Domino Processes of Arynes Reacting with Three Classes of Nucleophiles for Organic Syntheses

Article abstract of DOI:10.1002/ejoc.202001499

Synthetic application of arynes is broadened by their reactions with neutral N-, S-, and O-containing nucleophiles to produce three types of compounds. Accordingly, 1,2-dihydroquinolines are synthesized from Schiff bases, alkynes, and arynes through a Diels-Alder reaction. Epoxides are prepared from thioethers and arynes along with aldehydes or ketones through a Johnson-Corey-Chaykovsky reaction. Phenolic ethers are produced from allyl ethers and arynes through a Claisen-type rearrangement. These target molecules, including natural products γ-asarone, asaricin, and a cholesteryl phenolic ether, are formed through reactions initiated by arynes. These new reactions share a prevailing feature of domino processes, which are carried out in a single flask and afford the desired products in good to high yields.

Full text of DOI:10.1002/ejoc.202001499

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Domino Processes of Arynes Reacting with Three Classes of
Nucleophiles for Organic Syntheses
Jih Ru Hwu,*[a] Avijit Panja,[a] Nitesh K. Gupta,[a] Yu-Chen Hu,[b] Kui-Thong Tan,[a]
Chun-Cheng Lin,[a] Kuo-Chu Hwang,[a] Ming-Hua Hsu,[c] Wen-Chieh Huang,[a] and
Shwu-Chen Tsay[a]
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Synthetic application of arynes is broadened by their reactions
with neutral N-, S-, and O-containing nucleophiles to produce
three types of compounds. Accordingly, 1,2-dihydroquinolines
are synthesized from Schiff bases, alkynes, and arynes through
a Diels-Alder reaction. Epoxides are prepared from thioethers
and arynes along with aldehydes or ketones through a
Johnson-Corey-Chaykovsky reaction. Phenolic ethers are pro-
duced from allyl ethers and arynes through a Claisen-type
rearrangement. These target molecules, including natural
products γ-asarone, asaricin, and a cholesteryl phenolic ether,
are formed through reactions initiated by arynes. These new
reactions share a prevailing feature of domino processes, which
are carried out in a single flask and afford the desired products
in good to high yields.
1. Introduction
by treating benzyne with Schiff bases in the presence of CO2.
Our group[8] find that arynes react with two equivalents of Schiff
bases to produce imidazolidines. Furthermore, reaction of
arynes with one equivalent of Schiff bases in the presence of
electron-deficient alkenes generates pyrrolidines.[8] Jugé et al.[9]
develop an efficient method for the preparation of
phosphonium salts by reacting arynes with phosphines. They
are also able to synthesize o-haloaryl P-chirogenic phosphines
from phosphine boranes and haloarynes in the presence of n-
butyllithium.[10] Wang et al.[11] use sulfoxides to react with two
equivalents of benzynes and then N-methyl isatin in situ. The
corresponding spiro[indoline-3,2’-oxiran]-2-ones are produced
in a mixture of cis and trans isomers. Moreover, Richmond and
Spendel[12] find that benzyne cleaves dialkyl ethers in chloro-
form. Yoshida and co-workers[13] disclose that two equivalents
of arynes react with aldehydes to give o-quinones. Herein we
report the feasibility of three unprecedented domino reactions.
The results can add further value[2,3,6] to arynes for their
applications in syntheses of three different classes of com-
pounds shown in Scheme 1.
Arynes are highly reactive intermediates in organic syntheses
and commonly involved in the reactions of bond-insertion,
nucleophilic additions, pericyclic addition, rearrangement, etc.[1]
Recently, Werz and Biju[2] summarize some synthetic applica-
tions of arynes through different insertion and addition
reactions. Ghorai and Lee[3] publish a review article about aryne-
based multicomponent coupling reactions to produce arenes
and heterocycles. Benzynes, the simplest members of arynes,
are in an oxidized form from benzenes[4a,b,5] and generally
function as oxidizing agents. In a few examples, benzynes can
act as reducing agents.[5] Application of arynes is still limited as
harsh conditions are often required for their generation and
thus complicate the sequential reactions to be carried out
in situ.[6] Our laboratory plans to broaden the scope of arynes
for their capability of reacting with neutral nucleophiles that
contain an N-, S-, or O-atom under mild conditions.
Some nucleophiles have been reported to react with arynes
and then the third substrates (if any) in situ to yield different
classes of organic compounds. For example, Yoshida and co-
workers[7] invent a method for the synthesis of benzoxazinones
2. Results and Discussion
[a] Prof. Dr. J. R. Hwu, Dr. A. Panja, Dr. N. K. Gupta, Prof. Dr. K.-T. Tan,
Prof. Dr. C.-C. Lin, Prof. Dr. K.-C. Hwang, Dr. W.-C. Huang, Prof. Dr. S.-C. Tsay
Department of Chemistry and Frontier Research Center on Fundamental
and Applied Sciences of Matters,
2.1. Synthesis of dihydroquinolines through a domino
process including 1,2-elimination, 1,2-addition, and (4+2)
cycloaddition
National Tsing Hua University
Hsinchu 30013, Taiwan
E-mail: jrhwu@mx.nthu.edu.tw
A new method as the first category shown in Scheme 2 was
developed for the synthesis of dihydroquinolines. It involved
the use of silylphenyl triflates 1, Schiff bases 2, and alkynes 3 in
a ratio of 1:1:1 as the starting materials. This reaction was
initiated by use of CsF (1.2 equiv) in THF and carried out at
Homepage: http://chem.site.nthu.edu.tw/p/404-1328-171510.php
[b] Prof. Dr. Y.-C. Hu
Department of Chemical Engineering,
National Tsing Hua University,
Hsinchu 30013, Taiwan
[c] Prof. Dr. M.-H. Hsu
Department of Chemistry,
National Changhua University of Education,
Changhua County 50007, Taiwan
°
40 C for 10–12 hours. Twelve desired 1,2-dihydroquinolines
4a–l were isolated in 75–85% yields.
In this reaction, aryne intermediates were generated from
three different silylphenyl triflates 1a–c. Various Schiff bases
Supporting information for this article is available on the WWW under
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Scheme 1. New methods for the preparation of dihydroquinolines, trans-
epoxides, and phenolic ethers by reaction of arynes with Schiff bases/
alkynes, thioethers/carbonyl compounds, and allyl ethers, respectively.
2a–g had an Me, À OMe, or Cl group attached to the phenyl
group in the =NPh moiety and an Me, OMe, or CO2Me group
attached to the phenyl group in the N=CHPh moiety. The
activated alkynes 3 had two CO2R groups on both ends of the
carbon-carbon triple bond. Such an attachment of electron-
withdrawing groups was found necessary to generate the
desired products 4 in good yields.
The overall pathway for the formation of dihydroquinolines
4 is shown in Scheme 2. It started with a 1,2-elimination in
silylphenyl triflates 1[7,8] by CsF to generate benzynes 5, which
underwent an established 1,2-nucleophilic addition by Schiff
bases 2.[7,8] Then the resultant betaines 6 performed an
unprecedented (4+2) cycloaddition in situ with acetylenes 3 to
produce 1,2-dihydroquinolines 4. Feasibility of this proposed
mechanism is supported by the results of Biju et al.[14] who
report a related (4+2) cycloaddition between betaines and
isatins at their carbonyl group. Furthermore, Coquerel et al.[15]
obtain a mechanism and energy profile of the (4+2) cyclo-
addition between benzyne and N-aryl imines by DFT calcula-
tion. Their computational outcomes support this type of
mechanism proposed by us.
Scheme 2. Generation of 1,2-dihydroquinolines 4 and its plausible mecha-
nism.
4.0–6.0 hours, trans-epoxides 9 were produced as the major or
exclusive products; the by-product was biphenyl thioether (10).
The methylene units in thioethers 7 were directly connected
to a phenyl group (i.e., 7a), which may be attached by an
electron-donating p-OMe group (i.e., 7b) or an electron-with-
drawing p-CO2Me group (i.e., 7c). Most of the epoxides 9 were
obtained in the trans form as the exclusive products in 65–80%
yields except two epoxides 9a and 9b. Their trans isomers were
isolated as the major products along with detection of the
corresponding cis isomers in 18% yield or less. When electron-
withdrawing groups (such as À NO2 and CO2Me) were attached
to the phenyl group in aldehydes 8, yields of the products 9
were improved.
2.2. Preparation of epoxides through a domino process
including 1,2-elimination, 1,2-addition, 1,4-proton shift,
three-membered ring formation, and α-elimination
In the second category, trans-epoxides were formed by reaction
of silylphenyl triflates (1a) with CsF in acetonitrile and then
with phenyl alkyl thioethers 7 and aldehydes 8 in sequence as
°
shown in Scheme 3. After the solution was stirred at 25 C for
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deficient carbonyl group as the substrate yielded the corre-
sponding epoxide 16 (80% yield).
Two equivalents of arynes would react with aldehydes to
give o-quinones.[13] The diversity of our reaction shown in
Scheme 3 involved three-component coupling processes 5a+
1
2
3
4
5
6
7
8
9
7!11 and 12+8!9+10. The thioethers
7 were more
nucleophilic than aldehydes 8[16] and thus had priority to react
with benzynes 5a. As a result, we did not detect any quninone
as the side product in the reaction mixture.
The formation of epoxides 9, 14, and 16 includes sequential
1,2-elimination, 1,2-nucleophilic addition, 1,4-proton shift,[16]
and the Johnson-Corey-Chaykovsky[17,18] reaction (i.e., three-
membered ring formation followed by α-elimination) shown in
Scheme 3. Reactions involving arynes as the intermediates are
sensitive to the media, such as chloroform and acetonitrile.[19]
The protons therein might offer a chance of intermolecular
transfer to the betaine intermediates like 11 through the
pathway “b”. This possible interference, however, was over-
whelmed by the intramolecular 1,4-proton shift pathway “a”,
which led betaines 11 to sulfonium ylides 12.[16] Then three-
membered ring formation followed by α-elimination occurred
sequentially to give the epoxides 9 as the major products and
biphenyl sulfide (10) as the by-product. Peng et al.[20] report
that biphenyl sulfides may undergo nucleophilic addition to
arynes. This process did not impede the early process of 7!11
as biphenyl sulfide was formed at the very last step of 12!9+
10.
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2.3. Synthesis of phenolic ethers through a domino process
including 1,2-elimination, 1,2-addition, and Claisen-type
rearrangement
After applying the nucleophiles containing N- and S-atoms, we
further explored the possibility of neutral O-containing nucleo-
philes in the third category. As shown in Scheme 5, a mixture
containing silylphenyl triflate 1a (1.0 equiv), CsF (1.2 equiv), and
Scheme 3. Generation of trans-epoxides 9 and its plausible mechanism.
