
7.62 (2H, d, J=7.2 Hz, 2 CH) ppm; C NMR (125.7 MHz,
CDCl ): δ=43.1 (CH), 54.1 (OMe), 76.1 (CH ), 93.2 (CH),
2
23.2 (CH), 126.5 (CH), 128.9 (2 CH), 130.8 (2 CH), 133.4
3
2
(
C), 144.7 (CH), 147.8 (C), 168.2 (C) ppm; EI-MS (70 eV):
126.9 (CH), 128.1 (2 CH), 128.9 (2 CH), 129.6 (2 CH),
+
m/z (%)=302 (M , 3), 250 (8), 229 (43), 171 (68), 81 (85),
129.9 (2 CH), 132.2 (C), 134.1 (C), 139.1 (C), 142.3 (C),
7
7 (100).
145.2 (CH), 145.9 (C), 170.9 (C) ppm; EI-MS (70 eV): m/z
+
(
%)=340 (M , 1), 281 (12), 247 (17), 171 (60), 126 (41),
M e t h y l 2 ‑ b e n z y l i d e n e ‑ 4 a , 5 , 6 , 7 , 8 , 8 a ‑ h e x a h y‑
81 (83), 77 (100).
dro‑2H‑chromene‑4‑carboxylate (4e, C H O ) The crude
1
8 20 3
product was puriꢀed by column chromatography (SiO ,
M e t h y l 6 ‑ b e n z y l i d e n e ‑ 3 ‑ ( p‑ t o l y l ) ‑ 3 , 6 ‑ d i h y ‑
dro‑2H‑pyran‑4‑carboxylate (4h, C H O ) The crude prod-
2
hexane/EtOAc 11/1, R = 0.30) aꢁording 0.20 g (72%) of
f
21 20 3
4
e. Colorless solid; IR (KBr): ̄ꢀ=3033, 2958, 1725, 1624,
uct was puriꢀed by column chromatography (SiO , hexane/
2
−
1 1
1
423, 1238, 1077 cm ; H NMR (500.1 MHz, CDCl ):
EtOAc 9/1, R =0.25) aꢁording 0.21 g (67%) of 4h. Color-
3
f
δ = 1.47–2.05 (8H, m, 4 CH ), 2.83–2.88 (1H, m, CH),
less oil; IR (KBr): ̄ꢀ=3041, 2971, 2942, 1726, 1670, 1482,
2
1
3

M. Jahanshad et al.
−
1
1
3
1
252, 1075 cm ; H NMR (500.1 MHz, CDCl ): δ=2.31
(3H, d, J = 5.7 Hz, Me), 1.36 (6H, s, 2 Me), 1.45 (6H, s,
3
3
(
3H, s, Me), 3.66 (3H, s, OMe), 3.92–3.98 (1H, m, CH),
2 Me), 4.21 (2H, q, J=5.7 Hz, OCH ), 5.45 (1H, s, CH),
2
2
3
3
4
.61 (1H, dd, J = 12.5 Hz, J = 8.2 Hz, CH), 4.80 (1H,
7.05 (1H, s, CH), 7.33 (1H, t, J=7.8 Hz, CH), 7.43 (2H,
2
3
3
3
dd, J=12.5 Hz, J=4.9 Hz, CH), 5.25 (1H, s, CH), 7.02
t, J=7.8 Hz, 2 CH), 7.61 (2H, d, J=7.8 Hz, 2 CH) ppm;
3
3
13
(
2H, d, J=7.4 Hz, 2 CH), 7.17 (2H, d, J=7.4 Hz, 2 CH),
C NMR (125.7 MHz, CDCl ): δ=13.9 (Me), 21.8 (2 Me),
3
3
7
.24 (1H, s, CH), 7.33 (1H, t, J=7.3 Hz, CH), 7.44 (2H,
30.1 (2 Me), 53.2 (C), 62.2 (OCH ), 90.5 (C), 93.1 (CH),
2
3
3
d, J=7.3 Hz, 2 CH), 7.65 (2H, d, J=7.1 Hz, 2 CH) ppm;
126.4 (CH), 128.9 (2 CH), 129.7 (2 CH), 133.6 (C), 143.4
1
3
C NMR (125.7 MHz, CDCl ): δ=22.7 (CH ), 40.9 (CH),
(CH), 148.2 (C), 149.5 (C), 168.9 (C) ppm; EI-MS (70 eV):
3
3
+
5
5.6 (OMe), 79.8 (CH ), 89.2 (CH), 126.2 (2 CH), 126.8
m/z (%)=300 (M , 1), 255 (5), 225 (32), 199 (48), 109 (87),
2
(
CH), 128.1 (2 CH), 129.8 (2 CH), 130.3 (2 CH), 134.4 (C),
77 (100).
