Triflic Acid-Catalyzed Cycloisomerization of 1,6-Enynes: Facile Access to Carbo- And Azaheterocycles

Article abstract of DOI:10.1021/acs.joc.9b03112

A new and efficient strategy for enynes cyclization catalyzed by triflic acid has been described. Various valuable carbocycle-fused and heterocycle-fused ketones were easily accessed by the formation of new C-C and C-O bond under benign reaction condition

Full text of DOI:10.1021/acs.joc.9b03112

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Article
Triflic Acid-Catalyzed Cycloisomerization of 1,6-
enynes: Facile Access to Carbo- and Azaheterocycles
Xiang Liu, Yuhan Wang, Jinlei Zhou, Yue Yu, and Hua Cao
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b03112 • Publication Date (Web): 23 Dec 2019
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Triflic Acid-Catalyzed Cycloisomerization of 1,6-enynes:
Facile Access to Carbo- and Azaheterocycles
8
9
Xiang Liu, Yuhan Wang, Jinlei Zhou, Yue Yu*, and Hua Cao*
School of Chemistry and Chemical Engineering and Guangdong Cosmetics Engineering &
Technology Research Center, Guangdong Pharmaceutical University, Zhongshan 528458, P.R. of
China
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Email: yuyue@gdpu.edu.cn; caohua@gdpu.edu.cn
ABSTRACT: A new and efficient strategy for enynes cyclization catalyzed by triflic
acid has been described. Various valuable carbocycle-fused and heterocycle-fused
ketones were easily accessed by the formation of new C-C and C-O bond under
benign reaction conditions. This protocol also provides another opportunity to
construct polycyclic single-nitrogen ketones via a cation-induced cascade cyclization
of polyenynes. Furthermore, antiviral bioassays revealed that a few compounds
exhibited good antiviral activity against tobacco mosaic virus (TMV) at a
concentration of 200 μg mL-1.
O
R
R1
TfOH (cat.)
TfOH (cat.), H2O
R
R1
R2
6
5/6
activation
C
C
activation
C
C
R
R2
R = 2-thienyl
up to 93% yield
up to 68% yield
Ar
Ar
Me
Me
TfOH
Me
Me
H2O
Me
Me
N
+
multi C
activation
C
Ar
Me
Ts
N
Ts
O
N
Ts
Me
Me
up to 68% yield
INTRODUCTION
The carbocycle-fused and heterocycle-fused ketones are fundamental and ubiquitous
skeletons in biologically active molecules and synthetic pharmaceuticals.1 Considerable
attentions have been devoted to the synthesis of such carbo- and azaheterocycles. Among
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these exquisite protocols, metal-π-acid catalyzed cyclization of enynes by the formation of
new C-C bond have exhibited powerful advantages in building functionalized cyclic
compounds quickly from relatively simple unsaturated substrate (Scheme 1a).2-4 Particularly,
Lewis acidic gold catalysts have been demonstrated to activate the alkyne unit by the manner
of coordination with electrophile-π and a myriad of transformations have been reported in this
approach.5 However, these methods usually need to use expensive even toxic noble metals,
and relative long reaction times. Thus, the development of metal-free strategy for efficient
and direct synthesis of functionalized carbo- and azaheterocycles from enynes is highly
desirable.
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Brønsted acid catalysis has emerged as a powerful tool in modern organic
synthesis.6-9 Its utilization was limited to the formation and cleavage of C−O bonds,
such as hydrolysis and formation of esters and acetals in the early stage.10 In order to
enrich the reaction types, super strong Brønsted acid triflic acid (TfOH) was
developed, which is 100 times stronger than sulfuric acid.11 With the rapidly
development of various super strong acid, the application of Brønsted acids as
catalysts to activate carbonyl, imine, alkene, alkyne, hydroxyl groups have appeared
in the past decades.12 Particularly, Brønsted acids catalysis proved their unique
privilege for the construction of carbo- and heterocycles framework by the formation
of new carbon-carbon bond. For example, the groups of Clark, Balamurugana,
Niggemann, Zhang, and Yamamoto reported acid-catalyzed cycloisomerization
reactions via the activation of isopropen moiety or enones.7,13 Although these seminal
works for the synthesis of cyclic molecules catalyzed by Brønsted acid have been
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documented, it has not been successfully applied to the preparation of six members
carbocycle-fused and heterocycle-fused ketones as well as polycyclic single-nitrogen
ketones. As a continuation of our interest in the synthesis of heterocyclic
compounds,14 we report our discovery that enynes could be selectively activated and
converted to functionated carbo- and azaheterocycles in the presence of catalytic
amount of triflic acid (Scheme 1b).