°
allyl methyl ether 17a in THF was heated to 50 C for 26 hours.
Furthermore, replacement of aldehydes 8 by cyclic ketones
13a and 13b in the reaction mentioned above led to the
formation of spiro epoxides 14a and 14b, respectively
(Scheme 4). Use of diethyl oxomalonate (15) with an electron-
After separation by flash column chromatography, the product
18a resulting from benzene-insertion was isolated in 71% yield.
When the methyl group in 17a was replaced by a phenyl group
(17b with R7=Ph), o-allyl(phenoxyl)benzenes 18b was obtained
in a lower yield (51%) than that of 18a under thesame reaction
conditions. When an electron-withdrawing group (R8 =-CO2Me)
was attached to the allyl methyl ether 17c, the reaction led to
the product 18c in a very good yield (81%).
Moreover, this reaction was applied to the syntheses of
natural products γ-asarone[21] (18e) and asaricin[22] (18f). Treat-
ment of 1c (R1 =-OMe) with CsF and 17a produced γ-asarone in
60% yield; treatment of 1d (R1 +R1 =-OCH2O) with CsF and 17a
produced asaricin in 58% yield. The use of allyl cholesteryl ether
(17d) as the substrate in this reaction led to the formation of
the corresponding cholesteryl phenolic ether 18g in 52% yield.
Greaney et al. discover a benzyne aza-Claisen rearrange-
ment of tertiary allylamines.[23] They use arynes to provide both
a pi component and to generate a quaternization N-center,
which finally leads to anilines as the products. Ethers are less
Scheme 4. Generation of epoxides 14 and 16 from a silylphenyl triflate,
thioethers, and ketones.
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as n-Bu4F, KF, and KF/18-crown-6, were found not applicable to
1
2
3
4
5
these reactions. Among various solvents, acetonitrile, THF, and
2-Me-THF were found suitable for the generation of the desired
products 4, 9, and 18. All of these three reactions proceeded
°
smoothly under moderate temperatures (25–50 C).
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2.5. Comparison of the three reactions in Scheme 1 with the
established ones
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The new method illustrated in Scheme 2 produced 1,2-
dihydroquinolines in a very efficient way. Some 1,2-dihdroqui-
nolines reported in literature possess anti-allergenic, anti-
cancer,[25] anti-inflammatory, estrogenic, and psychotropic
activities.[26] Several methods have been reported recently for
the syntheses of compounds with closely related scaffolds as
those in compounds 4. For example, Li et al.[27] develop a silver-
catalyzed process for their preparation from anilines and
alkynes. Che et al.[28] report a gold(I)-catalyzed tandem hydro-
amination-hydroarylation involving the use of aromatic amines
and alkynes as the starting materials. Córdova et al.[29] invent an
aza-Michael/Aldol reaction for the asymmetric synthesis of 1,2-
dihydroquinolidines by using organo catalysts. Tamariz et al.[30]
report a solvent-free MgBr2-catalyzed multicomponent reaction.
Rueping and co-workers[31] perform an asymmetric synthesis of
dihydroquinolines through a combined metal catalysis and
organo catalysis process. In comparison with these methods,
our newly developed method shown in Scheme 2 did not
require a catalyst and proceeded smoothly to give the desired
dihydroquinolines in good yields.
Methods for epoxide formation are fruitful in the literature.
A comparison of the method (2) in Scheme 3 with some
established ones is illustrated in Table 1. Our three-component
coupling process involved application of a benzyne intermedi-
ate 5a. It activated thioethers 7 to become zwitterionic
intermediates 11 and 12, in which the Ph2S+-moiety functioned
as a good leaving group during the conversion of 12!9. With
assistance of benzynes, formation of epoxides 9 turned to be
feasible at room temperature with good yields. Xu and Tian[18]
report a method to generate epoxide from tertiary amines
Scheme 5. Generation of phenolic ethers 18 and its plausible mechanism.
nucleophilic than tertiary amines.[23] However, we were able to
allow benzynes 5 to react with alkyl and aryl allylethers 17 to
generate phenolic ethers 18 as the final products. Our design of
this new reaction involved the generation of oxonium phenyl
carbanions 19 as the key intermediate through the process 5+
17!19. The betaines 19 underwent a charge-accelerated
Claisen rearrangement to give allyl ortho-phenolic ethers 18.
Consequently, a sequential 1,2-elimination, 1,2-nucleophilic
addition, and Claisen-type rearrangement took place through a
domino fashion.
°
involving benzyne. The reaction requires 60 C to give epoxides
in 28–90% yields.
For phenolic ether formation shown in Table 1, Sinha
et al.[21] report a three-step method with a 21% overall yield in
the absence of metal catalysts. It has been applied to the
synthesis of natural products, including γ-asarone. The methods
reported separately by Liu et al.[32] and Patil et al.[33] can be
carried out at room temperature in the presence of metal
2.4. Reaction conditions of the three new reactions
°
catalyst. Our method shown in Scheme 5 required 50 C for the
The three new reactions shown in Scheme 1 were performed
individually in a single flask. During optimization of the reaction
conditions, different combinations of reagents were investi-
gated. Use of the Kobayashi’s method[24] for the generation of
arynes from 2-silylaryl triflates 1 and CsF provided the best
results in these three types of new reactions. Generation of
arynes from other compounds, such as halobenzenes, arenedia-
zonium carboxylates, etc., or use of other fluoride sources, such
Claisen-type rearrangement to take place. Without a metal
catalyst present, the reaction led to phenolic ethers in good
yields.
In the three reactions shown in Scheme 1, phenyl moieties
were chosen to be used in substrates including Schiff bases 2,
phenyl alkyl thioethers 7, and aldehydes 8. It was due to the
formation of zwitterionic intermediates with charges at the
appropriate position for ring formations. On the other hand,
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Table 1. Comparison of the three methods shown in Scheme 1 with representative and established methods.
1
2
3
4
5
Product
Method
authors & year
Steps
Temp
Metal-catalyst
Yields
[%]
°
[ C]
1,2-dihydrqinoline
Rueping et al. 2014[31]
Tamariz et al.
2013[30]
1
1
25
yes
yes
47–84
26–99
60–90
6
7
Che et al.
1
150
yes
42–94
2007[28]
present work
Aggarwal et al. 1996[34]
Hwu et al.
2016[35]
1
1
1
40
25
25
no
yes
yes
75–85
38–81
80–91
8
9
epoxide
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
Tian et al.
1
60
no
28–90
2019[18]
present work
Sinha et al.
2002[21]
1
3
25
no
no
60–80
21 overall
phenolic ether
25, 25, 90–120
Patil et al.
1
1
1
25
25
50
yes
yes
no
41–62
81
2017[33]
Liu et al.
2017[32]
present work
51–81
diethyl acetylenedicarboxylate, diethyl oxomalonate, dimethyl
acetylenedicarboxylate (DMAD), 4-methoxybenzaldehyde, 4-meth-
ylbenzaldehyde, and methyl 4-formylbenzoate. The reagents pur-
chased from Sigma-Aldrich included (allyloxy)benzene, benzalde-
this concern was not applicable to the substrates including
alkynes 3 and ethers 17, in which alkyl, allyl, electron-with-
drawing and -donating groups were involved. While the
feasibility of the three reactions was proven, its scope deserves
further studies.
hyde,
3-bromo-4-fluorobenzaldehyde,
3-bromo-4-
methoxybenzaldehyde, 2-chlorobenzaldehyde, 2-fluorobenzalde-
hyde, 3-methoxy-1-propene, 2-nitrobenzaldehyde, and 3-nitroben-
zaldehyde. The reagents purchased from Acros included aniline,
cesium fluoride (CsF), 4-chloroaniline, 4-methoxyaniline, and 4-
methylaniline. The reagents purchased from Tokyo Chemical
Industry Co. included cyclohexanone, cyclopentanone, 4,5-dimeth-
oxy-2-(trimethylsilyl)phenyl trifluoromethanesulfonate, 4,5-dimeth-
yl-2-(trimethylsilyl)phenyl trifluoromethanesulfonate, and 2-
(trimethylsilyl)phenyl trifluoromethanesulfonate.
3. Conclusion
The three synthetic methods shown in Scheme 1 were initiated
by arynes. They underwent nucleophilic attack by a substrate 2,
7, or 17 in the sequential step. The aryne moieties became a
part of the products including dihydroquinolines in Equation (1)
and phenolic ethers in Equation (3). On the other hand, they
served as “unsung heroes” during the formation of epoxides in
Equation (2): the original aryne moieties were expelled as a
moiety in the biphenyl thioether by-products.
The use of arynes to react with neutral nucleophiles
containing an N, S-, or O-atom to produce heterocyclic and
phenolic products offers the following three advantages. First,
the three reactions shown in Scheme 1 involve domino
processes, which require simple laboratory manipulations.
Second, isolation of the intermediates is no longer necessary
and purification procedures are simplified. Third, the desired
products are often generated in good-to-high yields under mild
conditions.
Analytical thin layer chromatography (TLC) was performed on
precoated plates (silica gel 60 F-254). Purification by gravity and dry
column chromatography was carried out by use of Silicycle ultra-
pure silica gel (particle size 40–63 μM, 230–400 mesh). HPLC
analysis was performed on high performance liquid chromatog-
raphy with UV detection monitored at 254 nm by use of Thermo
5 μm Hypersil ODS (250 mm×4.6 mm i.d.) column with acetonitrile
and water as the eluent.
Infrared spectra (IR) were measured on a Fourier transform infrared
spectrometer (FT-IR). Absorption intensities are recorded by the
following abbreviations: s, strong; m, medium; and w, weak. Proton
NMR spectra were obtained on 400 MHz and 600 MHz spectrom-
eters by use of chloroform-d (CDCl3) as the solvent. Proton NMR
chemical shifts were referenced to the residual protonated solvent
(δ 7.24 ppm for chloroform). Carbon-13 NMR spectra were obtained
on 100 MHz and 150 MHz spectrometers by use of chloroform-d
(CDCl3) as the solvents. Carbon-13 chemical shifts were referenced
to the center of the CDCl3 triplet (δ 77.0 ppm). Multiplicities are
recorded by the following abbreviations: s, singlet; d, doublet; dd,
doublet of doublet; t, triplet; q, quartet; m, multiplet; and J,
coupling constant (hertz). High-resolution mass spectra (HRMS)
were measured on an instrument by use of a time-of-flight mass
analyzer (TOF) with electrospray ionization (ESI).
