Palladium-Catalyzed Decarboxylative Coupling of Alkynyl Carboxylic Acids and Alkenyl Tosylates for the Synthesis of Enynones

Article abstract of DOI:10.1021/acs.joc.7b02175

A palladium-catalyzed decarboxylative coupling reaction was developed for the synthesis of 3-(1-alkynyl)-2-cyclohexen-1-ones. A variety of alkynyl carboxylic acids were coupled with 3-oxocyclohexenyl tosylates to afford the corresponding enynones in good

Full text of DOI:10.1021/acs.joc.7b02175

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Article
Palladium-catalyzed decarboxylative coupling of alkynyl carboxylic
acids and alkenyl tosylates for the synthesis of enynones
Subeen Yu, Eunjeong Cho, Jimin Kim, and Sunwoo Lee
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b02175 • Publication Date (Web): 02 Oct 2017
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Palladium-catalyzed decarboxylative coupling of
alkynyl carboxylic acids and alkenyl tosylates for
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the synthesis of enynones
Subeen Yu, Eunjeong Cho, Jimin Kim, and Sunwoo Lee*
Department of Chemistry, Chonnam National University, Gwangju, 61186, Republic of Korea
Corresponding Author: S. Lee (sunwoo@chonnam.ac.kr)
Keywords: palladium, decarboxylative coupling, propiolic acid, 3-oxoalkenyl tosylate, 3-(1-
alkynyl)-2-cyclohexen-1-one
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Abstract
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A palladium-catalyzed decarboxylative coupling reaction was developed for the synthesis of 3-
(1-alkynyl)-2-cyclohexen-1-ones. A variety of alkynyl carboxylic acids were coupled with 3-
oxocyclohexenyl tosylates to afford the corresponding enynones in good to excellent yields. The
developed catalytic system is phosphine free and showed good tolerance towards various
functionalities such as chloride, cyano, nitro, ester, ketone, aldehyde, and alcohol groups. In
addition, phenylpropiolic acid exhibited higher reactivity in the reaction with alkenyl toslyate
than phenyl acetylene.
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INTRODUCTION
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Conjugated enynes have been applied in electro- and optical materials, pharmaceuticals,1 and as
useful synthetic building blocks because they can be transformed into various important
moieties.2 Among them, conjugated enynones have garnered attention in the synthesis of
bioactive agents3 and have been used as starting materials for the preparation of useful organic
molecules such as allenes,4 cyclooctatetraenes,5 pyrrolizines,6 chromenes,7 fused rings,8 and
polycyclic compounds.9
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Many synthetic methods have been developed. Specifically, allylic alcohol rearrangements,10
copper-catalyzed multicomponent reactions,11 and nucleophilic 1,2-additions12 have been
reported. The coupling reactions of 3-oxoalkenyl and alkynyl compounds are straightforward as
shown in Scheme 1. Reactions with ethoxyalkenes and alkynyl lithium or magnesium have been
used in early stage syntheses.13 However, such approaches suffer from low functional group
tolerance. To address this problem, palladium or nickel-catalyzed coupling reactions have been
developed. Alkenyl zinc, telluride, and halides have been employed in the coupling reaction with
alkynyl compounds.14 In addition, an alkenyl triflate was reacted with alkynyl stannane or silane
in the presence of a palladium catalyst.15 One of the most efficient methods is the Sonogashira
coupling of alkenyl halides and terminal alkynes.16 Alkenyl triflates were also employed as
coupling partners in the synthesis of 3-(1-alkynyl)-2-cyclohexen-1-ones.17 Fu and co-workers
reported a palladium-catalyzed coupling reaction with 3-oxocyclohex-1-enyl tosylates and
terminal acetylenes.18 They showed good yields of the coupled products; however, only one
example was shown in the case of the reaction with an aryl acetylene.
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Scheme 1. Synthesis of 3-(1-alkynyl)-2-cyclohexen-1-ones.
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Since we first reported a decarboxylative coupling reaction with an arylpropiolic acid,
continuous efforts towards the expansion of decarboxylative coupling reactions have been put
forth in our lab.19 Aryl halides are mainly used as coupling partners in the presence of palladium
or copper catalysts. Recently, we reported that aryl silane and boronic acid can also be employed
as coupling partners in the presence of a nickel catalyst.20 In addition, a variety of
decarboxylative coupling reactions have been reported.21
However, the decarboxylative coupling reaction with vinyl substrate has much less studied
than those with aryl substrate. Realizing the need for a simple and efficient method for the
decarboxylative coupling with alkenyl tosylate, we focused on a decarboxylative coupling
reaction with 3-oxocyclohex-1-enyl tosylates. Alkenyl tosylates are readily prepared, stable, and
cost efficient. Moreover, we envisioned that the facile accessibility of a variety of aryl propiolic
acids would provide diverse 3-(1-alkynyl)-2-cyclohexen-1-ones.
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RESULTS AND DISCUSSION
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First, 3-oxocyclohex-1-enyl tosylate was prepared from 1,3-cyclohexanedione and p-
toluenesulfonyl chloride in the presence of a base, and was allowed to react with phenylpropiolic
acid under various reaction conditions. The results are summarized in Table.
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Using Pd(MeCN)2Cl2 as the palladium source, various ligands were tested in the presence of
K3PO4. The results are summarized in Table 1. Chelating phosphine ligands such as dppb, dppe,
Xantphos, and Josiphos did not give satisfactory results (entries 1–4). It was found that Josiphos,
which showed good activity in the decarboxylative coupling reaction with aryltosylates and
arylpropiolic acids, was not a suitable ligand in this coupling reaction. X-Phos and PPh3 afforded
the desired products in 42% and 79% yields, respectively (entries 5 and 6). On the other hand,
PPh3, which was a good ligand in the coupling reaction with 3-oxocyclohex-1-enyl tosylate and
terminal acetylenes, also showed reasonable activity in the decarboxylative coupling reaction.
When chelating diamine-type ligands such as t-BuBipy, Me4Phen, Me2Phen, and 1,10-Phen were
employed, the yields of the products improved in most cases, except with Me2Phen (entries 7–
10). The steric hindrance of Me2Phen might reduce the yield of the product (entry 9). 1,10-Phen
was chosen as a suitable ligand (entry 10). This phosphine free system is the advantage over the
previous report.16
Among the tested palladium sources, Pd(MeCN)2Cl2 resulted in a higher yield than other
palladium sources such as Pd(allyl)Cl, Pd(OAc)2, Pd(acac)2, Pd(dba)2, and Pd2(dba)3 (entries 11–
15). When carbonate bases such as Cs2CO3, K2CO3, and Na2CO3 were employed instead of
K3PO4, the desired products formed in 59%, 70%, and 81% yields, respectively (entries 16–18).
The reactions with organic bases such as 1,8-diazabicylco(5.4.0)undec-7-ene (DBU), i-Pr2EtN,
and i-Pr2NH provided the desired products in 32%, 67%, and 83% yields, respectively (entries
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19–21). The reactions in ether-type solvents such as 1,4-dioxane and THF afforded the desired
products in higher yields than in polar solvents such as DMF, NMP, and DMSO (entries 22–26).
However, they did not result in a higher yield than that obtained in toluene.