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Scheme 1. Cycloisomerization of Enynes for the Synthesis of Carbo- and
Azaheterocycles
a. Metal--acid catalyzed cyclization of enynes: Previous work
M
M
R
M
R
R
M (cat.)
X
X
or
R1
R1
R1
R1
b. Triflic acid-catalyzed cycloisomerization of 1,6-enynes: This work
O
R
X
TfOH (cat.), H2O
X
TfOH (cat.)
X
R
R1
R2
5/6
activation
C
activation
C
C
C
R1
Ar
Me
R
R2
R = 2-thienyl
Ar
Me
Me
TfOH
Me
Me
H2O
Me
N
O
+
multi C
C
Ar
Me
Ts
N
activation
N
Me
Ts
Me
Ts
RESULTS AND DISCUSSION
We began our study of cycloisomerization of enynes with compound 1a as the
model substrate. A variety of Lewis acids were first utilized for this cyclization
reaction. When 1a was treated with 10 mol% ZnCl2 catalyst in wet dichloromethane,
none of the desired product was detected after 12 h (Table 1, entry 1). Catalytic
amount of AlCl3 could not initiate the reaction in the same conditons (entry 2). Weak
Brønsted acid acetic acid (AcOH) and trifluoroacetic acid (TFA) were useless to the
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transformation as well (entries 3-4). To our delight, carbocyclic molecule 2a was
formed in 55% yield when using BF3·OEt2 as catalyst (entry 6). In order to increase
the yield, stronger acid trimethylsilyl trifluoromethanesulfonate (TMSOTf) and triflic
acid (TfOH) were tested for the reactions (entries 7 and 8). It was found that TfOH
were more effective leading to 88% yield of 2a, which indicate that the acidity of the
Brønsted acid is vital to this transformation. In fact, the transformation was fast and
the enyne substrate could be nearly converted fully just in 2 h, affording the product
2a in 87% isolated yield (entry 9). Shortening the reaction time to 30 min led to a
slightly decreased yield (entry 10). We then investigated the effects of different
solvents to this cycloisomerization. It appeared that replacing solvent DCM with
Cl(CH2)2Cl delivered 85% yield of desired product (entry 11). And the reaction did
not work well in toluene, which may result from the low solubility of TfOH in toluene
(entry 12). Solvents such as CH3CN, THF, and MeOH gave bad results compared
with CH2Cl2 and no desired cyclic product was observed (entries 13-15). Therefore, in
the presence of 10 mol% TfOH in wet DCM to react for 2 h at room temperature
could afford the product 2a in 87% yield，which were the optimal reaction conditions.
And it should be noted that the stoichiometric amount of H2O for cycloisomerization
reactions with the hydration of alkynes come from wet solvent.
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Table 1. Optimization of Reaction Conditionsa
Ph
O
EtO2C
EtO2C
EtO2C
EtO2C
cat. (10 mol %)
Ph
Me
Me
Solvent, r.t., Time
Me
Me
1a
2a
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entry
cat.
solvent
time
yield (%)b
5
6
7
8
1
2
ZnCl2
AlCl3
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Cl(CH2)2Cl
toluene
CH3CN
THF
12 h
12 h
12 h
12 h
12 h
12 h
12 h
12 h
2 h
nd
nd
9
3
AcOH
TFA
nd
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4
nd
5
MsOH
BF3·OEt2
TMSOTf
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
trace
55
6
7
80
8
88
9
88(87)
82
10
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12
13
14
15
30 min
2 h
85
2 h
22
2 h
nd
2 h
nd
MeOH
2 h
nd
aReaction condition: 1a (0.05 mmol, 1.0 equiv), catalyst (0.005 mmol, 10 mol %), solvent
b
(1.0 mL, 0.05M), r.t.. Refers to NMR yield using benzyl benzoate as the internal standard.