1
1
36.1 (C), 137.2 (C), 143.9 (C), 145.1 (CH), 146.3 (CH),
+
70.1(C) ppm; EI-MS (70 eV): m/z (%)=320 (M , 3), 290
Ethyl 6‑benzylidene‑2‑methyl‑3,6‑dihydro‑2H‑pyran‑4‑car‑
boxylate (4l, C H O ) The crude product was purified
(
9), 261 (21), 171 (61), 128 (49), 81 (87), 77 (100).
1
6 18 3
by column chromatography (SiO , hexane/EtOAc 10/1,
2
Methyl 6‑(4‑methylbenzylidene)‑2‑methyl‑3,6‑dihy‑
R = 0.36) aꢁording 0.21 g (83%) of 4l. Colorless oil; IR
f
dro‑2H‑pyran‑4‑carboxylate (4i, C H O ) The crude prod-
(KBr): ̄ꢀ = 3015, 2951, 1727, 1611, 1547, 1312, 1276,
1
6 18 3
−
1 1
uct was puriꢀed by column chromatography (SiO , hexane/
1032 cm ; H NMR (500.1 MHz, CDCl ): δ=1.25 (3H, t,
2
3
3
2
3
3
3
EtOAc 8/1, R =0.32) aꢁording 0.23 g (90%) of 4i. Yellow
J=5.6 Hz, Me), 1.34 (3H, d, J=5.9 Hz, Me), 2.53 (1H, dd,
f
3
2
oil; IR (KBr): ̄ꢀ = 3019, 2942, 1727, 1621, 1542, 1466,
J=12.1 Hz, J=9.1 Hz, CH), 2.74 (1H, dd, J=12.1 Hz,
J = 5.0 Hz, CH), 3.97–4.03 (1H, m, CH), 4.12 (2H, q,
−
1 1
1
258, 1109 cm ; H NMR (500.1 MHz, CDCl ): δ=1.30
3
3
(
3H, d, J = 5.8 Hz, Me), 2.34 (3H, s, Me), 2.61 (1H, dd,
J = 5.6 Hz, OCH ), 5.32 (1H, s, CH), 7.19 (1H, s, CH),
2
2
3
2
3
3
J=12.5 Hz, J=8.2 Hz, CH), 2.80 (1H, dd, J=12.5 Hz,
7.35 (1H, t, J=7.3 Hz, CH), 7.40 (2H, t, J=7.3 Hz, 2 CH),
3
3
13
J=4.9 Hz, CH), 3.69 (3H, s, OMe), 3.92–3.98 (1H, m, CH),
7.66 (2H, d, J=7.3 Hz, 2 CH) ppm; C NMR (125.7 MHz,
CDCl ): δ=15.8 (Me), 23.3 (Me), 40.6 (CH ), 63.8 (OCH ),
3
5
2
.29 (1H, s, CH), 7.25 (1H, s, CH), 7.41 (2H, d, J=7.4 Hz,
3
2
2
3
13
CH), 7.63 (2H, d, J = 7.4 Hz, 2 CH) ppm; C NMR
83.2 (CH), 90.6 (CH), 122.2 (C), 126.9 (CH), 128.7 (2 CH),
(
125.7 MHz, CDCl ): δ=22.1 (Me), 24.7 (Me), 40.9 (CH ),
129.5 (2 CH), 134.2 (C), 145.7 (CH), 147.6 (C), 170.5 (C)
3
2
+
5
5.6 (OMe), 82.8 (CH), 93.2 (CH), 122.9 (CH), 128.2 (2
ppm; EI-MS (70 eV): m/z (%)=258 (M , 3), 243 (9), 215
CH), 129.8 (2 CH), 130.5 (C), 138.1 (C), 144.7 (CH), 145.3
(15), 171 (63), 91 (43), 81 (85), 77 (100).