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Table 1. Optimization of synthesis of 3-(1-phenylethynyl)-2-cyclohexen-1-ones.a
Entry
Pd
Ligand
Base
Solvent
Yield (%)b
1
Pd(CH3CN)2Cl2
Pd(CH3CN)2Cl2
Pd(CH3CN)2Cl2
Pd(CH3CN)2Cl2
Pd(CH3CN)2Cl2
Pd(CH3CN)2Cl2
Pd(CH3CN)2Cl2
Pd(CH3CN)2Cl2
Pd(CH3CN)2Cl2
Pd(CH3CN)2Cl2
Pd(allyl)Cl
Dppb
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
Cs2CO3
K2CO3
Na2CO3
DBU
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
1,4-Dioxane
THF
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30
10
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42
79
95
96
41
98
81
77
55
82
67
59
70
81
32
67
83
86
85
79
46
57
2
Dppe
3
Xantphos
Josiphos
X-Phos
4
5
6
PPh3
7
t-BuBipy
Me4Phen
Me2Phen
1,10-Phen
1,10-Phen
1,10-Phen
1,10-Phen
1,10-Phen
1,10-Phen
1,10-Phen
1,10-Phen
1,10-Phen
1,10-Phen
1,10-Phen
1,10-Phen
1,10-Phen
1,10-Phen
1,10-Phen
1,10-Phen
1,10-Phen
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Pd(OAc)2
Pd(acac)2
Pd(dba)2
Pd2(dba)3
Pd(CH3CN)2Cl2
Pd(CH3CN)2Cl2
Pd(CH3CN)2Cl2
Pd(CH3CN)2Cl2
Pd(CH3CN)2Cl2
Pd(CH3CN)2Cl2
Pd(CH3CN)2Cl2
Pd(CH3CN)2Cl2
Pd(CH3CN)2Cl2
Pd(CH3CN)2Cl2
Pd(CH3CN)2Cl2
i-Pr2EtN
i-Pr2NH
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
DMF
NMP
DMSO
aReaction conditions: 1a (0.2 mmol), 2a (0.2 mmol), Pd (0.004 mmol), ligand (0.004
o
mmol), and base (0.24 mmol) were reacted in a solvent (1.0 mL) at 60 C for 6 h.
bDetermined by gas chromatography with an internal standard.
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Ligand
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With the optimized reaction conditions in hand (i.e., Pd(MeCN)2Cl2, 1,10-Phen, and K3PO4 in
toluene), the coupling reaction was carried out at different temperatures in order to identify the
optimal reaction time and temperature. As shown in Figure 1, when the reaction was carried out
at 60 °C in toluene, the reaction was complete within 3 h and the product was obtained in 98%
yield. At 60 °C in DMF, the reaction was complete within 1 h, and the product yield was 79%;
however, the yield did not increase after 6 h. When the reaction was carried out at 25 °C, the
reaction in toluene showed a very low yield, but the reaction in DMF afforded 75% yield of the
product in 3 h. Based on these results, the optimized conditions were determined to be 60 °C in
toluene for 4 h.
Figure 1. Optimization of reaction time and temperature.
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To evaluate the scope of the methodology, a variety of arylpropiolic acids were employed in
the reaction with enone tosylates. The results are summarized in Scheme 2. As expected,
phenylpropiolic acid afforded desired product 3aa in 98% yield. Methyl- and ethyl-substituted
phenylpropiolic acids 2b, 2c, 2d, and 2e provided the corresponding enynones 3ab, 3ac, 3ad,
and 3ae in 84%, 89%, 91%, and 93% yields, respectively. The alkoxy-substituted
phenylpropiolic acids resulted in good to excellent yields of 3af, 3ag, and 3ah. Naphthyl- and
biphenyl-substituted propiolic acids gave 3ai and 3aj in 77% and 80% yields, respectively.
Interestingly, an arylpropiolic acid with a chloride group provided 3ak in 99% yield without the
concomitant coupling reaction at the chloride. The trifluoromethyl-substituted analogue gave a
low yield of 3al. Arylpropiolic acids bearing electron-withdrawing groups such as cyano, nitro,
aldehyde, and ester moieties provided 3am, 3an, 3ao, and 3ap in good to excellent yields. 3-
(Thiophen-2-yl)propiolic acid gave the corresponding product in 87% yield. The hydroxymethyl-
substituted starting material gave the desired product in 94% yield. In addition, alkyl-substituted
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propiolic acids such as hexynoic, octynoic, butynoic and pentynoic acids provided 3as, 3at, 3au
and 3av in 75%, 80%, 62% and 70% yields, respectively. However, unfortunately, the reaction
with 3-oxocyclopent-1-enyl tosylate and phenylpropiolic acid did not give the desired coupled
product 4.
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Scheme 2. Decarboxylative coupling of alkynyl carboxylic acids and 1a.a
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aReaction conditions: 1a (2.0 mmol), 2 (2.0 mmol), Pd(MeCN)2Cl2 (0.04 mmol), 1,10-
Phen (0.04mmol), and K3PO4 (2.4 mmol) were reacted in toluene (10.0 mL) at 60 ºC for
b
4 h. The numbers in parentheses are yields. 3-Oxocyclopent-1-enyl tosylate was used
instead of 1a.
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a
Scheme 3. Decarboxylative coupling of alkynyl carboxylic acids and 1b.
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aReaction conditions: 1b (2.0 mmol), 2 (2.0 mmol), Pd(MeCN)2Cl2 (0.04 mmol), 1,10-
Phen (0.04 mmol), and K3PO4 (2.4 mmol) were reacted in toluene (10.0 mL) at 60 ºC for
4 h. The numbers in parentheses are yield.
To expand the scope of enone tosylates, 5,5-dimethyl-3-oxocyclohex-1-enyl tosylate (1b) was
also employed. As shown in Scheme 3, the reactions with a variety of arylpropiolic acids
provided the desired coupled products in good to excellent yields. Compared to the reactions of
alkenyl tosylate 1a, the reactions with 1b gave similar product yields in most cases. In addition,
similar functional group tolerance was shown in the reaction with 1b. However, the employment
of an acyclic alkenyl tosylate was unsuccessful. When we attempted to react with phenyl
propiolic acid and (E)-2-phenylethenoyl tosylate, the desired coupled product was not formed
under this optimized condition.
To investigate the effect of substituents, phenylpropiolic acid (2a) was allowed to react with
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substituted arylpropioic acids such as 3ad, 3ag, and 3ap. The results are summarized in Table 2.
In the competitive reactions, phenylpropiolic acid gave a higher yield than 2d and 2p, which had
methyl and ester groups, respectively (entries 1 and 2). Methoxy-substituted arylpropiolic acid
2g afforded 3ag in a slightly higher yield than 3aa (entry 3). From these results, we postulated
that the reactivity of the arylpropiolic acid was not related to the substituent on the phenyl ring.
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Table 2. Substituent effect on arylpropiolic acids.a
Product (Yield)b
Ratio
Entry
Sub-PPA
3aa/Sub-Prod
1/0.7
3aa
Sub-Prod
3ad (34%)
3ap (36%)
3ag (45%)
1
2
3
2d (R = Me)
2p (R = CO2Me)
2g (R = OMe)
3aa (50%)
3aa (41%)
3aa (41%)
1/0.9
1/1.1
aReaction conditions: 1a (0.3 mmol), 2a (0.3 mmol), Sub-PPA (0.3 mmol),
Pd(MeCN)2Cl2 (0.006 mmol), 1,10-Phen (0.006 mmol), and K3PO4 (0.6 mmol) were
reacted in toluene (1.5 mL) at 60 °C for 4 h. bDetermined by gas chromatography with an
internal standard.