Isolated yield is in the parenthesis in 0.1 mmol scale.
With the optimal conditions in hand, the scope of cycloisomerization of various
enynes catalyzed by triflic acid was evaluated (Scheme 2). Enynes substrates bearing
para- substituent on the phenyl ring could efficiently undergo cycloisomerization to
produce the cyclization products in good yields (e.g. 2b-2f, 76-88%). It proved that
even highly reactive groups such as aldehydes were found to interfere by no means
with the desired reaction approach. The substrate with a chlorine group at the ortho
position on the phenyl ring lead to a slightly drop yield, which may be attributed to
the steric hindrance of the aryl group (2g, 73%). The meta-chlorine group and
dimethyl substituent on the phenyl ring was well-tolerated under the optimized
conditions (2h, 80%; 2i, 85%). Electron-rich naphthyl-substituted enyne could also
proceed the cyclization and give the final product 2j in 68% yield. Substrates 1k-1n
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could convert to the correspounding cyclization products in good yield at the same
conditions. This triflic acid-catalyzed cycloisomerization of enynes not only provide a
direct method to synthesize functionated carbocyclic molecules, but also show a facile
access to azaheterocycles. For example, single-nitrogen enyne was subjected to the
cascade cyclization under the optimal condition, the corresponding azaheterocyclic
product 2o could be afforded in 62% yield. We were delighted to find that the
electron-rich 3-thiophenyl on the enyne was also tolerated under the strong acidity
conditions (2p, 62%). Furthermore, the effect of electron density of aryl group on
enyne was studied. It was found that trifluoromethyl and methoxy group installed at
the para positions of the phenyl ring could smoothly undergo the cyclization to
deliver the corresponding azaheterocyclic products (2q, 70%; 2r, 63%). Based on
these results, our method provides an efficient and direct pathway for the activate
double bonds and achieves the carbon-carbon bond and carbon-oxygen bond
formation in one step.
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Scheme 2. Substrate Scope of Cycloisomerizationa
O
R
X
TfOH (10 mol %)
CH2Cl2, r.t., 2 h
X
R
Me
Me
Me
2
Me
1
O
O
Cl
, R1 = Me, 85%
2b
EtO2C
EtO2C
EtO2C
EtO2C
, R1 = F, 88%
2c
, R1 = Cl, 83%
2d
R1
Me
Me
, R1 = CHO, 76%
2e
2f
Me
Me
, R1 = CO2Me, 80%
2g
, 73%
O
O
EtO2C
EtO2C
EtO2C
EtO2C
Cl
Me
Me
Me
Me
O
Me
Me
2i
2h
, 80%
, 85
O
O
MeO
MeO
EtO2C
EtO2C
AcO
AcO
Ph
Me
Ph
Me
Me
Me
, 93%
O
Me
Me
, 87%
2k
2j
, 68%
O
2l
O
MeO2C
MeO2C
PhO2S
PhO2S
Ph
Me
Ph
Me
Me
TsN
Ph
Me
Me
Me
2m
2n
, 84%
, 89%
2o
,62%
O
O
O
TsN
TsN
TsN
OMe
S
Me
Me
2p
Me
Me
2q
Me
Me
CF3
, 70%
, 62%
2r
, 63%
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aConditions: 1 (0.1 mmol, 1.0 equiv), TfOH (0.9 μL, 0.01 mmol, 10 mol %), CH2Cl2 (2.0
mL, 0.05M), r.t., 2 h. Isolated yield.
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In additon, the method could also be applied to prepare five members
azaheterocycle-fused ketones by adjusting to operate the enynes containing a
1,1-disubstituent alkene under the same conditons. We executed the cyclization using
enynes 3 as the substrate, five members azaheterocycle-fused ketones 4 could be
generated in good yields (Scheme 3). For example, desired product 4a was formed
in the presence of 10 mol% TfOH in 71% yield. When the electron-withdrawing
group such as –Cl and –Br was put on the phenyl ring of substrates (3b and 3c), the
cyclization also proceeded to give the corresponding products with a slightly decrease
of isolated yield. Pleasingly, this method was also suitable for the alkene furnished an
aryl substitutent affording the desired product 4d in 61% yield. From the above
results, it was concluded that the catalytic system was applicable to both five and six
members azaheterocycle compounds.