Experimental Section
General Information: All reactions were carried out in oven-dried
°
glassware (120 C) under an atmosphere of nitrogen unless as
indicated otherwise. Dichloromethane, ethyl acetate, and hexanes
from Mallinckrodt Chemical Co. were dried and distilled from CaH2.
Tetrahydrofuran (THF) from Mallinckrodt Chemical Co. was dried by
distillation from sodium and benzophenone under an atmosphere
of nitrogen. The reagents purchased from Alfa Aesar included
Standard Procedure 1for the Single-Flask Synthesis of 1,2-
Dihydroquinolines. To a stirred solution of 2-silylphenyl triflates 1
(1.0 equiv) in dry THF (1.5–3.5 mL) was added Schiff bases 2
(1.1 equiv), alkynes 3 (1.2 equiv), and CsF (1.2 equiv) at room
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temperature under nitrogen atmosphere. After the reaction mixture
76% yield as a colorless oil: TLC Rf =0.35 (25% EtOAc in hexanes as
the eluent); 1H NMR (CDCl3, 400 MHz) δ 7.84 (d, J=7.2 Hz, 1 H, ArH),
7.42–7.30 (m, 4 H, 4×ArH), 7.10 (d, J=7.6 Hz, 2 H, 2×ArH), 7.00 (t,
J=7.2 Hz, 1 H, ArH), 6.80 (d, J=7.6 Hz, 2 H, 2×ArH), 6.66 (t, J=
7.2 Hz, 1 H, ArH), 6.61 (d, J=7.6 Hz, 2 H, 2×ArH), 5.28 (s, 1 H,
NCHAr), 3.84 (s, 3 H, ArOCH3), 3.78 (s, 3 H, CO2CH3), 3.62 (s, 3 H,
CO2CH3); 13C NMR (CDCl3, 100 MHz) δ 163.3 (C=O), 163.2 (C=O),
159.1, 144.9, 140.1, 138.1, 135.6, 130.3, 129.9, 128.8, 126.4, 124.3,
123.9, 121.8, 119.8, 118.2, 116.0, 113.5, 68.1 (NCHAr), 55.1 (ArOCH3),
52.3 (CO2CH3), 51.9 (CO2CH3); IR (neat) 2952 (w), 1732 (s, C=O), 1602
(m), 1509 (m), 1248 (m), 1171 (w), 1032 (w), 748 (w) cmÀ 1; HRMS
(ESI-TOF) m/z [M+H]+ calcd for C26H23NO5 +H 430.1654, found
430.1655.
1
2
3
4
5
6
7
8
9
°
was stirred at 40 C for 10–12 h, it was cooled to room temperature.
The reaction mixture was quenched with water (5.0 mL) and then
extracted with EtOAc (3×5.0 mL). The combined organic layers
were dried over MgSO4 (s), filtered, and concentrated under
reduced pressure to afford the products. It was then purified by use
of column chromatography on silica gel with EtOAc in hexanes as
the eluent to give the desired 1,2-dihydroquinolines 4.
Standard Procedure 2for the Single-Flask Synthesis of Epoxides.
To a stirred solution of 2-silylphenyl triflate 1a (1.0 equiv) in dry
acetonitrile (2.0–3.5 mL) was added thioether 7 (1.1 equiv), alde-
hydes/ketones 8, 13, or 15 (1.2 equiv), and CsF (1.2 equiv) at room
temperature under nitrogen atmosphere. After the reaction mixture
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
°
was stirred at 25 C for 4.0–6.0 h, it was quenched with water
3,4-Dimethoxycarbonyl-2-[(p-methoxycarbonyl)phenyl]-N-phenyl-
1,2-dihydroquinoline (4c). The Standard Procedure 1 was followed
by use of 2-silylphenyl triflate 1a (56.4 mg, 0.189 mmol, 1.0 equiv),
Schiff base 2c[37] (49.7 mg, 0.208 mmol, 1.1 equiv), DMAD (3a,
32.1 mg, 0.226 mmol, 1.2 equiv), and CsF (34.3 mg, 0.226 mmol,
1.2 equiv) in THF (1.5 mL). After the reaction mixture was stirred at
(5.0 mL) and then extracted with EtOAc (3×5.0 mL). The combined
organic layers were dried over MgSO4 (s), filtered, and concentrated
under reduced pressure to afford the products. It was then purified
by use of column chromatography on silica gel with EtOAc in
hexanes as the eluent to give the desired epoxides 9, 14, and 16.
°
40 C for 10 h, it was quenched and worked up. The residue was
Standard Procedure 3for the Single-Flask Synthesis of Phenolic
Ethers. To a stirred solution of 2-silylphenyl triflate 1 (1.0 equiv) in
dry THF (2.5–5.0 mL) was added allyl ethers 17 (2.0 equiv) and CsF
(1.2 equiv) at room temperature under nitrogen atmosphere. After
purified by use of column chromatography (8.0% EtOAc in hexanes
as the eluent) to give 1,2-dihydroquinoline 4c (70.9 mg,
0.155 mmol) in 82% yield as a yellow oil: TLC Rf =0.40 (25% EtOAc
1
in hexanes as the eluent); H NMR (CDCl3, 400 MHz) δ 8.05 (d, J=
°
the reaction mixture was stirred at 50 C for 24–30 h, it was cooled
7.6 Hz, 1 H, ArH), 7.94 (d, J=7.6 Hz, 1 H, ArH), 7.84–7.81 (m, 1 H,
ArH), 7.42–7.33 (m, 4 H, 4×ArH), 7.08 (d, J=7.6 Hz, 2 H, 2×ArH),
6.97 (t, J=7.2 Hz, 1 H, ArH), 6.77 (t, J=7.2 Hz, 1 H, ArH), 6.59 (d, J=
7.6 Hz, 2 H, 2×ArH), 5.37 (s, 1 H, NCHAr), 3.85 (s, 3 H, ArCO2CH3),
3.78 (s, 3 H, CO2CH3), 3.64 (s, 3 H, CO2CH3); 13C NMR (CDCl3,
100 MHz) δ 165.5 (C=O), 164.0 (C=O), 163.7 (C=O), 145.3, 143.9,
140.0, 136.2, 130.3, 130.0, 129.9, 128.8, 128.1, 126.6, 124.3, 123.8,
122.0, 119.0, 118.3, 116.2, 68.3 (NCHAr), 52.2 (ArCO2CH3), 51.3
(CO2CH3), 51.0 (CO2CH3); IR (neat) 2952 (w), 1735 (s, C=O), 1601 (w),
1505 (m), 1437 (w), 1249 (m), 1171 (w), 749 (w) cmÀ 1; HRMS (ESI-
TOF) m/z [M+H]+ calcd for C27H23NO6 +H 458.1603, found
458.1602.
to room temperature. The reaction mixture was quenched with
water (5.0 mL) and then extracted with EtOAc (3×5.0 mL). The
combined organic layers were dried over MgSO4 (s), filtered, and
concentrated under reduced pressure to afford the products. It was
then purified by use of column chromatography on silica gel with
EtOAc in hexanes as the eluent to give the desired phenolic ethers
18.
Experimental Procedures for the Syntheses of 1,2-Dihydroquino-
lines 4, Epoxides 9, 14, 16, and Phenolic Ethers 18:
3,4-Dimethoxycarbonyl-2-(p-methylphenyl)-N-phenyl-1,2-dihy-
droquinoline (4a). The Standard Procedure 1 was followed by use
of 2-silylphenyl triflate 1a (343 mg, 1.15 mmol, 1.0 equiv), Schiff
base 2a[36] (246 mg, 1.26 mmol, 1.1 equiv), DMAD (3a, 196 mg,
1.38 mmol, 1.2 equiv), and CsF (210 mg, 1.38 mmol, 1.2 equiv) in
3,4-Dimethoxycarbonyl-2,N-di(p-methylphenyl)-1,2-dihydroqui-
noline (4d). The Standard Procedure 1 was followed by use of 2-
silylphenyl triflate 1a (328 mg, 1.09 mmol, 1.0 equiv), Schiff base
2d[38] (252 mg, 1.21 mmol, 1.1 equiv), DMAD (3a, 187 mg,
1.31 mmol, 1.2 equiv), and CsF (201 mg, 1.31 mmol, 1.2 equiv) in
°
THF (3.5 mL). After the reaction mixture was stirred at 40 C for
10 h, it was quenched and worked up. The residue was purified by
use of column chromatography (10% EtOAc in hexanes as the
eluent) to give 1,2-dihydroquinoline 4a (371 mg, 0.892 mmol) in
78% yield as a yellow oil: TLC Rf =0.40 (25% EtOAc in hexanes as
the eluent); 1H NMR (CDCl3, 400 MHz) δ 7.84 (d, J=7.2 Hz, 1 H, ArH),
7.47–7.31 (m, 4 H, 4×ArH), 7.29–7.26 (m, 2 H, 2×ArH), 7.11 (d, J=
7.2 Hz, 2 H, 2×ArH), 6.97 (t, J=7.2 Hz, 1 H, ArH), 6.76 (t, J=7.2 Hz, 1
H, ArH), 6.60 (d, J=7.2 Hz, 2 H, 2×ArH), 5.20 (s, 1 H, NCHAr), 3.70 (s,
3 H, CO2CH3), 3.61 (s, 3 H, CO2CH3), 2.15 (s, 3 H, ArCH3); 13C NMR
(CDCl3, 100 MHz) δ 163.4 (C=O), 163.3 (C=O), 145.0, 140.1, 138.1,
136.0, 134.9, 130.0, 129.4, 128.2, 128.1, 126.5, 124.3, 123.1, 121.1,
119.1, 117.7, 115.8, 68.2 (NCHAr), 52.2 (CO2CH3), 51.9 (CO2CH3), 22.0
(ArCH3); IR (neat) 2952 (w), 1734 (s, C=O), 1508 (m), 1437 (w), 1249
(m), 1171 (w), 1032 (w), 749 (w) cmÀ 1; HRMS (ESI-TOF) m/z [M+
Na]+ calcd for C26H23NO4 +Na 436.1524, found 436.1526.