Competitive experiments were carried out in order to compare the relative reactivity of terminal
alkynes and alkynyl carboxylic acids towards alkenyl tosylates (Table 3). When equal amounts
of para-tolylpropiolic acid and phenylacetylene were allowed to react with alkenyl tosylate 1a
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under the optimized conditions, the decarboxylative coupling product formed at a 4.7/1 ratio
over the Sonogashira coupling product (entry 1). To account for electronic effects of the
substituents on the phenyl rings, phenylpropiolic acid and para-tolylacetylene were employed in
the competitive reaction. The decaroxylative coupling product still formed at a 3.9/1 ratio over
the Sonogashira coupling product. Accordingly, we determined that the decarboxylic coupling
was much more reactive than the Sonogashira coupling in the reaction with alkenyl tosylate 1a.
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Table 3. Competitive decarboxylative and Sonogashira coupling reactions.a
Product (Yield)b
Ratio
Deca-Prod/
Sono-Prod
4.7/1
Entry
R1
R2
Deca-Prod
Sono-Prod
1
2
H
Me
H
3aa (71%)
3ad (70%)
3ad (15%)
3aa (18%)
Me
3.9/1
aReaction conditions: 1a (0.3 mmol), arylpropiolic acid (0.3 mmol), arylalkyne (0.3 mmol),
Pd(MeCN)2Cl2 (0.006 mmol), 1,10-Phen (0.006 mmol), and K3PO4 (0.6 mmol) were reacted in
toluene (1.5 mL) at 60 °C for 4 h. bDetermined by gas chromatography with an internal standard.
Propiolic acid reacted with aryl halides to produce symmetrically diaryl alkynes. To evaluate the
reactivity of propiolic acids towards alkenyl tosylates 1a, propiolic acids were allowed to react
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with 2 equivalents of 1a under the optimized conditions. As shown in Scheme 4, disubstituted
alkynes 4 was formed in 60% yield.
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Scheme 4. Synthesis of symmetric dialkenyl alkynes.a
aReaction conditions: 1a (2.0 mmol), propiolic acid (1.0 mmol), Pd(MeCN)2Cl2 (0.004
mmol), 1,10-Phen (0.004 mmol), and K3PO4 (3.0 mmol) were reacted in toluene (4.0
mL) at 60 ºC for 12 h. The numbers in parentheses are yield.
CONCLUSION
In conclusion, we developed a decarboxylative coupling reaction between alkenyl carboxylic
acids and 3-oxocyclohex-1-enyl tosylates (1a and 1b) in the presence of a palladium catalyst.
This catalytic system is phosphine free and works under mild conditions. The decarboxylative
coupling reactions provided the desired products in good to excellent yields and showed good
tolerance towards various functional groups such as chloride, cyano, nitro, aldehyde, ester,
ketone, and alcohol moieties. Toluene was determined to be the best solvent, but DMF afforded a
higher yield than toluene at 25 °C. Competitive experiments with phenylpropiolic acids and
substituted arylpropilic acids confirmed that there were no substituent effects. Notably,
phenylpropiolic acid showed a higher reactivity than phenylacetylene.
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EXPERIMENTAL SECTION
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General Experimental Procedure
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Decarboxylative coupling reactions of alkynyl carboxylic acids and alkenyl tosylates:
Alkynyl carboxylic acid (2.0 mmol), 1,10-phenanthroline (7 mg, 0.04 mmol),
bis(acetonitrile)dichloropalladium(II) (10 mg, 0.04 mmol), K3PO4 (849 mg, 4.0 mmol), alkenyl
tosylate (2.0 mmol), and toluene (6.0 mL) were added to the reaction vial. The mixture was
stirred at 60 °C for 4 h. The mixture was filtered once the reaction was complete, the filtrate was
washed with water/brine, and the aqueous solution was extracted with Et2O. The organic layer
was dried over magnesium sulfate. Evaporation of the solvent under reduced pressure provided
the crude product, which was purified by column chromatography on silica gel.(eluent : pentane /
ethyl acetate = 5 / 1)
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3-(Phenylethynyl)cyclohex-2-enone (3aa)17c
3-Oxocyclohex-1-enyl tosylate (1a) (533mg, 2.0 mmol) and 3-phenylpropiolic acid (2a) (292 mg,
2.0 mmol) afforded 3-(phenylethynyl)cyclohex-2-enone (3aa) (385 mg, 1.96 mmol, 98% yield );
Yellow oil; 1H NMR (500 MHz, CDCl3) δ 7.50-7.48 (m, 2H), 7.38-7.34 (m, 3H), 6.29 (t, J = 1.7
Hz, 1H), 2.55 (td, J = 6.1 Hz, 1.7 Hz, 2H), 2.46-2.43 (m, 2H), 2.10-2.05 (m, 2H); 13C{1H} NMR
(126 MHz, CDCl3) δ 198.7, 143.3, 132.4, 131.9, 129.4, 128.5, 122.0, 99.7, 88.4, 37.3, 30.5, 22.6;
MS (EI) m/z = 196 (M+).
3-(o-Tolylethynyl)cyclohex-2-enone. (3ab)
3-Oxocyclohex-1-enyl tosylate (1a) (533mg, 2.0 mmol) and 3-(o-tolyl)propiolic acid (2b) (320
mg, 2.0 mmol) afforded 3-(o-tolylethynyl)cyclohex-2-enone (3ab) (353 mg, 1.68 mmol, 84%
yield ); Yellow solid; mp 42.3-44.0 oC; 1H NMR (500 MHz, CDCl3) δ 7.45 (dd, J = 7.6 Hz, 1.0
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Hz, 1H), 7.28 (td, J = 7.5 Hz, 1.3 Hz, 1H), 7.24-7.23 (m, 1H), 7.19-7.16 (m, 1H), 6.30 (t, J = 1.6
Hz, 1H), 2.57 (td, J = 6.1 Hz, 1.6 Hz, 2H), 2.47-2.44 (m, 5H), 2.12-2.06 (m, 2H); 13C{1H} NMR
(126 MHz, CDCl3) ) δ 198.7, 143.6, 140.7, 132.2, 132.1, 129.7, 129.6, 125.8, 121.7, 98.8, 92.3,
37.3, 30.6, 22.6, 20.6; HRMS (EI-MSES double focusing) m/z: cacld. for C15H14O (M+):
210.1045, found: 210.1046.
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3-(m-Tolylethynyl)cyclohex-2-enone (3ac)
3-Oxocyclohex-1-enyl tosylate (1a) (533mg, 2.0 mmol) and 3-(m-tolyl)propiolic acid (2c) (320
mg, 2.0 mmol) afforded 3-(m-tolylethynyl)cyclohex-2-enone (3ac) (374 mg, 1.78 mmol, 89%
yield ); Yellow oil; 1H NMR (500 MHz, CDCl3) δ 7.33-7.32 (m, 1H), 7.32-7.30(m, 1H), 7.26 (t,
J = 7.4 Hz, 1H), 7.22-7.19 (m, 1H), 6.30 (t, J = 1.7 Hz, 1H), 2.56 (td, J = 6.1Hz, 1.6Hz, 2H),
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2.46 (t, J = 6.7 Hz, 5H), 2.11-2.06 (m, 2H); C{1H} NMR (126 MHz, CDCl3) δ 198.8, 143.5,
138.3, 132.5, 132.3, 130.4, 129.1, 128.4, 121.8, 100.1, 88.1, 37.3, 30.6, 22.6, 21.2; HRMS (EI-
MSES double focusing) m/z cacld. for C15H14O (M+): 210.1045, found: 210.1045.