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Scheme 3. Cycloisomerization of 1,6-enynesa
O
Ar
TfOH (10 mol %)
TsN
Ar
TsN
CH2Cl2, r.t., 2 h
R
Me
4
R
3
O
O
O
Cl
Ph
TsN
TsN
TsN
Me
Me
Me
Me
4c
, 64%
Ph
R1
Me
4d
1
1
, 61%
4a
4b
, R = H, 71%; , R = F, 66%
aConditions: 3 (0.1 mmol, 1.0 equiv), TfOH (0.9 μL, 0.01 mmol, 10 mol %), CH2Cl2 (2.0 mL,
0.05M), r.t., 2 h. Isolated yield.
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As we all known that the noble metals could serve as π-acid and exhibit powerful
ability for carban-carban triple bonds activation, and a wide range of derived new
reaction has been discovered. In contrast, the Brønsted acid catalysis usually preferred
to activate carban-carban double bond in enynes to generate carbocation, which could
be attacked by various nucleophiles. Interestingly, when the enyne 5 with an
electron-rich 2-thiophenyl was employed to this transformation, a new cyclization
product 6 was obtained in 68% yield (eq. 1). Owing to the subtle difference of
electron property on unsaturated bonds between substrate 5 and 1p, different
cyclization products could be produced in the presence of catalytic amount of triflic
acid. The substrate 7 was also performed under the optimized conditons, lactonisation
product 8 was detected in 80% yield but no cycloisomerization product formed (eq.
2). To confirm reaction efficiency, we carried out gram-scale reaction using enyne 1a
as the substrate in the presence of 10 mol% catalyst TfOH. The carbocyclic product
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could still be obtained in 83% yield (eq. 3).
S
TsN
Me
S
TfOH (10 mol %)
CH2Cl2, r.t., 2 h
TsN
(1)
(2)
Me
Me
5
6
, 68% yield
EtO2C
O
Ph
Ph
Ph
EtO2C
EtO2C
TfOH (10 mol %)
CH2Cl2, r.t., 2 h
O
7
8
, 80% yield
O
EtO2C
EtO2C
EtO2C
EtO2C
TfOH (10 mol %)
CH2Cl2, r.t., 2 h
(3)
Ph
Me
Me
, 1.05 g, 83% yield
Me
Me
, 1.19 g
2a
1a
To extend this method to more challenging substrates, polyenynes was examined.
To our delight, numbers of polycyclic single-nitrogen ketones could be synthesized
via a cation-induced cascade cyclization of polyenynes in good yields (Scheme 4).
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Substrate 9a underwent cascade cyclization to afford product 10a in 66% yield. This
method has good functional tolerance as well. A variety of substituents, such as 4-Me,
4-CO2Me, and 4-F, on the phenyl ring of polyenyne were worked well under the same
acid-catalyzed conditions and gave the corresponding polycyclic single-nitrogen
ketones (10b-d, 63-68%). The structure of 10b was also confirmed by X-ray crystal
structure analysis (see the Supporting Information (SI)).
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Scheme 4. Triflic Acid-Catalyzed Cascade Cyclizationa
Me Me
Ar
TfOH (10 mol %)
TsN
O
TsN
CH2Cl2, r.t., 2 h
Me
Me
Me
Me
Ar
10
9
Me Me
Me
Me Me
Me Me
Me Me
TsN
TsN
TsN
O
TsN
O
Me
Me
Me
Ph
O
O
CH3
F
CO2Me
10a
, 66%
10b
, 68%
10c
, 64%
10d
, 63%
aConditions: 9 (0.1 mmol, 1.0 equiv), TfOH (0.9 μL, 0.01 mmol, 10 mol %), CH2Cl2 (2.0 mL,
0.05M), r.t., 2 h. Isolated yield.
In order to test the antiviral activity of the compound synthesized by this method,
we conducted bioassays against tobacco mosaic virus (TMV) at a concentration of
200 μg mL-1. These data are summarized in Table 2 and Figure 1. The results
indicated that 10a showed a good therapeutic effect on TMV, the percentage
inhibition was 54.2%, which even exceeded that of ningnanmycin (48.5%). The above
biological activity study results demonstrate that the polycyclic single-nitrogen
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derivative has good biocontrol activity, though the detail effect on TMV of the
molecule structure need to be further studied.