+
(
C), 169.3 (C) ppm; EI-MS (70 eV): m/z (%)=258 (M , 3),
2
43 (8), 213 (21), 185 (51), 81 (83), 77 (100).
tert‑ B u t y l 6 ‑ b e n z y l i d e n e ‑ 2 ‑ m e t h y l ‑ 3 , 6 ‑ d i h y ‑
dro‑2H‑pyran‑4‑carboxylate (4m, C H O ) The crude prod-
18 22 3
Methyl 6‑(2‑methoxyethylidene)‑2‑methyl‑3,6‑dihy‑
uct was puriꢀed by column chromatography (SiO , hexane/
2
dro‑2H‑pyran‑4‑carboxylate (4j, C H O ) The crude prod-
EtOAc 8/1, R =0.19) aꢁording 0.24 g (85%) of 4m. Pale yel-
1
1
16
4
f
uct was puriꢀed by column chromatography (SiO , hex-
low oil; IR (KBr): ̄ꢀ=3022, 2941, 1729, 1614, 1547, 1287,
2
−
1 1
ane/EtOAc 11/1, R = 0.24) aꢁording 0.15 g (72%) of 4j.
1211, 1098 cm ; H NMR (500.1 MHz, CDCl ): δ=1.30
f
3
3
Colorless oil; IR (KBr): ̄ꢀ=3042, 2972, 1728, 1671, 1523,
(3H, d, J=5.9 Hz, Me), 1.52 (9H, s, 3 Me), 2.56 (1H, dd,
−
1
1
2
3
3
2
1
471, 1276, 1092 cm ; H NMR (500.1 MHz, CDCl ):
J=11.8 Hz, J=9.4 Hz, CH), 2.73 (1H, dd, J=11.8 Hz,
3
3
2
δ=1.28 (3H, d, J=6.2 Hz, Me), 2.58 (1H, dd, J=12.0 Hz,
J=5.3 Hz, CH), 4.08–4.14 (1H, m, CH), 5.30 (1H, s, CH),
3
2
3
3
J = 8.5 Hz, CH), 2.79 (1H, dd, J = 12.0 Hz, J = 5.1 Hz,
7.16 (1H, s, CH), 7.34 (1H, t, J=7.0 Hz, CH), 7.43 (2H,
3
3
CH), 3.46 (3H, s, OMe), 3.64 (3H, s, OMe), 3.91–3.96 (1H,
t, J=7.0 Hz, 2 CH), 7.65 (2H, d, J=7.0 Hz, 2 CH) ppm;
1
3
m, CH), 4.17 (2H, s, CH ), 5.07 (1H, s, CH), 7.21 (1H, s,
C NMR (125.7 MHz, CDCl ): δ=23.1 (Me), 30.3 (3 Me),
2
3
1
3
CH) ppm; C NMR (125.7 MHz, CDCl ): δ=23.5 (Me),
39.3 (CH ), 80.2 (C), 82.7 (CH), 90.4 (CH), 122.9 (C), 126.3
3
2
4
0.8 (CH ), 54.2 (OMe), 57.1 (OMe), 70.1 (CH ), 82.3
(CH), 128.2 (2 CH), 130.1 (2 CH), 134.8 (C), 145.1 (CH),
2
2
+
(
(
CH), 111.8 (CH), 123.1 (C), 145.7 (C), 151.2 (C), 169.1
148.7 (C), 170.1 (C) ppm; MS: m/z (%)=286 (M , 4), 271
+
C) ppm; EI-MS (70 eV): m/z (%)=212 (M , 3), 181 (14),
(9), 215 (18), 125 (60), 91 (32), 81 (88), 77 (100), 58 (90).
1
67 (28), 109 (55), 81 (100).