°
THF (3.5 mL). After the reaction mixture was stirred at 40 C for
12 h, it was quenched and worked up. The residue was purified by
use of column chromatography (10% EtOAc in hexanes as the
eluent) to give 1,2-dihydroquinoline 4d (362 mg, 0.847 mmol) in
77% yield as a colorless oil: TLC Rf =0.35 (25% EtOAc in hexanes as
the eluent); 1H NMR (CDCl3, 400 MHz) δ 7.87 (d, J=7.6 Hz, 1 H, ArH),
7.39–7.25 (m, 6 H, 6×ArH), 7.23–7.15 (m, 4 H, 4×ArH), 6.97 (t, J=
7.2 Hz, 1 H, ArH), 5.20 (s, 1 H, NCHAr), 3.75 (s, 3 H, CO2CH3), 3.65 (s, 3
H, CO2CH3), 2.16 (s, 3 H, ArCH3), 2.04 (s, 3 H, ArCH3); 13C NMR (CDCl3,
100 MHz) δ 163.8 (C=O), 163.0 (C=O), 145.3, 140.0, 138.4, 136.3,
135.0, 130.6, 130.1, 129.9, 129.3, 128.8, 126.7, 124.3, 123.2, 119.5,
118.2, 116.0, 68.1 (NCHAr), 52.5 (CO2CH3), 52.3 (CO2CH3), 21.5
(ArCH3), 20.7 (ArCH3); IR (neat) 2952 (w), 1735 (s, C=O), 1602 (w),
1504 (m), 1248 (m), 1171 (w), 1032 (w), 749 (w) cmÀ 1; HRMS (ESI-
TOF) m/z [M+H]+ calcd for C27H25NO4 +H 428.1861, found
428.1865.
3,4-Dimethoxycarbonyl-2-(p-methoxyphenyl)-N-phenyl-1,2-dihy-
droquinoline (4b). The Standard Procedure 1 was followed by use
of 2-silylphenyl triflate 1a (53.5 mg, 0.179 mmol, 1.0 equiv), Schiff
base 2b[36] (41.6 mg, 0.197 mmol, 1.1 equiv), DMAD (3a, 30.5 mg,
0.215 mmol, 1.2 equiv), and CsF (32.6 mg, 0.215 mmol, 1.2 equiv) in
3,4-Dimethoxycarbonyl-2-(p-methoxyphenyl)-N-(p-meth-
ylphenyl)-1,2-dihydroquinoline (4e). The Standard Procedure 1
was followed by use of 2-silylphenyl triflate 1a (55.1 mg,
0.184 mmol, 1.0 equiv), Schiff base 2e[39] (45.7 mg, 0.203 mmol,
1.1 equiv), DMAD (3a, 31.3 mg, 0.221 mmol, 1.2 equiv), and CsF
(35.5 mg, 0.221 mmol, 1.2 equiv) in THF (2.0 mL). After the reaction
°
THF (1.5 mL). After the reaction mixture was stirred at 40 C for
12 h, it was quenched and worked up. The residue was purified by
use of column chromatography (10⊥% EtOAc in hexanes as the
eluent) to give 1,2-dihydroquinoline 4b (58.1 mg, 0.136 mmol) in
°
mixture was stirred at 40 C for 12 h, it was quenched and worked
up. The residue was purified by use of column chromatography
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(8.0% EtOAc in hexanes as the eluent) to give 1,2-dihydroquinoline
residue was purified by use of column chromatography (10% EtOAc
in hexanes as the eluent) to give 1,2-dihydroquinoline 4h (359 mg,
0.785 mmol) in 78% yield as a yellow oil: TLC Rf =0.30 (25% EtOAc
1
2
3
4
5
6
7
8
9
4e (62.2 mg, 0.140 mmol) in 76% yield as a yellow oil: TLC Rf =0.45
1
(25% EtOAc in hexanes as the eluent); H NMR (CDCl3, 400 MHz) δ
1
7.85 (d, J=7.6 Hz, 1 H, ArH), 7.48 (d, J=7.6 Hz, 2 H, 2×ArH), 7.40–
7.23 (m, 6 H, 6×ArH), 7.00 (t, J=7.2 Hz, 1 H, ArH), 6.80 (d, J=7.6 Hz,
2 H, 2×ArH), 5.36 (s, 1 H, NCHAr), 3.82 (s, 3 H, ArOCH3), 3.69 (s, 3 H,
CO2CH3), 3.62 (s, 3 H, CO2CH3), 2.58 (s, 3 H, ArCH3); 13C NMR (CDCl3,
100 MHz) δ 164.6 (C=O), 163.8 (C=O), 158.9, 145.5, 140.0, 136.1,
135.4, 130.8, 130.1, 129.9, 128.9, 125.8, 124.6, 123.8, 119.3, 118.6,
116.6, 114.1, 68.4 (NCHAr), 55.4 (ArOCH3), 52.8 (CO2CH3), 52.2
(CO2CH3), 21.8 (ArCH3); IR (neat) 2953 (w), 1735 (s, C=O), 1601 (m),
1504 (m), 1249 (m), 1172 (m), 1032 (w), 749 (w) cmÀ 1; HRMS (ESI-
TOF) m/z [M+H]+ calcd for C27H25NO5 +H 444.1811, found
444.1813.
in hexanes as the eluent); H NMR (CDCl3, 400 MHz) δ 7.84 (d, J=
7.2 Hz, 1 H, ArH), 7.42–7.32 (m, 4 H, 4×ArH), 7.07 (d, J=7.6 Hz, 2 H,
2×ArH), 6.99 (t, J=7.2 Hz, 1 H, ArH), 6.78 (d, J=7.6 Hz, 2 H, 2×ArH),
6.68 (t, J=7.2 Hz, 1 H, ArH), 6.60 (d, J=7.6 Hz, 2 H, 2×ArH), 5.22 (s,
1 H, NCHAr), 4.20–4.13 (m, 2 H, CO2CH2), 4.09–4.02 (m, 2 H, CO2CH2),
3.84 (s, 3 H, ArOCH3), 1.28 (t, J=7.2 Hz, 3 H, CO2CH2CH3), 1.15 (t, J=
7.2 Hz, 3 H, CO2CH2CH3); 13C NMR (CDCl3, 100 MHz) δ 163.8 (C=O),
163.1 (C=O), 159.4, 144.6, 140.3, 137.7, 135.2, 130.0, 129.4, 128.8,
125.5, 124.3, 123.8, 121.8, 119.3, 118.2, 116.0, 114.1, 68.2 (NCHAr),
61.1 (CO2CH2), 60.0 (CO2CH2), 55.1 (ArOCH3), 14.0 (CH2CH3), 13.9
(CH2CH3); IR (neat) 2953 (w), 1731 (s, C=O), 1601 (m), 1505 (m), 1249
(m), 1171 (w), 1032 (w), 749 (w) cmÀ 1; HRMS (ESI-TOF) m/z [M+H]+
calcd for C28H27NO5 +H 458.1967, found 458.1965.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
N-(p-Chlorophenyl)-3,4-dimethoxycarbonyl-2-phenyl-1,2-dihydro-
quinoline (4f). The Standard Procedure 1 was followed by use of 2-
silylphenyl triflate 1a (342 mg, 1.14 mmol, 1.0 equiv), Schiff base
2g[40] (272 mg, 1.26 mmol, 1.1 equiv), DMAD (3a, 195 mg,
1.37 mmol, 1.2 equiv), and CsF (208 mg, 1.37 mmol, 1.2 equiv) in
3,4-Diethoxycarbonyl-2-[(p-methoxycarbonyl)phenyl]-N-phenyl-
1,2-dihydroquinoline (4i). The Standard Procedure 1 was followed
by use of 2-silylphenyl triflate 1a (54.3 mg, 0.182 mmol, 1.0 equiv),
Schiff base 2c (48.1 mg, 0.201 mmol, 1.1 equiv), diethyl acetylenedi-
carboxylate (3b, 37.1 mg, 0.218 mmol, 1.2 equiv), and CsF (33.1 mg,
0.218 mmol, 1.2 equiv) in THF (1.5 mL). After the reaction mixture
°
THF (3.5 mL). After the reaction mixture was stirred at 40 C for
10 h, it was quenched and worked up. The residue was purified by
use of column chromatography (8.0% EtOAc in hexanes as the
eluent) to give 1,2-dihydroquinoline 4f (398 mg, 0.917 mmol) in
80% yield as a yellow oil: TLC Rf =0.45 (25% EtOAc in hexanes as
the eluent); 1H NMR (CDCl3, 400 MHz) δ 7.84 (d, J=7.2 Hz, 1 H, ArH),
7.39-7.33 (m, 5 H, 5×ArH), 7.27 (d, J=7.6 Hz, 2 H, 2×ArH), 7.20–7.15
(m, 4 H, 4×ArH), 6.96 (t, J=7.2 Hz, 1 H, ArH), 5.28 (s, 1 H, NCHAr),
3.85 (s, 3 H, CO2CH3), 3.77 (s, 3 H, CO2CH3); 13C NMR (CDCl3,
150 MHz) δ 164.1 (C=O), 163.5 (C=O), 145.5, 141.2, 139.8, 135.9,
130.4,129.8, 128.8, 128.2, 127.2, 126.7, 126.4, 124.4, 123.9, 120.1,
118.1, 116.3, 68.6 (NCHAr), 52.4 (CO2CH3), 52.1 (CO2CH3); IR (neat)
2955 (w), 1733 (s, C=O), 1507 (m), 1357 (m), 1249 (m), 1171 (m),
1032 (m), 749 (w) cmÀ 1; HRMS (ESI-TOF) m/z [M+H]+ calcd for
C25H20ClNO4 +H 434.1159, found 434.1156.
°
was stirred at 40 C for 12 h, it was quenched and worked up. The
residue was purified by use of column chromatography (8.0%
EtOAc in hexanes as the eluent) to give 1,2-dihydroquinoline 4i
(75.1 mg, 0.154 mmol) in 85% yield as a yellow oil: TLC Rf =0.40
1
(25% EtOAc in hexanes as the eluent); H NMR (CDCl3, 400 MHz) δ
8.08 (d, J=7.6 Hz, 1 H, ArH), 8.00 (d, J=7.6 Hz, 1 H, ArH), 7.83 (d, J=
7.6 Hz, 1 H, ArH), 7.46–7.39 (m, 4 H, 4×ArH), 7.08 (d, J=7.6 Hz, 2 H,
2×ArH), 6.97 (t, J=7.2 Hz, 1 H, ArH), 6.62–6.55 (m, 3 H, 3×ArH),
5.41 (s, 1 H, NCHAr), 4.31–4.24 (m, 2 H, CO2CH2), 4.08–4.02 (m, 2 H,
CO2CH2), 3.83 (s, 3 H, CO2CH3), 1.29 (t, J=7.2 Hz, 3 H, CO2CH2CH3),
1.09 (t, J=7.2 Hz, 3 H, CO2CH2CH3); 13C NMR (CDCl3, 100 MHz) δ
165.4 (C=O), 164.1 (C=O), 163.2 (C=O), 144.6, 143.2, 140.1, 135.5,
130.1, 129.6, 128.6, 128.1, 127.9, 126.8, 124.4, 123.9, 121.8, 119.1,
118.0, 116.4, 68.9 (NCHAr), 61.1 (CO2CH2), 60.0 (CO2CH2), 52.2
(CO2CH3), 14.0 (CH2CH3), 13.9 (CH2CH3); IR (neat) 2953 (m), 1733 (s,
3,4-Diethoxycarbonyl-2-(p-methylphenyl)-N-phenyl-1,2-dihydro-
quinoline (4g). The Standard Procedure 1 was followed by use of
2-silylphenyl triflate 1a (55.3 mg, 0.185 mmol, 1.0 equiv), Schiff
base 2a (39.6 mg, 0.203 mmol, 1.1 equiv), diethyl acetylenedicar-
boxylate (3b, 37.8 mg, 0.222 mmol, 1.2 equiv), and CsF (33.7 mg,
0.222 mmol, 1.2 equiv) in THF (2.0 mL). After the reaction mixture
C=O), 1612 (m), 1509 (m), 1437 (w), 1249 (s), 1031 (w), 749 (w) cmÀ 1
;
HRMS (ESI-TOF) m/z [M+H]+ calcd for C29H27NO6 +H 486.1916,
found 486.1915.