3-(p-Tolylethynyl)cyclohex-2-enone (3ad)
3-Oxocyclohex-1-enyl tosylate (1a) (533mg, 2.0 mmol) and 3-(p-tolyl)propiolic acid (1d) (320
mg, 2.0 mmol) afforded 3-(p-tolylethynyl)cyclohex-2-enone (3ad) (383 mg, 1.82 mmol, 91%
yield ); Yellow solid; mp 79.1-82.0 oC; 1H NMR (500 MHz, CDCl3) δ 7.40 (d, J = 8.1 Hz, 2H),
7.18 (d, J = 8.5 Hz, 2H), 6.29 (t, J = 1.6 Hz, 1H), 2.56 (td, J = 6.1 Hz, 1.6 Hz, 2H), 2.46 (t, J =
6.8 Hz, 2H), 2.39 (s, 3H), 2.11-2.06 (m, 2H); 13C{1H} NMR (126 MHz, CDCl3) δ 198.8, 143.6,
139.9, 132.1, 131.9, 129.3, 118.9, 100.2, 88.0, 37.4, 30.6, 22.7, 21.6; HRMS (EI-MSES double
focusing) m/z cacld. for C15H14O (M+): 210.1045, found: 210.1048.
3-((4-Ethylphenyl)ethynyl)cyclohex-2-enone (3ae)
3-Oxocyclohex-1-enyl tosylate (1a) (533mg, 2.0 mmol) and 3-(4-ethylphenyl)propiolic acid (2e)
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(348 mg, 2.0 mmol) afforded 3-((4-ethylphenyl)ethynyl)cyclohex-2-enone (3ae) (417 mg, 1.86
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1
mmol, 93% yield ); Yellow oil; H NMR (500 MHz, CDCl3) δ 7.42 (d, J = 8.3 Hz, 2H), 7.21-
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2.45 (t, J = 6.7 Hz, 2H), 2.11-2.06 (m, 2H), 1.25 (t, J = 7.6 Hz, 3H); C{1H} NMR (126 MHz,
CDCl3) δ 198.8, 146.2, 143.7, 132.1, 132.0, 128.1, 119.1, 100.2, 88.0, 37.4, 30.6, 28.9, 22.6, 15.3;
HRMS (EI-MSES double focusing) m/z cacld. for C16H16O (M+): 224.1201, found: 224.1200.
3-((2-Methoxyphenyl)ethynyl)cyclohex-2-enone (3af)
3-Oxocyclohex-1-enyl tosylate (1a) (533mg, 2.0 mmol) and 3-(2-methoxyphenyl)propiolic acid
(2f) (352 mg, 2.0 mmol) afforded 3-((2-methoxyphenyl)ethynyl)cyclohex-2-enone (3af) (367 mg,
1.62 mmol, 81% yield ); Yellow oil; 1H NMR (500 MHz, CDCl3) δ 7.45 (dd, J = 7.5 Hz, 1.6 Hz,
1H), 7.39-7.35 (m, 1H), 6.95 (td, J = 7.5 Hz, 1.0 Hz, 1H), 6.91 (d, J = 8.4 Hz, 1H), 6.33 (t, J =
1.6 Hz, 1H), 3.91 (s, 3H), 2.59 (td, J = 6.1 Hz, 1.6 Hz, 2H), 2.47-2.44 (m, 2H), 2.11-2.06 (m,
2H); 13C{1H} NMR (126 MHz, CDCl3) δ 198.8, 160.2, 143.7, 133.8, 132.2, 131.1, 120.6, 111.2,
110.8, 96.5, 92.5, 55.8, 37.4, 30.6, 22.7; HRMS (EI-MSES double focusing) m/z cacld. for
C15H14O2 (M+): 226.0994, found: 226.0992.
3-((4-Methoxyphenyl)ethynyl)cyclohex-2-enone (3ag)17c
3-Oxocyclohex-1-enyl tosylate (1a) (533mg, 2.0 mmol) and 3-(4-methoxyphenyl)propiolic acid
(2g) (352 mg, 2.0 mmol) afforded 3-((4-methoxyphenyl)ethynyl)cyclohex-2-enone (3ag) (430
mg, 1.9 mmol, 95% yield ); Yellow solid; mp 95.0-96.0 oC; 1H NMR (500 MHz, CDCl3) δ 7.44-
7.41 (m, 2H), 6.89-6.86 (m, 2H), 6.25 (t, J = 1.6 Hz. 1H), 3.82 (s, 3H), 2.53 (td, J = 6.1 Hz, 1.6
Hz, 2H), 2.44-2.41 (m, 2H), 2.08-2.03(m, 2H); 13C{1H} NMR (126 MHz, CDCl3) δ 198.6, 160.5,
143.7, 133.6, 131.5, 114.1, 113.9, 100.3, 87.6, 55.3, 37.2, 30.5, 22.6; MS (EI) m/z = 226 (M+).
3-(Benzo[d][1,3]dioxol-5-ylethynyl)cyclohex-2-enone (3ah)
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3-Oxocyclohex-1-enyl tosylate (1a) (533mg, 2.0 mmol) and 3-(benzo[d][1,3]dioxol-5-
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6
yl)propiolic acid
(2h) (380 mg, 2.0 mmol) afforded 3-(benzo[d][1,3]dioxol-5-
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ylethynyl)cyclohex-2-enone (3ah) (389 mg, 1.62 mmol, 81% yield ); Yellow solid; mp 119.0-
120.4 oC; 1H NMR (500 MHz, CDCl3) δ 7.03 (dd, J = 8.1, 1.6Hz, 1H), 6.93 (d, J = 1.6 Hz, 1H),
6.80 (d, J = 8.1 Hz, 1H), 6.26 ( t, J = 1.6 Hz, 1H), 6.01 (s, 2H), 2.53 (td, J = 6.1 Hz, 1.6Hz, 2H),
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2.44 (t, J = 6.7 Hz, 2H), 2.09-2.04 (m, 2H); C{1H} NMR (126 MHz, CDCl3) δ 198.7, 149.0,
147.6, 143.5, 131.9, 127.2, 115.1, 111.7, 108.7, 101.6, 100.1, 87.3, 37.3, 30.5, 22.6; HRMS (EI-
MSES double focusing) m/z cacld. for C15H12O3 (M+): 240.0786, found: 240.0784.