E t h y l 6 ‑ b e n z y l i d e n e ‑ 2 , 5 ‑ d i m e t h y l ‑ 3 , 6 ‑ d i h y ‑
Ethyl 6‑benzylidene‑2,2,3,3‑tetramethyl‑3,6‑dihy‑
dro‑2H‑pyran‑4‑carboxylate (4n, C H O ) The crude prod-
1
7 20 3
dro‑2H‑pyran‑4‑carboxylate (4k, C H O ) The crude
uct was puriꢀed by column chromatography (SiO , hexane/
1
9
24
3
2
product was puriꢀed by column chromatography (SiO ,
EtOAc 12/1, R =0.24) aꢁording 0.12 g (46%) of 4n. Color-
2
f
hexane/EtOAc 8/1, R =0.31) aꢁording 0.21 g (43%) of 4k.
less solid; m.p.: 88–90 °C; IR (KBr): ̄ꢀ=3031, 2943, 1724,
f
−
1 1
Colorless oil; IR (KBr): ̄ꢀ=3035, 2977, 1730, 1601, 1476,
1608, 1550, 1302, 1276, 1085 cm ; H NMR (500.1 MHz,
−
1
1
3
1
245, 1187 cm ; H NMR (500.1 MHz, CDCl ): δ=1.27
CDCl ): δ = 1.20 (3H, t, J = 5.8 Hz, Me), 1.29 (3H, d,
3
3
1
3

A copper-catalyzed reaction between terminal alkynes, acetylenic esters, and oxiranes:…
3
2
3
−1 1
J = 5.6 Hz, Me), 2.62 (1H, dd, J = 11.8 Hz, J = 9.9 Hz,
1264, 1187, 1034 cm ; H NMR (500.1 MHz, CDCl ):
3
2
3
3
3
CH), 2.75 (1H, dd, J=11.8 Hz, J=5.8 Hz, CH), 2.83 (3H,
δ=1.18 (3H, t, J=5.7 Hz, Me), 1.28 (3H, d, J=5.9 Hz,
3
2
3
s, Me), 3.89–3.94 (1H, m, 1 CH), 4.28 (2H, q, J=5.8 Hz,
Me), 2.62 (1H, dd, J=12.8 Hz, J=5.2 Hz, CH), 2.66 (1H,
3
2
3
CH ), 5.30 (1H, s, CH), 7.35 (2H, t, J=7.4 Hz, 2 CH), 7.43
dd, J = 12.8 Hz, J = 10.0 Hz, CH), 3.90 (3H, s, OMe),
2
3
3
3
(
1H, t, J = 7.4 Hz, CH), 7.61 (2H, d, J = 7.4 Hz, 2 CH)
3.95–4.01 (1H, m, 1 CH), 4.27 (2H, q, J = 5.7 Hz, CH ),
2
1
3
3
ppm; C NMR (125.7 MHz, CDCl ): δ=10.3 (Me), 13.9
5.30 (1H, s, CH), 7.13 (2H, d, J=7.8 Hz, 2 CH), 7.19 (1H,
3
3
13
(
(
Me), 24.2 (Me), 38.2 (CH ), 64.7 (CH ), 81.1 (CH), 93.5
s, CH), 7.68 (2H, d, J = 7.8 Hz, 2 CH) ppm; C NMR
(125.7 MHz, CDCl ): δ=15.3 (Me), 24.7 (Me), 40.2 (CH ),
2
2
CH), 126.7 (CH), 128.2 (2 CH), 129.1 (2 CH), 130.3 (C),
3
2
1
33.8 (C), 151.1 (C), 159.3 (C), 169.2 (C) ppm; MS: m/z
58.3 (OMe), 64.6 (CH ), 81.6 (CH), 93.8 (CH), 114.5 (2
2
+
(
(
%)=272 (M , 1), 257 (17), 229 (9), 215 (34), 171 (66), 81
85), 77 (100).
CH), 122.7 (C), 125.8 (C), 133.2 (2 CH), 144.1 (CH), 160.1
+
(C), 169.2 (C) ppm; MS: m/z (%)=288 (M , 2), 272 (11),
1
67 (53), 153 (31), 107 (100), 81 (72), 77 (89).