°
was stirred at 40 C for 12 h, it was quenched and worked up. The
3,4-Diethoxycarbonyl-2,N-di(p-methoxyphenyl)-1,2-dihydroqui-
noline (4j). The Standard Procedure 1 was followed by use of 2-
silylphenyl triflate 1a (52.2 mg, 0.175 mmol, 1.0 equiv), Schiff base
2f[38] (45.6 mg, 0.192 mmol, 1.1 equiv), diethyl acetylenedicarbox-
ylate (3b, 35.9 mg, 0.210 mmol, 1.2 equiv), and CsF (31.8 mg,
0.210 mmol, 1.2 equiv) in THF (1.5 mL). After the reaction mixture
residue was purified by use of column chromatography (8.0%
EtOAc in hexanes as the eluent) to give 1,2-dihydroquinoline 4g
(65.6 mg, 0.148 mmol) in 80% yield as a colorless oil: TLC Rf =0.45
1
(25% EtOAc in hexanes as the eluent); H NMR (CDCl3, 400 MHz) δ
7.84 (d, J=7.2 Hz, 1 H, ArH), 7.47–7.41 (m, 4 H, 4×ArH), 7.39–7.32
(m, 2 H, 2×ArH), 7.17 (d, J=7.6 Hz, 2 H, 2×ArH), 7.03 (t, J=7.2 Hz, 1
H, ArH), 6.76 (t, J=7.2 Hz, 1 H, ArH), 6.61 (d, J=7.6 Hz, 2 H, 2×ArH),
5.22 (s, 1 H, NCHAr), 4.25–4.21 (m, 2 H, CO2CH2), 4.17–4.13 (m, 2 H,
CO2CH2), 2.18 (s, 3 H, ArCH3), 1.15 (t, J=7.2 Hz, 3 H, CO2CH2CH3),
1.11 (t, J=7.2 Hz, 3 H, CO2CH2CH3); 13C NMR (CDCl3, 100 MHz) δ
163.5 (C=O), 163.3 (C=O), 145.0, 140.1, 138.2, 136.4, 135.0, 130.1,
129.9, 129.3, 128.8, 126.7, 124.3, 123.9, 120.9, 119.9, 118.1, 116.1,
68.2 (NCHAr), 61.2 (CO2CH2), 61.3 (CO2CH2), 21.9 (ArCH3), 14.4
(CH2CH3), 14.3 (CH2CH3); IR (neat) 2952 (w), 1733 (s, C=O), 1602 (w),
1507 (m), 1249 (m), 1171 (w), 1031 (w), 749 (w) cmÀ 1; HRMS (ESI-
TOF) m/z [M+H]+ calcd for C28H27NO4 +H 422.2018, found
442.2014.
°
was stirred at 40 C for 10 h, it was quenched and worked up. The
residue was purified by use of column chromatography (10% EtOAc
in hexanes as the eluent) to give 1,2-dihydroquinoline 4j (63.9 mg,
0.131 mmol) in 75% yield as a yellow oil: TLC Rf =0.30 (25% EtOAc
1
in hexanes as the eluent); H NMR (CDCl3, 600 MHz) δ 7.84 (d, J=
7.2 Hz, 1 H, ArH), 7.42-7.35 (m, 4 H, 4×ArH), 7.22 (d, J=7.8 Hz, 2 H,
2×ArH), 7.10 (t, J=7.2 Hz, 2 H, 2×ArH), 6.78 (d, J=7.2 Hz, 1 H, ArH),
6.64 (d, J=7.8 Hz, 2 H, 2×ArH), 5.22 (s, 1 H, NCHAr), 4.28–4.24 (m, 2
H, CO2CH2), 4.15–4.12 (m, 2 H, CO2CH2), 3.82 (s, 3 H, ArOCH3), 3.70 (s,
3 H, ArOCH3), 1.30 (t, J=7.2 Hz, 3 H, CO2CH2CH3), 1.15 (t, J=7.2 Hz,
3 H, CO2CH2CH3); 13C NMR (CDCl3, 150 MHz) δ 163.5 (C=O), 162.9
(C=O), 159.2, 159.0, 144.0, 142.2, 138.1, 135.1, 129.7, 128.0, 126.2,
124.5, 123.0, 120.0, 118.0, 116.0, 113.9, 112.3, 68.1 (NCHAr), 61.5
(CO2CH2), 61.2 (CO2CH2), 55.3 (ArOCH3), 55.2 (ArOCH3), 14.1 (CH2CH3),
14.0 (CH2CH3); IR (neat) 2955 (m), 1738 (s, C=O), 1505 (m), 1370 (m),
1248 (s), 1172 (m), 1033 (m), 749 (m) cmÀ 1; HRMS (ESI-TOF) m/z [M
+H]+ calcd for C29H29NO6 +H 488.2073, found 488.2066.
3,4-Diethoxycarbonyl-2-(p-methoxyphenyl)-N-phenyl-1,2-dihy-
droquinoline (4h). The Standard Procedure 1 was followed by use
of 2-silylphenyl triflate 1a (301 mg, 1.01 mmol, 1.0 equiv), Schiff
base 2b (234 mg, 1.11 mmol, 1.1 equiv), diethyl acetylenedicarbox-
ylate (3b, 205 mg, 1.21 mmol, 1.2 equiv), and CsF (183 mg,
1.21 mmol, 1.2 equiv) in THF (3.5 mL). After the reaction mixture
3,4-Dimethoxycarbonyl-6,7-dimethyl-2-(p-methoxyphenyl)-N-
phenyl-1,2-dihydroquinoline (4k). The Standard Procedure 1 was
°
was stirred at 40 C for 11 h, it was quenched and worked up. The
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followed by use of 2-silylphenyl triflate 1b (53.5 mg, 0.179 mmol,
1.0 equiv), Schiff base 2b (41.6 mg, 0.197 mmol, 1.1 equiv), DMAD
(3a, 30.5 mg, 0.215 mmol, 1.2 equiv), and CsF (32.6 mg,
0.215 mmol, 1.2 equiv) in THF (1.5 mL). After the reaction mixture
1.2 equiv), and CsF (42.9 mg, 0.286 mmol, 1.2 equiv) in acetonitrile
1
2
3
4
5
6
7
8
9
°
(2.0 mL). After the reaction mixture was stirred at 25 C for 6.0 h, it
was quenched and worked up. The residue was purified by use of
column chromatography (5.0% EtOAc in hexanes as the eluent) to
give trans-epoxide 9b (30.8 mg, 0.144 mmol) in 61% and cis-
epoxide 9b (6.51 mg, 0.031 mmol) in 13% yield as colorless oil: TLC
Rf =0.45 for trans-9b and Rf =0.46 for cis-9b (5.0⊥% EtOAc in
°
was stirred at 40 C for 10 h, it was quenched and worked up. The
residue was purified by use of column chromatography (8.0%
EtOAc in hexanes as the eluent) to give 1,2-dihydroquinoline 4k
(61.5 mg, 0.134 mmol) in 75% yield as a colorless oil: TLC Rf =0.45
1
hexanes as the eluent); H NMR (CDCl3, 400 MHz) trans-epoxide 9b:
1
(25% EtOAc in hexanes as the eluent); H NMR (CDCl3, 400 MHz) δ
δ 7.42–7.22 (m, 9 H, 9×ArH), 4.21 (d, J=2.0 Hz, 1 H, CHArF), 3.81 (d,
J=2.0 Hz, 1 H, CHPh); for cis-epoxide 9b: δ 7.42–7.22 (m, 9 H, 10×
ArH), 4.26 (d, J=4.0 Hz, 1 H, CHArF), 3.81 (d, J=4.0 Hz, 1 H, CHPh).