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Table 2. Antiviral activities of the target compounds against TMVa
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percentage toxic regression
EC50
(μg mL-1)
compound
10a
R
inhibition
equation
Y=0.8122X +
3.2188
54.2%
0.9918
0.9958
155.99
278.23
Y=1.0717X +
2.3804
2c
45.2%
Y=1.4216X +
1.3442
2r
32.1%
48.5%
0.9933
--
372.93
--
Ningnanmycin
--
aConditions: Tested and calculated at the drug test concentrations of 200 μg mL-1. The data
are average of three replicates. Agents ningnanmycin is commercial.
Figure 1. The test of antiviral activity against TMV
Right half leaves treated with the solution of 10a
A plausible mechanism that is consistent with the experimental results mentioned
above is proposed in Scheme 5. Protonation of the terminal trisubstituent alkene
moiety in the presence of triflic acid leads to the relative stable carbocation I. Active
carbocation I was attacked by another intramolecular nucleophilic group trisubstituent
alkene, meanwhile the cationic cascade process is terminated by intermolecular H2O
capture to afford the intermediate Ⅲ. Then, enol intermediate Ⅳ was formed after a
proton loss. Subsquently, enol isomerisation of Ⅳ to give fanal product.
Scheme 5. Possible Mechanism.
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Ph
Ph
Ph
4
5
6
7
8
9
H
+
2O
Me
Me
Me
+
H+
Me
Me
Me
Me
N
N
N
+
Me
Me
Ts
Ts
Ph
Ts
II
9a
I
Ph
Me
Me
Me
Me
- H+
Me
OH
Me
OH2
N
O
N
N
Ph
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10a
IV
III
In summary, we have developed an efficient and straightforward triflic acid
catalysis system to synthesize a variety of carbocycle-fused and heterocycle-fused
ketones under mild reaction conditions. This catalytic reaction proceeds in a broad
scope and good functional group tolerance, and can be easily scaled up. In addition,
this method was also successfully applied to construct polycyclic single-nitrogen
ketones via a cation-induced cascade cyclization of polyenynes. Antiviral bioassays
revealed that compound 10a exhibited good antiviral activity against TMV at a
concentration of 200 μg mL-1. A further investigation of potential bioactivity of these
carbons and azaheterocyclic molecules are ongoing in our laboratory.
EXPERIMENTAL SECTION
General Methods
Unless otherwise noted, commercial reagents were purchased from Macklin,
Energy, Aladdin, Adamas and so on. The solvents used in the reaction, such as
dichloromethane, THF, and so on, are all analytical pure, and their water content is
0.03% - 0.05%. All reactions were carried out using oven-dried glassware and all
catalytic reactions proceeded without special care. Analytical thin layer
chromatography was carried out using silica gel GF254, and visualized under 254 nm
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UV light or by staining with potassium permanganate. Column chromatography was
performed on 200-300 mesh silica gel (Huanghai, China).
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9
19
13
1H, F and C{1H} NMR spectra were recorded on an Bruker Ascend 400MHz
spectrometer at ambient temperature. 1H NMR spectra are referred to the TMS signal
(δ = 0 ppm) and 13C NMR spectra are referred to the residual solvent signal (δ = 77.16
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1
ppm). Data for H NMR are reported as follows: chemical shifts (δ ppm),
multiplicities (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br =
broad), coupling constants (Hz), integration. Data for 13C{1H} NMR and 19F NMR are
reported as follows: chemical shift (δ ppm), multiplicity (q = quartet), coupling
constant (Hz).