3-(Naphthalen-1-ylethynyl)cyclohex-2-enone (3ai)
3-Oxocyclohex-1-enyl tosylate (1a) (533mg, 2.0 mmol) and 3-(naphthalen-1-yl)propiolic acid
(2i) (392 mg, 2.0 mmol) afforded 3-(naphthalen-1-ylethynyl)cyclohex-2-enone (3ai) (379 mg,
o
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1.54 mmol, 77% yield ); Yellow solid; mp 87.0-88.1 C; H NMR (500 MHz, CDCl3) δ 8.29-
8.27 (m, 1H), 7.92-7.88 (m, 2H), 7.75 (dd, J = 7.2 Hz, 1.2 Hz, 1H), 7.64-7.55 (m, 2H) 7.48 (dd, J
= 8.2 Hz, 7.2 Hz, 1H) 6.44 (t, J = 1.7 Hz, 1H), 2.69 (td, J = 6.1 Hz, 1.6 Hz, 2H), 2.50 (t, J = 6.7
Hz, 2H), 2.18-2.13 (m, 2H); 13C{1H} NMR (126 MHz, CDCl3) δ 198.7, 143.4, 133.1, 133.0,
132.4, 131.3, 130.2, 128.5, 127.2, 126.7, 125.8, 125.2, 119.5, 97.9, 92.3, 37.4, 30.6, 22.7; HRMS
(EI-MSES double focusing) m/z cacld. for C18H14O (M+): 246.0145, found: 246.1047.
3-([1,1'-Biphenyl]-4-ylethynyl)cyclohex-2-enone (3aj)
3-Oxocyclohex-1-enyl tosylate (1a) (533mg, 2.0 mmol) and 3-([1,1'-biphenyl]-4-yl)propiolic
acid (2j) (444 mg, 2.0 mmol) afforded 3-([1,1'-biphenyl]-4-ylethynyl)cyclohex-2-enone (3aj)
(436 mg, 1.6 mmol, 80% yield ); Yellow solid; mp 87.0-88.0 oC; 1H NMR (500 MHz, CDCl3) δ
7.63-7.60 (m, 4H), 7.59-7.57 (m, 2H), 7.49-7.45 (m, 2H), 7.39 (tt, J = 4.2 Hz, 1.5 Hz, 1H), 6.33
(t, J = 1.7 Hz, 1H), 2.59 (td, J = 6.1 Hz, 1.6 Hz, 2H), 2.49-2.46 (m, 2H), 2.13-2.08 (m, 2H);
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13C{1H} NMR (126 MHz, CDCl3) δ 198.7, 143.4, 142.2, 140.0, 132.4, 132.3, 128.9, 128.0, 127.2,
127.0, 120.8, 99.7, 89.1, 37.4, 30.5, 22.7; HRMS (EI-MSES double focusing) m/z cacld. for
C20H16O (M+): 272.1201, found: 272.1200.
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3-((4-Chlorophenyl)ethynyl)cyclohex-2-enone (3ak)
3-Oxocyclohex-1-enyl tosylate (1a) (533mg, 2.0 mmol) and 3-(4-chlorophenyl)propiolic acid
(2k) (361 mg, 2.0 mmol) afforded 3-((4-chlorophenyl)ethynyl)cyclohex-2-enone (3ak) (457 mg,
1.98 mmol, 99% yield ); Yellow solid; mp 101.5-103.0 oC 1H NMR (500 MHz, CDCl3) δ 7.43 (d,
J = 8.8 Hz, 2H), 7.35 (d, J = 8.8 Hz, 2H), 6.30 (t, J = 1.7 Hz, 1H), 2.56 (td, J = 6.1 Hz, 1.7Hz,
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2H), 2.46 (t, J = 6.7 Hz, 2H), 2.12-2.07 (m, 2H); C{1H} NMR (126 MHz, CDCl3) δ 198.6,
142.9, 135.6, 133.1, 132.7, 128.9, 120.5, 98.3, 89.2, 37.3, 30.4, 22.6; HRMS (EI-MSES double
focusing) m/z cacld. for C14H11ClO (M+): 230.0498, found: 230.0496.
3-((4-(Trifluoromethyl)phenyl)ethynyl)cyclohex-2-enone (3al)
3-Oxocyclohex-1-enyl
tosylate
(1a)
(533mg,
2.0
mmol)
and
3-(4-
(trifluoromethyl)phenyl)propiolic acid (2l) (428 mg, 2.0 mmol) afforded 3-((4-
(trifluoromethyl)phenyl)ethynyl)cyclohex-2-enone (3al) (285 mg, 1.08 mmol, 54% yield );
Brown oil; 1H NMR (500 MHz, CDCl3) δ 7.63-7.58 (m, 4H), 6.32 (t, J = 1.7 Hz, 1H), 2.56 (td, J
= 6.1 Hz, 1.7 Hz, 2H), 2.48-2.45 (m, 2H), 2.12-2.07 (m, 2H); 13C{1H} NMR (126 MHz, CDCl3)
δ 198.4, 142.4, 133.1, 132.1, 130.9(q, JC-F = 32.8 Hz), 125.7 (q, JC-F = 1.3 Hz), 125.4 (q, JC-F
=
3.8 Hz), 123.6 (q, JC-F = 272.9 Hz), 97.4, 90.2, 37.3, 30.2, 22.5; HRMS (EI-MSES double
focusing) m/z cacld. for C15H11F3O (M+): 264.0762, found: 264.0765.
4-((3-Oxocyclohex-1-en-1-yl)ethynyl)benzonitrile (3am)
3-Oxocyclohex-1-enyl tosylate (1a) (533mg, 2.0 mmol) and 3-(4-cyanophenyl)propiolic acid
(2m) (342 mg, 2.0 mmol) afforded 4-((3-oxocyclohex-1-en-1-yl)ethynyl)benzonitrile (3am) (380
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mg, 1.72 mmol, 86% yield ); Yellow solid; mp 114.6-115.0 C; H NMR (500 MHz, CDCl3) δ
7.65 (d, J = 8.0 Hz, 2H), 7.57 (d, J = 8.7 Hz, 2H), 6.32 (t, J = 1.7 Hz, 1H), 2.55 (td, J = 6.1Hz,
1.7 Hz, 2H), 2.47 (t, J = 6.7 Hz, 2H), 2.12-2.07 (m, 2H); 13C{1H} NMR (126 MHz, CDCl3)
198.4, 142.0, 133.5, 132.3, 132.1, 126.8, 118.2, 112.7, 96.9, 91.9, 37.3, 30.2, 22.6; HRMS (EI-
MSES double focusing) m/z cacld. for C15H11NO (M+): 221.0841, found: 221.0842.
3-((4-Ntrophenyl)ethynyl)cyclohex-2-enone (3an)
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(382 mg, 2.0 mmol) afforded 3-((4-nitrophenyl)ethynyl)cyclohex-2-enone (3an) (367 mg, 1.52
mmol, 76% yield ); Yellow oil; 1H NMR (500 MHz, CDCl3) δ 8.25-8.22 (m, 2H), 7.65-7.63 (m,
2H), 6.34 (t, J = 1.7 Hz, 1H), 2.56 (td, J = 6.1 Hz, 1.7 Hz, 2H), 2.49-2.46 (m, 2H), 2.13-2.08 (m,
2H); C{1H} NMR (126 MHz, CDCl3) δ 198.3, 147.7, 141.9, 133.7, 132.7, 128.7, 123.7, 96.5,
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92.6, 37.3, 30.2, 22.6; HRMS (EI-MSES double focusing) m/z cacld. for C14H11NO3 (M+):
241.0739, found: 241.0737.