These spectroscopic data are in accordance with the literature
values.[43]
7.43 (d, J=7.6 Hz, 2 H, 2×ArH), 7.17–7.13 (m, 3 H, 3×ArH), 7.05 (s, 1
H, ArH), 6.83 (d, J=7.6 Hz, 2 H, 2×ArH), 6.74 (t, J=7.2 Hz, 1 H, ArH),
6.61 (d, J=7.2 Hz, 2 H, 2×ArH), 5.30 (s, 1 H, NCHAr), 3.83 (s, 3 H,
ArOCH3), 3.72 (s, 3 H, CO2CH3), 3.65 (s, 3 H, CO2CH3), 2.30 (s, 3 H,
ArCH3), 2.10 (s, 3 H, ArCH3); 13C NMR (CDCl3, 100 MHz) δ 165.2
(C=O), 163.4 (C=O), 158.2, 145.5, 138.1, 135.9, 135.3, 135.1,
130.2,129.8, 127.5, 126.2, 125.8, 121.9, 120.8, 119.8, 118.7, 114.5,
68.6 (NCHAr), 55.5 (ArOCH3), 52.5 (CO2CH3), 52.3 (CO2CH3), 19.8
(ArCH3), 18.8 (ArCH3); IR (neat) 2953 (m), 1732 (s, C=O), 1601 (m),
1507 (m), 1248 (m), 1171 (m), 1031 (m), 749 (w) cmÀ 1; HRMS (ESI-
TOF) m/z [M+H]+ calcd for C28H27NO5 +H 458.1967, found
458.1965.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
trans-2-(2-Chlorophenyl)-3-phenyloxirane (9c). The Standard Pro-
cedure 2 was followed by use of 2-silylphenyl triflate 1a (108 mg,
0.362 mmol, 1.0 equiv), thioether 7a (79.7 mg, 0.398 mmol,
1.1 equiv), 2-chlorobenzaldehyde (8c, 61.3 mg, 0.438 mmol,
1.2 equiv), and CsF (67.1 mg, 0.441 mmol, 1.2 equiv) in acetonitrile
°
(2.0 mL). After the reaction mixture was stirred at 25 C for 5.0 h, it
was quenched and worked up. The residue was purified by use of
column chromatography (5.0% EtOAc in hexanes as the eluent) to
give trans-epoxide 9c (58.5 mg, 0.253 mmol) in 70% yield as a
colorless oil: TLC Rf =0.35 (5.0% EtOAc in hexanes as the eluent); 1H
NMR (CDCl3, 400 MHz) δ 7.42–7.22 (m, 9 H, 9×ArH), 4.24 (d, J=
6,7-Dimethoxy-3,4-dimethoxycarbonyl-2-(p-methylphenyl)-N-
phenyl-1,2-dihydroquinoline (4l). The Standard Procedure 1 was
followed by use of 2-silylphenyl triflate 1c (54.7 mg, 0.183 mmol,
1.0 equiv), Schiff base 2a (39.3 mg, 0.201 mmol, 1.1 equiv), diethyl
acetylenedicarboxylate (3b, 37.2 mg, 0.219 mmol, 1.2 equiv), and
CsF (33.2 mg, 0.219 mmol, 1.2 equiv) in THF (1.5 mL). After the
2.0 Hz,
1 H, CHArCl), 3.76 (d, J=2.0 Hz, 1 H, CHPh). These
spectroscopic data are in accordance with the literature values.[44]
trans-2-(3-Bromo-4-fluorophenyl)-3-phenyloxirane (9d). The
°
reaction mixture was stirred at 40 C for 10 h, it was quenched and
Standard Procedure 2 was followed by use of 2-silylphenyl triflate
1a (326 mg, 1.09 mmol, 1.0 equiv), thioether 7a (240 mg,
1.20 mmol, 1.1 equiv), 3-bromo-4-fluorobenzaldehyde (8d, 265 mg,
1.30 mmol, 1.2 equiv), and CsF (203 mg, 1.34 mmol, 1.2 equiv) in
worked up. The residue was purified by use of column chromatog-
raphy (12% EtOAc in hexanes as the eluent) to give 1,2-
dihydroquinoline 4l (69.8 mg, 0.139 mmol) in 76% yield as a
1
colorless oil: TLC Rf =0.30 (25% EtOAc in hexanes as the eluent); H
°
acetonitrile (3.5 mL). After the reaction mixture was stirred at 25 C
NMR (CDCl3, 400 MHz) δ 7.35 (d, J=7.6 Hz, 2 H, 2×ArH), 7.27–7.23
(m, 2 H, 2×ArH), 7.18 (d, J=7.6 Hz, 2 H, 2×ArH), 6.80 (s, 1 H, ArH),
6.73 (s, 1 H, ArH), 6.67 (t, J=7.4 Hz, 1 H, ArH), 6.60 (d, J=7.4 Hz, 2 H,
2×ArH), 5.29 (s, 1 H, NCHAr), 4.29–4.27 (m, 2 H, CO2CH2), 4.18–4.16
(m, 2 H, CO2CH2), 3.83 (s, 3 H, ArOCH3), 3.72 (s, 3 H, ArOCH3), 2.34 (s,
3 H, ArCH3), 1.30 (t, J=7.2 Hz, 3 H, CO2CH2CH3), 1.17 (t, J=7.2 Hz, 3
H, CO2CH2CH3); 13C NMR (CDCl3, 100 MHz) δ 164.6 (C=O), 163.3
(C=O), 152.2, 149.8, 145.0, 140.0, 136.4, 135.5, 133.9, 130.3, 129.8,
128.7, 126.6, 121.2, 119.7, 117.9, 111.4, 110.1, 68.2 (NCHAr), 61.9
(CO2CH2), 61.4 (CO2CH2), 55.7 (ArOCH3), 55.3 (ArOCH3), 21.3 (ArCH3),
14.3 (CH2CH3), 13.9 (CH2CH3); IR (neat) 2952 (m), 1733 (s, C=O), 1602
(m), 1510 (m), 1248 (m), 1171 (m), 1032 (m), 748 (w) cmÀ 1; HRMS
(ESI-TOF) m/z [M+H]+ calcd for C30H31NO6 +H 502.2229, found
502.2228.
for 4.0 h, it was quenched and worked up. The residue was purified
by use of column chromatography (10% EtOAc in hexanes as the
eluent) to give trans-epoxide 9d (230 mg, 0.785 mmol) in 72% yield
as yellow solids: TLC Rf =0.35 (7.0% EtOAc in hexanes as the
eluent); mp (recrystallized from EtOH) 149.4–151.6 C; 1H NMR
°
(CDCl3, 400 MHz) δ 7.44–7.24 (m, 6 H, 6×ArH), 6.96 (d, J=6.8 Hz, 2
H, 2×ArH), 4.09 (s, 1 H, CHArBrF), 3.99 (s, 1 H, CHPh); 13C NMR
(CDCl3, 100 MHz) δ 160.4 (d, JCF =234), 137.4, 135.2, 132.1 (d, JCF
=
4.7), 128.8, 128.2, 125.6, 124.3 (d, JCF =6.4), 117.3 (d, JCF =22.8),
110.6 (d, JCF =22.6), 64.4 (CAr), 63.9 (CPh); IR (neat) 2955 (m), 1594
(s), 1502 (m), 1251 (s), 1180 (m), 1118 (m), 1033 (m), 749 (w) cmÀ 1
;
HRMS (ESI-TOF) m/z [M+H]+ calcd for C14H10BrFO+H 292.9977,
found 292.9975.
trans-2-(3-Bromo-4-methoxyphenyl)-3-phenyloxirane (9e). The
Standard Procedure 2 was followed by use of 2-silylphenyl triflate
1a (342 mg, 1.15 mmol, 1.0 equiv), thioether 7a (252 mg,
1.26 mmol, 1.1 equiv), 3-bromo-4-methoxybenzaldehyde (8e,
296 mg, 1.38 mmol, 1.2 equiv), and CsF (218 mg, 1.44 mmol,
1.2 equiv) in acetonitrile (3.5 mL). After the reaction mixture was
1,2-Diphenyloxirane (9a). The Standard Procedure 2 was followed
by use of 2-silylphenyl triflate 1a (152 mg, 0.511 mmol, 1.0 equiv),
thioether 7a[41] (112 mg, 0.562 mmol, 1.1 equiv), benzaldehyde (8a,
65.1 mg, 0.613 mmol, 1.2 equiv), and CsF (93.5 mg, 0.615 mmol,
1.2 equiv) in acetonitrile (2.5 mL). After the reaction mixture was
°
stirred at 25 C for 6.0 h, it was quenched and worked up. The
°
stirred at 25 C for 4.0 h, it was quenched and worked up. The
residue was purified by use of column chromatography (10% EtOAc
in hexanes as the eluent) to give trans-epoxide 9a (41.9 mg,
0.214 mmol) in 42% and cis-epoxide 9a (18.0 mg, 0.091 mmol) in
18% yield as colorless oil: TLC Rf =0.34 for trans-epoxide 9a and
Rf =0.35 for cis-epoxide 9a (5.0% EtOAc in hexanes as the eluent);
1H NMR (CDCl3, 400 MHz) for trans-epoxide 9a: δ 7.48–7.28 (m, 10
H, 10×ArH), 3.88 (s, 2 H, 2×CHPh); for cis-epoxide 9a: δ 7.18–7.09
(m, 10 H, 10×ArH), 4.36 (s, 2 H, 2×CHPh). These spectroscopic data
are in accordance with the literature values.[42]
residue was purified by use of column chromatography (10% EtOAc
in hexanes as the eluent) to give trans-epoxide 9e (237 mg,
0.779 mmol) in 68% yield as yellow solids: TLC Rf =0.30 (7.0%
EtOAc in hexanes as the eluent); mp (recrystallized from EtOH)
1
°
156.8–158.4 C; H NMR (CDCl3, 400 MHz) δ 7.52 (s, 1 H, ArH), 7.40–
7.25 (m, 6 H, 6×ArH), 6.90 (d, J=8.4 Hz, 1 H, ArH), 3.91 (s, 3 H,
ArOCH3), 3.82 (s, 1 H, CHArBr), 3.79 (s, 1 H, CHPh); 13C NMR (CDCl3,
100 MHz) δ 155.9, 136.7, 130.6, 130.3, 128.5, 128.3, 126.8, 125.8,
111.9, 111.7, 62.7 (CAr), 61.8 (CPh), 56.3 (OCH3); IR (neat) 2927 (m),
1597 (m), 1505 (m), 1252 (s), 1180 (m), 1115 (m), 1034 (w), 749 (w)
2-(2-Fluorophenyl)-3-phenyloxirane (9b). The Standard Procedure
2
was followed by use of 2-silylphenyl triflate 1a (110 mg,
cmÀ 1
;
HRMS (ESI-TOF) m/z [M+H]+ calcd for C15H13BrO2 +H
0.236 mmol, 1.0 equiv), thioether 7a (52.1 mg, 0.259 mmol,
1.1 equiv), 2-fluorobenzaldehyde (8b, 35.1 mg, 0.283 mmol,
305.0177, found 305.0175.