Ethyl 6‑benzylidene‑2‑methyl‑5‑phenyl‑3,6‑dihy‑
dro‑2H‑pyran‑4‑carboxylate (4o, C H O ) The crude
Ethyl 2‑methyl‑6‑[3‑(triꢁuoromethyl)benzylidene]‑3,6‑di‑
2
2 22 3
product was puriꢀed by column chromatography (SiO ,
hydro‑2H‑pyran‑4‑carboxylate (4r, C H F O ) The crude
2
17 17 3 3
hexane/EtOAc 8/1, R = 0.28) aꢁording 0.19 g (58%) of
product was puriꢀed by column chromatography (SiO ,
f
2
4
o. Pale yellow solid; m.p.: 73–75 °C; IR (KBr): ̄ꢀ=3042,
hexane/EtOAc 3/1, R = 0.46) aꢁording 0.11 g (34%) of
f
−
1 1
2
951, 1739, 1604, 1554, 1311, 1256, 1051 cm ; H NMR
4r. Colorless solid; m.p.: 91–93 °C; IR (KBr): ̄ꢀ = 3043,
3
−1 1
(
500.1 MHz, CDCl ): δ = 1.14 (3H, t, J = 5.5 Hz, Me),
2989, 1730, 1537, 1521, 1276, 1240, 1082 cm ; H NMR
3
3
2
3
1
.31 (3H, d, J = 5.4 Hz, Me), 2.54 (1H, dd, J = 11.5 Hz,
(500.1 MHz, CDCl ): δ = 1.13 (3H, t, J = 5.6 Hz, Me),
3
3
2
3
3
2
J = 9.2 Hz, CH), 2.66 (1H, dd, J = 11.5 Hz, J = 5.2 Hz,
1.31 (3H, d, J = 5.6 Hz, Me), 2.58 (1H, dd, J = 12.3 Hz,
3
3
2
3
CH), 3.97–4.04 (1H, m, 1 CH), 4.31 (2H, q, J = 5.5 Hz,
J = 5.5 Hz, CH), 2.74 (1H, dd, J = 12.3 Hz, J = 9.6 Hz,
3
3
CH ), 5.36 (1H, s, CH), 7.20 (2H, d, J = 7.6 Hz, 2 CH),
CH), 3.93–4.00 (1H, m, 1 CH), 4.33 (2H, q, J = 5.6 Hz,
2
3
3
7
.30–7.46 (6H, m, 6 CH), 7.64 (2H, d, J=7.4 Hz, 2 CH)
CH ), 5.48 (1H, s, CH), 7.17 (1H, t, J=7.9 Hz, CH), 7.23
2
1
3
3
ppm; C NMR (125.7 MHz, CDCl ): δ=15.9 (Me), 25.1
(1H, s, CH), 7.41 (1H, d, J = 7.9 Hz, CH), 7.40 (1H, s,
3
3
(
(
Me), 40.5 (CH ), 64.1 (CH ), 83.4 (CH), 93.2 (CH), 116.8
CH), 7.53 (1H, s, CH), 7.70 (1H, d, J=7.9 Hz, CH) ppm;
2
2
1
3
C), 126.3 (CH), 126.8 (CH), 128.5 (2 CH), 128.9 (2 CH),
C NMR (125.7 MHz, CDCl ): δ=15.5 (Me), 22.9 (Me),
3
1
29.4 (2 CH), 130.1 (2 CH), 133.1 (C), 134.2 (C), 149.3 (C),
40.9 (CH ), 65.2 (CH ), 81.9 (CH), 93.2 (CH), 121.2 (C),
2 2
+
3
3
1
57.4 (C), 169.4 (C) ppm; MS: m/z (%)=334 (M , 2), 319
123.6 (CH, q, J=4.8 Hz), 124.5 (CH, q, J=4.8 Hz), 126.2
1
(
6), 291 (15), 247 (68), 157 (42), 81 (79), 77 (100).
(CF , q, J=270.2 Hz), 127.1 (CH), 131.8 (CH), 132.2 (C,
3
2
q, J = 32.9 Hz), 136.1 (C), 144.1 (CH), 146.8 (C), 170.3
+
6
‑Benzylidene‑2‑methyl‑3,6‑dihydro‑2H‑pyran‑4‑carbox‑
(C) ppm; MS: m/z (%)=326 (M , 1), 311 (7), 283 (21), 239
amide (4p, C H NO ) The crude product was purified
(52), 159 (32), 81 (100).