4-((3-Oxocyclohex-1-en-1-yl)ethynyl)benzaldehyde (3ao)
3-Oxocyclohex-1-enyl tosylate (1a) (533mg, 2.0 mmol) and 3-(4-formylphenyl)propiolic acid
(2o) (348 mg, 2.0 mmol) afforded 4-((3-oxocyclohex-1-en-1-yl)ethynyl)benzaldehyde (3ao) (368
o
1
mg, 1.64 mmol, 82% yield ); White solid; mp 106.0-108.0 C; H NMR (500 MHz, CDCl3) δ
10.1 (s, 1H), 7.90-7.88 (m, 2H), 7.66-7.64 (m, 2H), 6.34 (t, J = 1.7 Hz, 1H), 2.58 (td, J = 6.1 Hz,
1.7 Hz, 2H), 2.49-2.46 (m, 2H), 2.13-2.08 (m, 2H); C{1H} NMR (126 MHz, CDCl3) δ 198.4,
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191.2, 142.3, 136.2, 133.3, 132.4, 129.6, 128.0, 97.8, 91.6, 37.3, 30.3, 22.6; HRMS (EI-MSES
double focusing) m/z cacld. for C15H12O2 (M+): 224.0837, found: 224.0837.
Mthyl 4-((3-oxocyclohex-1-en-1-yl)ethynyl)benzoate (3ap)
3-Oxocyclohex-1-enyl
tosylate
(1a)
(533mg,
2.0
mmol)
and
3-(4-
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(methoxycarbonyl)phenyl)propiolic acid (2p) (408 mg, 2.0 mmol) afforded methyl 4-((3-
oxocyclohex-1-en-1-yl)ethynyl)benzoate (3ap) (463 mg, 1.82 mmol, 91% yield ); Whtie solid;
mp 111.2-113.1 oC; 1H NMR (500 MHz, CDCl3) δ 8.01 (d, J = 8.7 Hz, 2H), 7.53 (d, J = 8.7 Hz,
2H), 6.30 (t, J = 1.7 Hz, 1H), 3.92 (s, 3H), 2.54 (td, J = 6.1 Hz, 1.7 Hz, 2H), 2.44(t, J = 6.7 Hz,
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2H), 2.10-2.05 (m, 2H); C{1H} NMR (126 MHz, CDCl3) δ 198.5, 166.3, 142.6, 133.1, 131.8,
130.5, 129.6, 126.5, 98.1, 90.5, 52.3, 37.3, 30.3, 22.6; HRMS (EI-MSES double focusing) m/z
cacld. for C16H14O3 (M+): 254.0943, found: 254.0944.
3-(Tiophen-2-ylethynyl)cyclohex-2-enone (3aq)
3-Oxocyclohex-1-enyl tosylate (1a) (533mg, 2.0 mmol) and 3-(thiophen-2-yl)propiolic acid (2q)
(304 mg, 2.0 mmol) afforded 3-(thiophen-2-ylethynyl)cyclohex-2-enone (3aq) (352 mg, 1.74
mmol, 87% yield ); Brown oil; 1H NMR (500 MHz, CDCl3) δ 7.40 (dd, J = 5.1 Hz, 1.1 Hz, 1H),
7.33 (dd, J = 3.7 Hz, 1.1 Hz, 1H), 7.05 (dd, J = 5.1 Hz, 3.7 Hz, 1H), 6.28 (t, J = 1.6 Hz, 1H),
2.55 (td, J = 6.1 Hz, 1.6 Hz, 2H), 2.45 (t, J = 6.7 Hz, 2H), 2.11-2.06 (m, 2H); C{1H} NMR
13
(126 MHz, CDCl3) δ 198.5, 142.9, 133.7, 131.9, 129.4, 127.5, 121.9, 93.1, 92.4, 37.3, 30.2, 22.6;
HRMS (EI-MSES double focusing) m/z cacld. for C12H10OS (M+): 202.0452, found: 202.0455.
3-((4-(Hydroxymethyl)phenyl)ethynyl)cyclohex-2-enone (3ar)
3-Oxocyclohex-1-enyl
tosylate
(1a)
(533mg,
2.0
mmol)
and
3-(4-
(hydroxymethyl)phenyl)propiolic acid (2r) (352 mg, 2.0 mmol) afforded 3-((4-
(hydroxymethyl)phenyl)ethynyl)cyclohex-2-enone (3ar) (425 mg, 1.88 mmol, 94% yield );
White solid; mp 103.6-105.2 oC; 1H NMR (500 MHz, CDCl3) δ 7.50 (d, J = 8.3 Hz, 2H), 7.38 (d,
J = 8.6 Hz, 2H), 6.30 (t, J = 1.65 Hz, 1H), 4.74 (s, 2H), 2.57 (td, J = 6.1Hz, 1.6Hz, 2H), 2.46 (t, J
= 6.73 Hz, 2H), 2.12-2.06 (m, 2H), 1.74 (br, s, 1H); C{1H} NMR (126 MHz, CDCl3) δ 198.7,
13
143.4, 142.4, 132.4, 132.1, 126.8, 121.1, 99.6, 88.5, 64.8, 37.3, 30.5, 22.6; HRMS (EI-MSES
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double focusing) m/z cacld. for C15H14O2 (M+): 226.0994, found: 226.0993.
3-(Pent-1-yn-1-yl)cyclohex-2-enone (3as)
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3-Oxocyclohex-1-enyl tosylate (1a) (533mg, 2.0 mmol) and hex-2-ynoic acid (2s) (224 mg, 2.0
mmol) afforded 3-(pent-1-yn-1-yl)cyclohex-2-enone (3as) (243 mg, 1.5 mmol, 75% yield );
Yellow oil; 1H NMR (500 MHz, CDCl3) δ 6.15 (t, J = 1.6 Hz, 1H), 2.45-2.38 (m, 6H), 2.05-2.00
(m, 2H), 1.64-1.57 (m, 2H), 1.02 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (126 MHz, CDCl3) δ 199.0,
144.6, 131.9, 102.2, 80.6, 37.3, 30.9, 22.6, 21.8, 21.7, 13.5; HRMS (EI-MSES double focusing)
m/z cacld. for C11H14O (M+): 162.1045, found: 162.1046.
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3-(Hept-1-yn-1-yl)cyclohex-2-enone (3at)
3-Oxocyclohex-1-enyl tosylate (1a) (533mg, 2.0 mmol) and oct-2-ynoic acid (2t) (280 mg, 2.0
mmol) afforded 3-(Hept-1-yn-1-yl)cyclohex-2-enone (3at) (296 mg, 1.6 mmol, 80% yield );
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Yellow oil; H NMR (500 MHz, CDCl3) 6.13 (t, J = 1.6 Hz, 1H), 2.42-2.37 (m, 6H), 2.03-1.98
13
(m, 2H), 1.59-1.53 (m, 2H), 1.41-1.29 (m, 4H), 0.91 (t, J = 7.2 Hz, 3H); C{1H} NMR (126
MHz, CDCl3) δ 199.1, 144.7, 131.8, 102.5, 80.4, 37.3, 31.0, 30.9, 28.0, 22.6, 22.1, 19.8, 13.9;
HRMS (EI-MSES double focusing) m/z cacld. for C13H18O (M+): 190.1358, found: 190.1358.