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trans-2-(2-Nitrophenyl)-3-phenyloxirane (9f). The Standard Proce-
1.0 equiv), thioether 7a (237 mg, 1.19 mmol, 1.1 equiv), cyclopenta-
none (13a, 109 mg, 1.29 mmol, 1.2 equiv), and CsF (201 mg,
1.31 mmol, 1.2 equiv) in acetonitrile (3.5 mL). After the reaction
1
2
3
4
5
6
7
8
9
dure 2 was followed by use of 2-silylphenyl triflate 1a (102 mg,
0.341 mmol, 1.0 equiv), thioether 7a (75.3 mg, 0.376 mmol,
1.1 equiv), 2-nitrobenzaldehyde (8f, 62.8 mg, 0.416 mmol,
1.2 equiv), and CsF (66.3 mg, 0.436 mmol, 1.2 equiv) in acetonitrile
°
mixture was stirred at 25 C for 6.0 h, it was quenched and worked
up. The residue was purified by use of column chromatography
(5.0% EtOAc in hexanes as the eluent) to give epoxide 14a
(112 mg, 0.648 mmol) in 65% yield as a yellow oil: TLC Rf =0.45
°
(2.5 mL). After the reaction mixture was stirred at 25 C for 4.0 h, it
was quenched and worked up. The residue was purified by use of
column chromatography (5.0% EtOAc in hexanes as the eluent) to
give trans-epoxide 9f (70.6 mg, 0.293 mmol) in 78% yield as yellow
1
(5.0% EtOAc in hexanes as the eluent); H NMR (CDCl3, 400 MHz) δ
7.39–7.33 (m, 2 H, 2×ArH), 7.29–7.23 (m, 3 H, 3×ArH), 4.02 (s, 1 H,
CHPh), 2.10–1.96 (m, 2 H, CH2), 1.89–1.73 (m, 2 H, CH2), 1.69–1.52
(m, 4 H, 2×CH2). These spectroscopic data are in accordance with
the literature values.[50]
1
solids: TLC Rf =0.30 (5.0% EtOAc in hexanes as the eluent); H NMR
(CDCl3, 400 MHz) δ 8.15 (d, J=7.6 Hz, 1 H, ArH), 7.72 (d, J=7.2 Hz, 2
H, 2×ArH), 7.49 (t, J=6.4 Hz, 1 H, ArH), 7.38–7.28 (m, 5 H, 5×ArH),
4.49 (s, 1 H, CHArNO2), 3.77 (s, 1 H, CHPh). These spectroscopic data
are in accordance with the literature values.[45]
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
2-Phenyl-1-oxaspiro[2.5]octane (14b). The Standard Procedure 2
was followed by use of 2-silylphenyl triflate 1a (105 mg,
0.351 mmol, 1.0 equiv), thioether 7a (78.9 mg, 0.394 mmol,
1.1 equiv), cyclohexanone (13b, 43.4 mg, 0.442 mmol, 1.2 equiv),
and CsF (68.2 mg, 0.449 mmol, 1.2 equiv) in acetonitrile (2.0 mL).
trans-2-(3-Nitrophenyl)-3-phenyloxirane (9g). The Standard Proce-
dure 2 was followed by use of 2-silylphenyl triflate 1a (105 mg,
0.351 mmol, 1.0 equiv), thioether 7a (77.6 mg, 0.387 mmol,
1.1 equiv), 3-nitrobenzaldehyde (8g, 63.6 mg, 0.421 mmol,
1.2 equiv), and CsF (63.9 mg, 0.421 mmol, 1.2 equiv) in acetonitrile
°
After the reaction mixture was stirred at 25 C for 6.0 h, it was
quenched and worked up. The residue was purified by use of
column chromatography (5.0% EtOAc in hexanes as the eluent) to
give epoxide 14b (46.2 mg, 0.245 mmol) in 70% yield as a yellow
°
(2.5 mL). After the reaction mixture was stirred at 25 C for 4.0 h, it
was quenched and worked up. The residue was purified by use of
column chromatography (5.0% EtOAc in hexanes as the eluent) to
give trans-epoxide 9g (63.4 mg, 0.263 mmol) in 75% yield as a
colorless oil: TLC Rf =0.30 (5.0% EtOAc in hexanes as the eluent); 1H
NMR (CDCl3, 400 MHz) δ 8.20–8.17 (m, 2 H, 2×ArH), 7.67–7.32 (m, 7
H, 7×ArH), 3.96 (d, J=1.6 Hz, 1 H, CHArNO2), 3.86 (d, J=1.6 Hz, 1 H,
CHPh). These spectroscopic data are in accordance with the
literature values.[46]
1
oil: TLC Rf =0.40 (5.0 % EtOAc in hexanes as the eluent); H NMR
(CDCl3, 400 MHz) δ 7.32–7.25 (m, 2 H, 2×ArH), 7.22–7.18 (m, 3 H, 3×
ArH), 3.78 (s, 1 H, CHPh), 1.78–1.25 (m, 10 H, 5×CH2). These
spectroscopic data are in accordance with the literature values.[51]
Diethyl 3-(phenyl)oxirane-2,2-dicarboxylate (16). The Standard
Procedure 2 was followed by use of 2-silylphenyl triflate 1a
(55.5 mg, 0.186 mmol, 1.0 equiv), thioether 7a (41.2 mg,
0.205 mmol, 1.1 equiv), diethyl oxomalonate (15, 38.8 mg,
0.223 mmol, 1.2 equiv), and CsF (34.2 mg, 0.225 mmol, 1.2 equiv) in
trans-2-(4-Methoxycarbonyl)phenyl-(3-methoxy)phenyloxirane
(9h). The Standard Procedure 2 was followed by use of 2-
silylphenyl triflate 1a (52.1 mg, 0.174 mmol, 1.0 equiv), thioether
7b[47] (44.1 mg, 0.191 mmol, 1.1 equiv), methyl 4-formylbenzoate
(8h, 34.3 mg, 0.208 mmol, 1.2 equiv), and CsF (31.7 mg,
0.209 mmol, 1.2 equiv) in acetonitrile (2.0 mL). After the reaction
°
acetonitrile (2.0 mL). After the reaction mixture was stirred at 25 C
for 4.0 h, it was quenched and worked up. The residue was purified
by use of column chromatography (5.0% EtOAc in hexanes as the
eluent) to give epoxide 16 (39.3 mg, 0.148 mmol) in 80% yield as a
colorless oil: TLC Rf =0.40 (5.0% EtOAc in hexanes as the eluent); 1H
NMR (CDCl3, 400 MHz) δ 7.32–7.28 (m, 2 H, 2×ArH), 7.25–7.19 (m, 3
H, 3×ArH), 4.54 (s, 1 H, CHPh), 4.33–4.28 (m, 2 H, OCH2), 4.04–3.98
(m, 2 H, OCH2), 1.31 (t, J=7.2 Hz, CH3), 0.94 (t, J=7.2 Hz, CH3). These
spectroscopic data are in accordance with the literature values.[52]
°
mixture was stirred at 25 C for 4.0 h, it was quenched and worked
up. The residue was purified by use of column chromatography
(8.0% EtOAc in hexanes as the eluent) to give trans-epoxide 9h
(39.5 mg, 0.139 mmol) in 80% yield as a yellow oil: TLC Rf =0.40
1
(10⊥% EtOAc in hexanes as the eluent); H NMR (CDCl3, 400 MHz) δ
8.00 (d, J=8.0 Hz, 2 H, 2×ArH), 7.31 (d, J=8.0 Hz, 2 H, 2×ArH), 7.20
(d, J=7.6 Hz, 2 H, 2×ArH), 6.88 (d, J=7.6 Hz, 2 H, 2×ArH), 4.09 (d,
J=1.6 Hz, 1 H, CHAr), 3.89 (s, 3 H, ArOCH3), 3.80 (s, 3 H, CO2CH3),
3.75 (d, J=1.6 Hz, 1 H, CHAr); 13C NMR (CDCl3, 100 MHz) δ 164.3
(C=O), 159.8, 141.9, 130.1, 129.7, 129.6, 125.8, 125.6, 114.3, 64.3
(CAr), 61.1 (CAr), 55.0 (ArOCH3), 51.5 (CO2CH3); IR (neat) 2953 (m),
1732 (s, C=O), 1597 (m), 1496 (m), 1252 (s), 1180 (s), 1032 (m), 752
(m) cmÀ 1; HRMS (ESI-TOF) m/z [M+H]+ calcd for C17H16O4 +H
285.1126, found 285.1128.
1-Allyl-2-methoxybenzene (18a). The Standard Procedure 3 was
followed by use of 2-silylphenyl triflate 1a (302 mg, 1.01 mmol,
1.0 equiv), 3-methoxy-1-propene (17a, 146 mg, 2.02 mmol,
2.0 equiv), and CsF (184 mg, 1.21 mmol, 1.2 equiv) in THF (3.5 mL).