1
4
15
2
by column chromatography (SiO , hexane/EtOAc 4/1,
2
R =0.28) aꢁording 0.16 g (69%) of 4p. Pale yellow solid;
Ethyl 2‑methyl‑6‑pentylidene‑3,6‑dihydro‑2H‑pyran‑4‑car‑
boxylate (4s, C H O ) The crude product was puriꢀed
f
m.p.: 84–86 °C; IR (KBr): ̄ꢀ=3016, 2955, 1637, 1603, 1531,
1
4 22 3
−
1 1
1
308, 1278, 1068 cm ; H NMR (500.1 MHz, CDCl ):
by column chromatography (SiO , hexane/EtOAc 10/1,
3
2
3
δ=1.30 (3H, d, J=5.6 Hz, Me), 2.58–2.69 (2H, m, 2 CH),
R = 0.36) aꢁording 0.15 g (63%) of 4s. Colorless oil; IR
f
−
1
3
.93–3.98 (1H, m, CH), 5.32 (1H, s, CH), 6.83 (2H, br s,
(KBr): ̄ꢀ=3018, 2968, 1726, 1534, 1282, 1132, 1108 cm ;
3
1
3
NH ), 7.18 (1H, s, CH), 7.37 (2H, t, J=7.6 Hz, 2 CH), 7.45
H NMR (500.1 MHz, CDCl ): δ=0.89 (3H, t, J=6.2 Hz,
2
3
3
3
3
3
(
1H, t, J=7.6 Hz, CH), 7.66 (2H, t, J=7.6 Hz, 2 CH) ppm;
Me), 1.14 (3H, t, J=5.9 Hz, Me), 1.30 (3H, d, J=5.6 Hz,
1
3
C NMR (125.7 MHz, CDCl ): δ=24.6 (Me), 41.1 (CH ),
Me), 1.37–1.54 (4H, m, 2 CH ), 2.21–2.32 (2H, m, CH ),
3
2
2
2
2
3
8
3.3 (CH), 92.7 (CH), 125.8 (CH), 126.7 (CH), 127.2 (2
2.67 (1H, dd, J=12.0 Hz, J=9.7 Hz, CH), 2.81 (1H, dd,
2
3
3
3
2
CH), 129.1 (2 CH), 134.1 (C), 145.7 (CH), 147.1 (C), 173.2
J=12.0 Hz, J=5.7 Hz, CH), 3.18 (1H, dd, J=12.8 Hz,
J = 5.2 Hz, CH), 3.89–3.94 (1H, m, CH), 4.25 (2H, q,
+
(
C) ppm; MS: m/z (%)=229 (M , 1), 214 (11), 199 (56), 171
3
(
38), 81 (82), 77 (100).
J=5.9 Hz, CH), 4.87 (1H, t, J=5.2 Hz, CH), 7.21 (1H, s,
1
3
CH) ppm; C NMR (125.7 MHz, CDCl ): δ= 13.7 (Me),
3
Ethyl 6‑(4‑methoxybenzylidene)‑2‑methyl‑3,6‑dihy‑
15.2 (Me), 23.6 (Me), 25.1 (CH ), 28.3 (CH ), 35.4 (CH ),
2
2
2
dro‑2H‑pyran‑4‑carboxylate (4q, C H O ) The crude prod-
39.8 (CH ), 64.7 (CH ), 83.2 (CH), 110.7 (CH), 122.5 (C),
17
20
4
2 2
uct was puriꢀed by column chromatography (SiO , hexane/
144.1 (CH), 146.9 (C), 169.1 (C) ppm; MS: m/z (%)=238
2
+
EtOAc 8/1, R = 0.22) aꢁording 0.26 g (92%) of 4q. Pale
(M , 1), 223 (9), 195 (25), 151 (58), 81 (100), 71 (83).
f
yellow oil; IR (KBr): ̄ꢀ = 3042, 2989, 1724, 1603, 1534,
1
3

M. Jahanshad et al.
Acknowledgements We wish to thank for a grant from Islamic Azad
22. Ghazanfarpour-Darjani M, Babapour-Kooshalshahi M, Mousavi-
Safavi SM, Akbari-Neyestani J, Khalaj M (2016) Synlett 27:259
University, South Tehran Branch.
2
2
2
3. Samzadeh-Kermani A (2019) J Heterocycl Chem 56:450
4. Samzadeh-Kermani A (2019) J Sulfur Chem 40:554
5. Khalaj M, Sadeghpour M, Mousavi Safavi SM, Lalegani A,
Khatami SM (2019) Monatsh Chem 150:1085
References
2
6. Samzadeh-Kermani A (2015) Synlett 26:643
1
2
.
.