3-(Prop-1-yn-1-yl)cyclohex-2-enone (3au)13b
3-Oxocyclohex-1-enyl tosylate (1a) (533mg, 2.0 mmol) and but-2-ynoic acid (2u) (168 mg, 2.0
mmol) afforded 3-(Prop-1-yn-1-yl)cyclohex-2-enone (3au) (166mg, 1.24mmol, 61% yield );
Yellow oil; 1H NMR (500 MHz, CDCl3) 6.13 (s, 1H), 2.43-2.37 (m, 4H), 2.06 (s, 3H), 2.03-1.98
(m, 2H); 13C{1H} NMR (126 MHz, CDCl3) δ199.0, 144.6, 131.9, 97.8, 79.6, 37.2, 30.7, 22.5, 4.8;
MS (EI) m/z = 134 (M+).
3-(But-1-yn-1-yl)cyclohex-2-enone (3av)
3-Oxocyclohex-1-enyl tosylate (1a) (533mg, 2.0 mmol) and pent-2-ynoic acid (2v) (196 mg, 2.0
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mmol) afforded 3-(But-1-yn-1-yl)cyclohex-2-enone (3av) (207mg, 1.4mmol, 70% yield );
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Yellow oil; H NMR (500 MHz, CDCl3) 6.12 (t, J = 1.6 Hz, 1H), 2.42-2.36 (m, 6H), 2.02-1.96
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(m, 2H), 1.18 (t, J = 7.5 Hz, 3H); 13C{1H} NMR (126 MHz, CDCl3) δ199.0, 144.6, 131.9, 103.5,
79.7, 37.3, 30.8, 22.6, 13.5, 13.4; HRMS (EI-MSES double focusing) m/z cacld. for C10H12O
(M+): 148.0888, found: 148.0886
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5,5-Dimethyl-3-(phenylethynyl)cyclohex-2-enone (3ba)14b
5,5-Dimethyl-3-oxocyclohex-1-enyl tosylate (1b) (589 mg, 2.0 mmol) 3-phenylpropiolic acid
(2a) (292 mg, 2.0 mmol) afforded 5,5-dimethyl-3-(phenylethynyl)cyclohex-2-enone (3ba) (440
mg, 1.96 mmol, 98% yield ); Yellow oil; 1H NMR (500 MHz, CDCl3) δ 7.51-7.49 (m, 2H), 7.40-
7.35 (m, 3H), 6.31 (t, J = 1.7 Hz, 1H), 2.45 (d, J = 1.7 Hz, 2H), 2.30 (s, 2H), 1.11 (s, 6H);
13C{1H} NMR (126 MHz, CDCl3) δ 199.0, 141.2, 131.9, 131.3, 129.4, 128.5, 122.0, 99.3, 88.7,
51.1, 44.3, 33.8, 28.1; MS (EI) m/z = 224 (M+).
5,5-Dimethyl-3-(o-tolylethynyl)cyclohex-2-enone (3bb)16b
5,5-Dimethyl-3-oxocyclohex-1-enyl tosylate (1b) (589 mg, 2.0 mmol3-(o-tolyl)propiolic acid
(2b) (320 mg, 2.0 mmol) afforded 5,5-dimethyl-3-(o-tolylethynyl)cyclohex-2-enone (3bb) (405
mg, 1.7 mmol, 85% yield ); Yellow oil; 1H NMR (500 MHz, CDCl3) δ 7.45 (dd, J = 7.6 Hz, 1.3
Hz, 1H), 7.28 (td, J = 7.4 Hz, 1.3 Hz, 1H), 7.24-7.22 (m, 1H), 7.17 (tdd, J = 7.8 Hz, 1.5 Hz, 0.6
Hz, 1H), 6.30 (t, J = 1.7 Hz, 1H), 2.45 (s, 3H), 2.44 (d, J = 1.7 Hz, 2H), 2.29 (s, 2H), 1.10 (s, 6H);
13C{1H} NMR (126 MHz, CDCl3) δ 198.9, 141.3, 140.7, 132.2, 130.9, 129.6, 129.5, 125.7, 121.7,
98.4, 92.6, 60.0, 44.3, 33.7, 28.1, 20.6; MS (EI) m/z = 238 (M+).
5,5-Dimethyl-3-(p-tolylethynyl)cyclohex-2-enone (3bd)
5,5-Dimethyl-3-oxocyclohex-1-enyl tosylate (1b) (589 mg, 2.0 mmol) 3-(p-tolyl)propiolic acid
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(2d) (320 mg, 2.0 mmol) afforded 5,5-dimethyl-3-(p-tolylethynyl)cyclohex-2-enone (3bd) (424
5
6
o
1
mg, 1.78 mmol, 89% yield ); Yellow solid; mp 59.2-61.0 C; H NMR (500 MHz, CDCl3) δ
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8
9
7.40-7.38 (m, 2H), 7.18-7.16 (m, 2H), 6.29 (t, J = 1.7 Hz, 1H), 2.43 (d, J = 1.7 Hz, 2H), 2.38 (s,
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3H), 2.30 (s, 2H), 1.10 (s, 6H); C{1H} NMR (126 MHz, CDCl3) δ 199.0, 141.2, 139.8, 131.9,
131.3, 129.4, 128.5, 122.0, 99.3, 88.7, 51.1, 44.3, 33.8, 28.1; HRMS (EI-MSES double focusing)
m/z cacld. for C17H18O (M+): 238.1358, found: 238.1355.
3-((2-Methoxyphenyl)ethynyl)-5,5 dimethylcyclohex-2-enone (3bf)16b
5,5-Dimethyl-3-oxocyclohex-1-enyl tosylate (1b) (589 mg, 2.0 mmol) 3-(2-
methoxyphenyl)propiolic acid (2f) (352 mg, 2.0 mmol) afforded 3-((2-methoxyphenyl)ethynyl)-
5,5-dimethylcyclohex-2-enone (3bf) (443 mg, 1.74 mmol, 87% yield ); Brown oil; 1H NMR (500
MHz, CDCl3) δ 7.45-7.43 (m, 1H), 7.35 (ddd, J = 8.4 Hz, 7.5 Hz, 1.7 Hz, 1H), 6.94 (td, J = 7.5
Hz, 1.0 Hz, 1H), 6.90 (dd, J = 8.4 Hz, 0.5 Hz, 1H), 6.32 (t, J = 1.7 Hz, 1H), 3.90 (s, 3H), 2.46 (d,
J = 1.7 Hz, 2H), 2.29 (s, 2H), 1.09 (s, 6H); C{1H} NMR (126 MHz, CDCl3) δ 199.1, 160.1,
13
141.6, 133.8, 131.1, 131.0, 120.5, 111.1, 110.7, 96.1, 92.7, 55.8, 51.0, 44.3, 33.7, 28.1; MS (EI)
m/z = 254 (M+).
3-(Benzo[d][1,3]dioxol-5-ylethynyl)-5,5-dimethylcyclohex-2-enone (3bh)
5,5-Dimethyl-3-oxocyclohex-1-enyl tosylate (1b) (589 mg, 2.0 mmol) 3-(benzo[d][1,3]dioxol-5-
yl)propiolic acid (2h) (380 mg, 2.0 mmol) afforded 3-(benzo[d][1,3]dioxol-5-ylethynyl)-5,5-
dimethylcyclohex-2-enone (3bh) (445 mg, 1.66 mmol, 83% yield ); Yellow solid; mp 101.6-
103.2 oC; 1H NMR (500 MHz, CDCl3) δ 7.03 (dd, J = 8.0 Hz, 1.6 Hz, 1H), 6.92 (d, J = 1.6 Hz,
1H), 6.79 (d, J = 8.1 Hz, 1H), 6.26 (t, J = 1.7 Hz, 1H), 6.00 (s, 2H), 2.41 (d, J = 1.7 Hz, 2H),
2.28 (s, 2H), 1.09 (s, 6H); 13C{1H} NMR (126 MHz, CDCl3) δ 198.9, 148.9, 147.6, 141.3, 130.8,
127.2, 115.1, 111.6, 108.6, 101.5, 99.7, 87.5, 51.0, 44.3, 33.7, 28.1; HRMS (EI-MSES double
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focusing) m/z cacld. for C17H16O3 (M+): 268.1099, found: 268.1101.