°
After the reaction mixture was stirred at 50 C for 26 h, it was
quenched and worked up. The residue was purified by use of
column chromatography (3.0% EtOAc in hexanes as the eluent) to
give phenolic ether 18a (106 mg, 0.716 mmol) in 71% yield as a
colorless oil: TLC Rf =0.45 (5.0% EtOAc in hexanes as the eluent); 1H
NMR (CDCl3, 400 MHz) δ 7.26 (d, J=7.2 Hz, 1 H, ArH), 7.15 (d, J=
7.2 Hz, 1 H, ArH), 6.95–6.88 (m, 2 H, 2×ArH), 6.04–5.97 (m, 1 H,
HC=C), 5.07–5.03 (m, 2 H, C=CH2), 3.84 (s, 3 H, OCH3), 3.42 (d, J=
6.8 Hz, 2 H, ArCH2). These spectroscopic data are in accordance with
the literature values.[33]
trans-2,3-Di(4-methoxycarbonyl)phenyloxirane (9i). The Standard
Procedure 2 was followed by use of 2-silylphenyl triflate 1a
(151 mg, 0.506 mmol, 1.0 equiv), thioether 7c[48] (143 mg,
0.556 mmol, 1.1 equiv), methyl 4-formylbenzoate (8h, 99.5 mg,
0.607 mmol, 1.2 equiv), and CsF (99.1 mg, 0.652 mmol, 1.2 equiv) in
°
acetonitrile (3.0 mL). After the reaction mixture was stirred at 25 C
2-Allyl-1-phenoxybenzene (18b). The Standard Procedure 3 was
followed by use of 2-silylphenyl triflate 1a (82.4 mg, 0.276 mmol,
1.0 equiv), (allyloxy)benzene (17b, 74.2 mg, 0.552 mmol, 2.0 equiv),
and CsF (50.3 mg, 0.331 mmol, 1.2 equiv) in THF (2.5 mL). After the
for 6.0 h, it was quenched and worked up. The residue was purified
by use of column chromatography (10% EtOAc in hexanes as the
eluent) to give trans-epoxide 9i (102 mg, 0.329 mmol) in 65% yield
as a yellow oil: TLC Rf =0.30 (10% EtOAc in hexanes as the eluent);
1H NMR (CDCl3, 400 MHz) δ 8.02 (d, J=8.0 Hz, 4 H, 4×ArH), 7.33 (d,
J=8.0 Hz, 4 H, 4×ArH), 4.10 (s, 2 H, 2×CHAr), 3.95 (s, 6 H, 2×
CO2CH3). These spectroscopic data are in accordance with the
literature values.[49]
°
reaction mixture was stirred at 50 C for 30 h, it was quenched and
worked up. The residue was purified by use of column chromatog-
raphy (5.0% EtOAc in hexanes as the eluent) to give phenolic ether
18b (29.5 mg, 0.140 mmol) in 51% yield as a colorless oil: TLC Rf =
0.50 (10% EtOAc in hexanes as the eluent); 1H NMR (CDCl3,
400 MHz) δ 7.38 (d, J=7.6 Hz, 2 H, 2×ArH), 7.30 (d, J=7.2 Hz, 1 H,
ArH), 7.14–7.05 (m, 3 H, 3×ArH), 7.02 (t, J=7.2 Hz, 1 H, ArH), 6.98–
2-Phenyl-1-oxaspiro[2.4]heptane (14a). The Standard Procedure 2
was followed by use of 2-silylphenyl triflate 1a (324 mg, 1.08 mmol,
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6.93 (m, 2 H, 2×ArH), 6.03–5.98 (m, 1 H, HC=C), 5.13–5.11 (m, 2 H,
Standard Procedure 3 was followed by use of 2-silylphenyl triflate
1a (206 mg, 0.691 mmol, 1.0 equiv), allyl cholesteryl ether[55] (17d,
533 mg, 1.38 mmol, 2.0 equiv), and CsF (126 mg, 0.828 mmol,
1.2 equiv) in THF (5.0 mL). After the reaction mixture was stirred at
1
2
3
4
5
6
7
8
9
C=CH2), 3.43 (d, J=6.4 Hz, 2 H, ArCH2). These spectroscopic data are
in accordance with the literature values.[33]
2-(2-Methoxybenzyl)acrylic acid methyl ester (18c). The Standard
Procedure 3 was followed by use of 2-silylphenyl triflate 1a
(121 mg, 0.406 mmol, 1.0 equiv), methyl 2-(methoxymethyl)
acrylate[53] (17c, 73.2 mg, 0.812 mmol, 2.0 equiv), and CsF (92.2 mg,
0.486 mmol, 1.2 equiv) in THF (2.5 mL). After the reaction mixture
°
50 C for 30 h, it was quenched and worked up. The residue was
purified by use of column chromatography (10% EtOAc in hexanes
as the eluent) to give phenolic ether 18g (180 mg, 0.357 mmol) in
52% yield as white solids: TLC Rf =0.45 (10% EtOAc in hexanes as
1
°
the eluent); mp (recrystallized from EtOH) 126.6–128.2 C; H NMR
°
was stirred at 50 C for 24 h, it was quenched and worked up. The
(CDCl3, 400 MHz) δ 7.27 (d, J=7.2 Hz, 1 H, ArH), 7.16 (d, J=7.2 Hz, 1
H, ArH), 6.96–6.87 (m, 2 H, 2×ArH), 6.96–6.87 (m, 1 H, HC=C), 5.33
(d, J=5.2 Hz, 1 H, MeCC=CH), 5.09–5.03 (m, 2 H, C=CH2), 4.09–4.01
(m, 1 H, ArOCH), 3.41 (d, J=6.8 Hz, 2 H, ArCH2), 2.50–2.46 (m, 1 H),
2.41–2.36 (m, 1 H), 2.03–1.97 (m, 3 H), 1.89–1.73 (m, 4 H), 1.57–1.42
(m, 6 H), 1.38–1.31 (m, 3 H), 1.28–1.24 (m, 2 H), 1.18–1.09 (m, 8 H),
1.02 (s, 3 H, CH3), 0.93 (d, J=6.4 Hz, 3 H, CH3), 0.87 (d, J=6.4 Hz, 6
H, C(CH3)2), 0.69 (s, 3 H, CH3); 13C NMR (CDCl3, 100 MHz) δ 157.6,
140.7, 137.2, 132.2, 129.8, 126.7,121.1, 120.3, 116.0, 113.1, 76.6
(ArOC), 56.7, 56.2, 50.1, 42.4, 42.3, 39.8, 39.5, 37.3, 36.5, 36.2, 35.8,
34.7, 31.9, 31.6, 28.3, 28.0, 24.3, 23.9, 22.9 (CH3), 22.6 (CH3), 21.1,
19.4 (CH3), 18.7 (CH3), 11.9 (CH3); IR (neat) 2944 (s), 2866 (s), 1609
(m), 1515 (m), 1467 (m), 1372 (m), 1245 (m), 1051 (m) cmÀ 1; HRMS
(ESI-TOF) m/z [M+H]+ calcd for C36H54O+H 503.4253, found
503.4245.
residue was purified by use of column chromatography (5.0%
EtOAc in hexanes as the eluent) to give phenolic ether 18c
(89.9 mg, 0.328 mmol) in 81% yield as a colorless oil: TLC Rf =0.35
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
1
(5.0% EtOAc in hexanes as the eluent); H NMR (CDCl3, 400 MHz) δ
7.30 (d, J=7.2 Hz, 1 H, ArH), 6.93–6.88 (m, 3 H, 3×ArH), 6.10 (s, 1 H,
C=CH), 5.26 (s, 1 H, C=CH), 3.82 (s, 3 H, ArOCH3), 3.72 (s, 3 H,
CO2CH3), 3.55 (s, 2 H, ArCH2). These spectroscopic data are in
accordance with the literature values.[54]
1-Allyl-4,5-dimethyl-2-methoxybenzene (18d). The Standard Pro-
cedure 3 was followed by use of 2-silylphenyl triflate 1b (356 mg,
1.09 mmol, 1.0 equiv), 3-methoxy-1-propene (17a, 158 mg,
2.19 mmol, 2.0 equiv), and CsF (202 mg, 1.32 mmol, 1.2 equiv) in
°
THF (3.5 mL). After the reaction mixture was stirred at 50 C for
24 h, it was quenched and worked up. The residue was purified by
use of column chromatography (3.0% EtOAc in hexanes as the
eluent) to give phenolic ether 18d (131 mg, 0.743 mmol) in 68%
yield as a colorless oil: TLC Rf =0.35 (5.0% EtOAc in hexanes as the
Deposition Number 1945287 (for 9e) contains the supplementary
crystallographic data for this paper. These data are provided free of
charge by the joint Cambridge Crystallographic Data Centre and
Fachinformationszentrum Karlsruhe Access Structures service
www.ccdc.cam.ac.uk/structures.
1
eluent); H NMR (CDCl3, 400 MHz) δ 7.37 (s, 1 H, ArH), 6.83 (s, 1 H,
ArH), 6.02–5.93 (m, 1 H, HC=C), 5.08–5.02 (m, 2 H, C=CH2), 3.78 (s, 3
H, ArOCH3), 3.41 (d, J=6.4 Hz, 2 H, ArCH2), 2.33 (s, 2 H, ArCH3), 2.22
(s, 2 H, ArCH3); 13C NMR (CDCl3, 100 MHz) δ 157.6, 137.3, 136.7,
132.1, 130.7, 129.6, 115.2, 113.8, 56.1 (ArOCH3), 34.3 (ArCH2), 20.3
(ArCH3), 19.7 (ArCH3); IR (neat) 2927 (m), 2834 (w), 1613 (s), 1584
(m), 1510 (s), 1255 (m), 1042 (m), 747 (w) cmÀ 1; HRMS (ESI-TOF) m/z
[M+H]+ calcd for C12H16O+H 177.1279, found 177.1278.
Acknowledgements
For financial support, we thank the Ministry of Science and
Technology (MOST, grant nos. 109-2113-M-007-007 and 109-2634-
F-007-023) and the Ministry of Education (grant nos. 109QR001I5
and 108QR001I5) of R.O.C. We also thank the MOST in Taiwan to
support The Featured Areas Research Center Program within the
framework of the Higher Education Sprout Project through the
Frontier Research Center on Fundamental and Applied Sciences of
Matters. Authors thank Mses. Hui-Chi Tan, Pei-Lin Chen, and Hsin-
Ru Wu of Instrumentation Center at NTHU for their assistance
with NMR-500, SXRD, and HPLC/MS-MS experiments, respectively.
γ-Asarone (18e). The Standard Procedure 3 was followed by use of
2-silylphenyl triflate 1c (365 mg, 1.04 mmol, 1.0 equiv), 3-methoxy-
1-propene (17a, 150 mg, 2.08 mmol, 2.0 equiv), and CsF (190 mg,
1.25 mmol, 1.2 equiv) in THF (4.5 mL). After the reaction mixture
°
was stirred at 50 C for 28 h, it was quenched and worked up. The
residue was purified by use of column chromatography (3.0%
EtOAc in hexanes as the eluent) to give phenolic ether 18e
(129 mg, 0.619 mmol) in 60% yield as a colorless oil: TLC Rf =0.40
1
(5.0% EtOAc in hexanes as the eluent); H NMR (CDCl3, 400 MHz) δ
6.70 (s, 1 H, ArH), 6.53 (s, 1 H, ArH), 6.01–5.93 (m, 1 H, HC=C), 5.05–
5.02 (m, 2 H, C=CH2), 3.89 (s, 3 H, OCH3), 3.82 (s, 3 H, OCH3), 3.80 (s,
3 H, OCH3), 3.39 (d, J=6.8 Hz, 2 H, ArCH2). These spectroscopic data
are in accordance with the literature values.[21]
Asaricin (18f). The Standard Procedure 3 was followed by use of 2-
silylphenyl triflate 1d (125 mg, 0.365 mmol, 1.0 equiv), 3-methoxy-
1-propene (17a, 52.6 mg, 0.730 mmol, 2.0 equiv), and CsF (66.5 mg,
0.438 mmol, 1.2 equiv) in THF (2.5 mL). After the reaction mixture
Conflict of Interest
The authors declare no conflict of interest.
°
was stirred at 50 C for 24 h, it was quenched and worked up. The
residue was purified by use of column chromatography (5.0%
EtOAc in hexanes as the eluent) to give phenolic ether 18f
(40.6 mg, 0.211 mmol) in 58% yield as a colorless oil: TLC Rf =0.30
Keywords: Aryne · 1,2-Dihydroquinoline · Domino · Epoxides ·
Phenolic ethers
1
(5.0% EtOAc in hexanes as the eluent); H NMR (CDCl3, 400 MHz) δ
6.64 (s, 1 H, ArH), 6.51 (s, 1 H, ArH), 5.97–5.88 (m, 1 H, HC=C), 6.64
(s, 1 H, ArH) 5.87 (s, 2 H, OCH2O), 5.05–4.98 (m, 2 H, C=CH2), 3.75 (s,
3 H, OCH3), 3.43 (d, J=6.4 Hz, 2 H, ArCH2). These spectroscopic data
are in accordance with the literature values.[22]
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Manuscript received: November 16, 2020
Revised manuscript received: November 27, 2020
Accepted manuscript online: November 30, 2020
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