Patil NT, Yamamoto Y (2008) Chem Rev 14:3395
27. Knöpfel TF, Carreira EM (2003) J Am Chem Soc 125:6054
28. Ghazanfarpour-Darjani M, Barat-Seftejani F, Khalaj M, Mousavi-
Safavi SM (2017) Helv Chem Acta 100:e1700082
29. Khalaj M, Ghazanfarpour-Darjani M (2017) Synlett 28:1445
30. Yavari I, Ghazanfarpour-Darjani M, Bayat MJ, Malekafzali A
(2014) Synlett 25:959
Echavarren AM, Jiaoc N, Gevorgyand V (2016) Chem Soc Rev
4
5:4445
3
4
.
.
Carabineiro SAC (2016) Molecules 21:746
Martins MAP, Frizzo CP, Moreira DN, Buriol L, Machado P
(
2009) Chem Rev 109:4140
5
6
.
.
Molinaro C, Jamison TF (2003) J Am Chem Soc 125:8076
Jia C, Piao D, Oyamada J, Lu W, Kitamura T, Fujiwara Y (2000)
Science 287:1992
31. Crawley GC, Dowell RI, Edwards PN, Foster SJ, McMillan RM,
Walker ERH, Waterson D, Bird TGC, Bruneau P, Girodeau JM
(1992) J Med Chem 35:2600
7
.
Madhushaw RJ, Lin MY, Sohel SMA, Liu RS (2004) J Am Chem
Soc 126:6895
32. Schmidt B (2003) Eur J Org Chem 2003:816
33. Liang G, Sharum DT, Lam T, Totah NI (2013) Org Lett 15:5974
34. Varmazyar A, Sedaghat S, Goli-Khand AN, Khalaj M, Arab-Sal-
manabadi A (2019) Mol Divers. https://doi.org/10.1007/s1103
0-019-09978-9
8
9
.
.
Fujino D, Yorimitsu H, Osuka A (2014) J Am Chem Soc 136:6255
Verma AK, Kesharwani T, Singh J, Tandon V, Larock RC (2009)
Angew Chem Int Ed 48:1138
1
1
1
1
0. Whiting M, Fokin VV (2006) Angew Chem Int Ed 45:3157
1. Meldal M, Tornøe CW (2008) Chem Rev 108:2952
2. Huisgen R (1989) Pure Appl Chem 61:613
35. Zhou C, Xu JX (2011) Prog Chem 23:174
36. Li X, Xu J (2011) Tetrahedron 67:1681
37. Yub H, Caob S, Zhangc L, Liuc G, Xu J (2009) Synthesis
2009:2205
3. Himo F, Lovell T, Hilgraf R, Rostovtsev VV, Noodleman L,
Sharpless KB, Fokin VV (2005) J Am Chem Soc 127:210
4. Straub BF (2007) Chem Commun 2007:3868
5. Patil NT, Raut VS (2010) J Org Chem 75:6961
6. Yooa WJ, Lia CJ (2008) Adv Synth Catal 350:1503
7. Potuganti GR, Indukuri DR, Nanubolu JB, Alla M (2018) J Org
Chem 83:15186
38. Gálvez JA, de Villegas MDD, Badorreya R, López-Ram-de-Víua
P (2011) Org Biomol Chem 9:8155
1
1
1
1
39. Samzadeh-Kermani A, Zamernaz S (2017) Monatsh Chem
148:1753
40. Samzadeh-Kermani A (2019) Monatsh Chem 150:1495
41. Samzadeh-Kermani A (2016) Synlett 27:2213
42. Kumaraswamy G, Ankamma K, Pitchaiah A (2007) J Org Chem
72:9822
1
1
8. de Armas P, Tejedor D, Garcia-Tellado F (2009) Angew Chem Int
Ed 48:2
9. Varmazyar A, Nozad Goli-Kand A, Sedaghat S, Khalaj M, Arab-
Salmanabadi S (2019) J Heterocycl Chem 56:1850
0. Ramanathan D, Pitchumani K (2015) J Org Chem 80:10299
1. Samzadeh-Kermani A, Ghasemi S (2019) J Heterocycl Chem
43. Yavari I, Ghazanfarpour-Darjani M, Sabbaghan M, Hossaini Z
(2007) Tetrahedron Lett 48:3749
2
2
Publisher’s Note Springer Nature remains neutral with regard to
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jurisdictional claims in published maps and institutional aꢂliations.
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