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5,5-Dimethyl-3-(naphthalen-1-ylethynyl)cyclohex-2-enone (3bi)
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5,5-Dimethyl-3-oxocyclohex-1-enyl tosylate (1b) (589 mg, 2.0 mmol) 3-(naphthalen-1-
yl)propiolic acid (2i) (392 mg, 2.0 mmol) afforded 5,5-dimethyl-3-(naphthalen-1-
ylethynyl)cyclohex-2-enone (3bi) (444 mg, 1.62 mmol, 81% yield ); Brwon solid; mp 116.4-
118.2 oC; 1H NMR (500 MHz, CDCl3) δ 8.27 (dd, J = 8.5 Hz, 0.8 Hz, 1H), 7.88 (dd, J = 9.3 Hz,
8.5 Hz, 2H), 7.74 (dd, J = 7.2 Hz, 1.2 Hz, 1H), 7.61 (ddd, J = 8.3 Hz, 6.9 Hz, 1.4 Hz, 1H), 7.55
(ddd, J = 8.1 Hz, 6.9 Hz, 1.3 Hz, 1H), 7.46 (dd, J = 8.2 Hz, 7.2 Hz, 1H), 6.43 (t, J = 1.7 Hz, 1H),
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2.5 (d, J = 1.7 Hz, 2H), 2.33 (s, 2H), 1.14 (s, 6H); C{1H} NMR (126 MHz, CDCl3) δ 198.9,
141.1, 133.1, 133.0, 131.3, 131.3, 130.1, 128.4, 127.2, 126.7, 125.7, 125.2, 119.5, 97.5, 93.5,
51.1, 44.4, 33.8, 28.2; HRMS (EI-MSES double focusing) m/z cacld. for C20H18O (M+):
274.1358, found: 274.1359.
3-((4-Chlorophenyl)ethynyl)-5,5-dimethylcyclohex-2-enone (3bk)22
5,5-Dimethyl-3-oxocyclohex-1-enyl tosylate (1b) (589 mg, 2.0 mmol) 3-(4-
chlorophenyl)propiolic acid (2k) (361 mg, 2.0 mmol) afforded 3-((4-chlorophenyl)ethynyl)-5,5-
dimethylcyclohex-2-enone (3bk) (512 mg, 1.98 mmol, 99% yield ); Yellow solid; mp 97.0-98.9
oC; 1H NMR (500 MHz, CDCl3) δ 7.43 (dt, J = 8.6 Hz, 2.1 Hz, 2H), 7.36 (dt, J = 8.6 Hz, 2.1 Hz,
2H), 6.31 (t, J = 1.7 Hz, 1H), 2.44 (d, J = 1.7 Hz, 2H), 2.31 (s, 2H), 1.11 (s, 6H); 13C{1H} NMR
(126 MHz, CDCl3) δ 198.8, 140.7, 135.6, 133.1, 131.6, 128.9, 120.4, 97.9, 89.5, 51.0, 44.2, 33.8,
28.1; MS (EI) m/z = 258 (M+).
4-((5,5-Dimethyl-3-oxocyclohex-1-en-1-yl)ethynyl)benzonitrile (3bm)
5,5-Dimethyl-3-oxocyclohex-1-enyl tosylate (1b) (589 mg, 2.0 mmol) 3-(4-
cyanophenyl)propiolic acid (2m) (342 mg, 2.0 mmol) afforded 4-((5,5-dimethyl-3-oxocyclohex-
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1-en-1-yl)ethynyl)benzonitrile (3bm) (404 mg, 1.62 mmol, 81% yield ); Yellow solid; mp 129.3-
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8
o
1
131.1 C; H NMR (500 MHz, CDCl3) δ 7.67-7.65 (m, 2H), 7.59-7.56 (m, 2H), 6.33 (t, J = 1.7
Hz, 1H), 2.44 (d, J = 1.8 Hz, 2H), 2.31 (s, 2H), 1.11 (s, 6H); 13C{1H} NMR (126 MHz, CDCl3) δ
198.6, 139.8, 132.5, 132.3, 132.1, 126.8, 118.2, 112.7, 96.5, 92.2, 51.0, 44.0, 33.8, 28.1; HRMS
(EI-MSES double focusing) m/z cacld. for C17H15NO (M+): 249.1154, found: 249.1152.
Methyl 4-((5,5-dimethyl-3-oxocyclohex-1-en-1-yl)ethynyl)benzoate (3bp)
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5,5-Dimethyl-3-oxocyclohex-1-enyl tosylate (1b) (589 mg, 2.0 mmol) 3-(4-
(methoxycarbonyl)phenyl)propiolic acid (2p) (408 mg, 2.0 mmol) afforded methyl 4-((5,5-
dimethyl-3-oxocyclohex-1-en-1-yl)ethynyl)benzoate (3bp) (519 mg, 1.84 mmol, 92% yield );
Yellow solid; mp 83.0-85.0 oC; 1H NMR (500 MHz, CDCl3) δ 6.27 (t, J = 1.7 Hz, 2H), 2.49 (td,
J = 6.1 Hz, 1.7 Hz, 4H), 2.46-2.43 (m, 4H), 2.10-2.05 (m, 4H) 1.11 (s, 6H); 13C{1H} NMR (126
MHz, CDCl3) δ 198.3, 141.7, 133.7, 97.0, 37.3, 30.0, 22.5.; MS (EI) m/z cacld. for C18H18O3
(M+): 282.1256, found: 282.1256
3,3'-(Ethyne-1,2-diyl)bis(cyclohex-2-enone) (4)
Oxocyclohex-1-enyl tosylate (1a) (533mg, 2.0 mmol) and propiolic acid (70 mg, 1.0 mmol)
afforded 3,3'-(ethyne-1,2-diyl)bis(cyclohex-2-enone) (5) (128 mg, 0.6 mmol, 60% yield );
1
Yellow oil; H NMR (500 MHz, CDCl3) δ .27 (t, J = 1.7 Hz, 2H), 2.49 (td, J = 6.1 Hz, 1.7 Hz,
4H), 2.46-2.43 (m, 4H), 2.10-2.05 (m, 4H); C{1H} NMR (126 MHz, CDCl3) δ 198.3, 141.7,
13
133.7, 97.0, 37.3, 30.0, 22.5.; HRMS (EI-MSES double focusing) m/z cacld. for C14H14O2 (M+):
214.0996, found: 214.0994.
Acknowledgements
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This research was supported by the National Research Foundation of Korea (NRF) grant funded
by the Korea government (MSIP) (NRF-2012M3A7B4049655, NRF-2015R1A4A1041036). The
spectral data were obtained from the Gwangju center and HRMS data from the Daegu center of
Korea Basic Science Institute.
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Supporting Information
The supporting information is available free of charge on the ACS Publications website at DOI :
1H and 13C NMR spectra of all products.
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