Preparation of enyne substrates: The procedure for the synthesis of enyne
substrates was based on the known procedure.15a Compounds 1b, 1f-1j, 1p, 1r, and 9
are new and their characterization data are as follows. Other starting compounds are
known and their spectral data are in accordance with those reported in the literature.15
Diethyl 2-(3-methylbut-2-en-1-yl)-2-(3-(p-tolyl)prop-2-yn-1-yl)malonate (1b):
Colorless oil. IR (KBr): 2984, 2930, 1731, 1471, 1223, 1195, 660 cm-1. 1H NMR (400
MHz, CDCl3) δ 7.25 (d, 2H), 7.06 (d, J = 7.9 Hz, 2H), 4.97 (ddd, J = 7.6, 4.4, 1.3 Hz,
1H), 4.26 – 4.15 (m, 4H), 2.97 (s, 2H), 2.83 (d, J = 8.4 Hz, 2H), 2.31 (s, 3H), 1.71 (s,
13
3H), 1.68 (s, 3H), 1.25 (t, 6H). C {1H} NMR (101 MHz, CDCl3) δ 170.3, 137.9,
136.5, 131.5, 129.0, 120.4, 117.5, 84.2, 83.3, 61.5, 57.4, 30.9, 26.1, 26.1, 23.4, 21.4,
18.1, 14.1. HR-MALDI-MS m/z calcd. for C22H28NaO4 [M+Na]+: 379.1880, found:
379.1879.
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2-(3-(4-(methoxycarbonyl)phenyl)prop-2-yn-1-yl)-2-(3-methylbut-2-en-1-yl)malo
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nate (1f):
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1
Colorless oil. IR (KBr): 2984, 2925, 1727, 1440, 1278, 1175, 1108 cm-1. H NMR
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(400 MHz, CDCl3) δ 7.95 (d, J = 8.2 Hz, 2H), 7.42 (d, J = 8.2 Hz, 2H), 4.97 (t, J = 7.7
Hz, 1H), 4.32 – 4.14 (m, 4H), 3.91 (s, 3H), 3.02 (s, 2H), 2.84 (d, J = 7.6 Hz, 2H), 1.72
(s, 3H), 1.69 (s, 3H), 1.27 (t, J = 7.1 Hz, 6H). 13C {1H} NMR (101 MHz, CDCl3) δ
170.2, 166.7, 136.8, 131.6, 129.5, 129.3, 128.2, 117.3, 88.6, 82.7, 61.7, 57.4, 52.3,
31.0, 26.2, 23.5, 18.1, 14.2. HR-MALDI-MS m/z calcd. for C23H28NaO6 [M+Na]+:
423.1778, found: 423.1771.
Diethyl 2-(3-(2-chlorophenyl)prop-2-yn-1-yl)-2-(3-methylbut-2-en-1-yl)malonate
(1g):
1
Colorless oil. IR (KBr): 2984, 2925, 1731, 1471, 1223, 1195, 1061 cm-1. H NMR
(400 MHz, CDCl3) δ 7.37 (ddd, J = 16.7, 7.4, 1.4 Hz, 2H), 7.23 – 7.10 (m, 2H), 5.04 –
4.92 (m, 1H), 4.31 – 4.11 (m, 4H), 3.06 (s, 2H), 2.87 (d, J = 7.7 Hz, 2H), 1.70 (d, J =
11.8 Hz, 6H), 1.26 (t, J = 7.1 Hz, 6H). 13C {1H} NMR (101 MHz, CDCl3) δ 170.2,
136.8, 135.9, 133.6, 129.2, 129.0, 126.4, 123.3, 117.4, 90.7, 80.1, 61.7, 57.5, 30.9,
26.2, 23.7, 18.2, 14.2. HR-MALDI-MS m/z calcd. for C21H25ClNaO4 [M+Na]+:
399.1334, found: 399.1332.
Diethyl 2-(3-(3-chlorophenyl)prop-2-yn-1-yl)-2-(3-methylbut-2-en-1-yl)malonate
(1h):
1
Colorless oil. IR (KBr): 2984, 2933, 1735, 1451, 1294, 1195, 1057 cm-1. H NMR
(400 MHz, CDCl3) δ 7.33 (s, 1H), 7.28 – 7.16 (m, 3H), 5.02 – 4.86 (m, 1H), 4.32 –
4.14 (m, 4H), 2.98 (s, 2H), 2.82 (d, J = 7.7 Hz, 2H), 1.72 (s, 3H), 1.68 (s, 3H), 1.26
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(tt, J = 6.5, 3.2 Hz, 6H). 13C {1H} NMR (101 MHz, CDCl3) δ 170.2, 136.8, 134.1,
131.5, 129.89, 129.5, 128.5, 128.3, 125.1, 117.3, 86.6, 82.0, 61.7, 57.4, 30.9, 26.2,
23.4, 18.1, 14.2. HR-MALDI-MS m/z calcd. for C21H25ClNaO4 [M+Na]+: 399.1334,
found: 399.1331.
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Diethyl
2-(3-(3,4-dimethylphenyl)prop-2-yn-1-yl)-2-(3-methylbut-2-en-1-yl)malonate (1i):
Colorless oil. IR (KBr): 2930, 1737, 1461, 1223, 1195, 766, 657 cm-1. 1H NMR (400
MHz, CDCl3) δ 7.16 – 7.06 (m, 1H), 7.05 – 6.96 (m, 1H), 6.92 – 6.79 (m, 1H), 4.92 –
4.80 (m, 1H), 4.20 – 4.07 (m, 4H), 2.93 (s, 2H), 2.74 (d, J = 7.7 Hz, 2H), 1.63 (s, 3H),
13
1.62 (s, 3H), 1.19 (t, J = 7.1 Hz, 6H). C {1H} NMR (101 MHz, CDCl3) δ 170.2,
136.8, 131.6, 126.9, 126.5, 123.5, 117.4, 89.2, 76.4, 61.7, 57.4, 31.0, 26.2, 23.8, 18.2,
14.2. HR-MALDI-MS m/z calcd. for C23H30NaO4 [M+Na]+: 393.2036, found:
393.2036.
Diethyl 2-(3-methylbut-2-en-1-yl)-2-(3-(naphthalen-1-yl)prop-2-yn-1-yl)malonate
(1j):
Colorless oil. IR (KBr): 2930, 1731, 1471, 1223, 1195, 765, 660 cm-1. 1H NMR (400
MHz, CDCl3) δ 8.29 (d, J = 8.3 Hz, 1H), 7.85 – 7.75 (m, 2H), 7.60 (d, J = 7.1 Hz,
1H), 7.58 – 7.52 (m, 1H), 7.49 (ddd, J = 8.1, 6.9, 1.3 Hz, 1H), 7.38 (dt, J = 8.2, 5.6
Hz, 1H), 5.03 (t, J = 8.3, 7.0 Hz, 1H), 4.30 – 4.19 (m, 4H), 3.16 (s, 2H), 2.93 (d, J =
7.6 Hz, 2H), 1.73 (s, 3H), 1.69 (s, 3H), 1.27 (t, J = 7.1 Hz, 6H). 13C {1H} NMR (101
MHz, CDCl3) δ 170.4, 136.8, 133.5, 133.2, 130.5, 128.4, 128.3, 126.7, 126.4, 126.4,
125.3, 121.2, 117.5, 90.0, 81.4, 61.7, 57.6, 31.1, 26.2, 23.9, 18.2, 14.2.
HR-MALDI-MS m/z calcd. for C25H28NaO4 [M+Na]+: 415.1880, found: 415.1881.
4-Methyl-N-(3-methylbut-2-en-1-yl)-N-(3-(thiophen-3-yl)prop-2-yn-1-yl)benzenes
ulfonamide (1p):
White solid. mp: 84.4–85.0 °C. IR (KBr): 3114, 2921, 1345, 1164, 1089, 903 cm-1. 1H
NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.3 Hz, 2H), 7.28 (d, J = 8.0 Hz, 2H), 7.21
(dt, J = 8.4, 4.2 Hz, 1H), 7.13 (dd, J = 3.0, 1.0 Hz, 1H), 6.79 (dd, J = 5.0, 1.1 Hz, 1H),
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5.26 – 5.12 (m, 1H), 4.27 (s, 2H), 3.88 (d, J = 7.3 Hz, 2H), 2.37 (s, 3H), 1.76 (s, 3H),
1.71 (s, 3H). 13C {1H} NMR (101 MHz, CDCl3) δ 143.4, 139.2, 136.1, 129.6, 129.5,
128.8, 128.0, 125.3, 121.5, 118.1, 81.1, 80.6, 44.2, 36.4, 26.0, 21.6, 18.0.
HR-MALDI-MS m/z calcd. for C19H21NNaO2S2 [M+Na]+: 382.0906, found:
382.0900.
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4-Methyl-N-(3-methylbut-2-en-1-yl)-N-(3-(4-(trifluoromethyl)phenyl)prop-2-yn-1
-yl)benzenesulfonamide (1r):
White solid. mp: 65.1–65.7 °C. IR (KBr): 2976, 2925, 1617, 1325, 1160, 1120, 655
1
cm-1. H NMR (400 MHz, CDCl3) δ 7.84 – 7.73 (m, 2H), 7.53 (t, J = 7.6 Hz, 2H),
7.34 – 7.22 (m, 2H), 7.17 (d, J = 8.0 Hz, 2H), 5.19 (dddd, J = 7.3, 6.0, 2.7, 1.4 Hz,
1H), 4.31 (s, 2H), 3.90 (d, J = 7.3 Hz, 2H), 2.35 (s, 3H), 1.77 (s, 3H), 1.71 (s, 3H). 13C
{1H} NMR (101 MHz, CDCl3) δ 143.5, 139.4, 136.1, 131.8, 130.1, 129.6, 128.0,
126.5 (q, J = 263.2 Hz), 126.2 (q, J = 1.4 Hz), 125.25 (q, J = 3.9 Hz), 117.98, 85.14,
84.12, 44.39, 36.33, 26.06, 21.53, 18.04. 19F NMR (377 MHz, CDCl3) δ -62.91.
HR-MALDI-MS m/z calcd. for C22H22F3NNaO2S [M+Na]+: 444.1216, found:
444.1215.
(E)-N-(3,7-Dimethylocta-2,6-dien-1-yl)-4-methyl-N-(3-phenylprop-2-yn-1-yl)benz
enesulfonamide (9a):
White solid. 539.6 mg, 64% total yield. mp: 74.2–75.1 °C. IR (KBr): 2930, 2900,
1
1634, 1465, 910, 766, 660 cm-1. H NMR (400 MHz, CDCl3) δ 7.77 (t, J = 7.1 Hz,
2H), 7.32 – 7.18 (m, 5H), 7.08 – 6.99 (m, 2H), 5.20 – 5.13 (m, 1H), 5.09 – 5.00 (m,
1H), 4.28 (s, 2H), 3.89 (d, J = 7.3 Hz, 2H), 2.32 (s, 3H), 2.04 (ddd, J = 18.0, 14.7, 4.7
13
Hz, 4H), 1.68 (s, 6H), 1.59 (s, 3H). C {1H} NMR (101 MHz, CDCl3) δ 143.4,
142.6, 136.1, 132.0, 131.5, 129.5, 128.4, 128.2, 128.0, 123.9, 122.4, 118.0, 85. 5,
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82.3, 44.2, 39.8, 36.2, 26.3, 25.8, 21.5, 17.8, 16.3. HR-MALDI-MS m/z calcd. for
C26H31NNaO2S [M+Na]+: 444.1968, found: 444.1959.
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(E)-N-(3,7-Dimethylocta-2,6-dien-1-yl)-4-methyl-N-(3-(p-tolyl)prop-2-yn-1-yl)ben
zenesulfonamide (9b):
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White solid. 548.9 mg, 63% total yield. mp: 75.9–76.2 °C. IR (KBr): 2927, 2908,
1
1465, 1330, 1155, 911, 759 cm-1. H NMR (400 MHz, CDCl3) δ 7.69 (d, J = 8.3 Hz,
2H), 7.19 – 7.13 (m, 2H), 6.95 (d, J = 7.9 Hz, 2H), 6.85 (d, J = 8.1 Hz, 2H), 5.07 (td,
J = 7.2, 1.0 Hz, 1H), 4.96 (ddd, J = 6.7, 5.4, 1.2 Hz, 1H), 4.19 (s, 2H), 3.81 (d, J = 7.3
Hz, 2H), 2.24 (d, J = 6.3 Hz, 6H), 2.08 – 1.92 (m, 4H), 1.59 (s, 6H), 1.51 (s, 3H). 13C
{1H} NMR (101 MHz, CDCl3) δ 143.3, 142.5, 138.5, 136.1, 131.9, 131.4, 129.5,
128.9, 127.9, 123.9, 119.4, 118.1, 85. 6, 81.6, 44.1, 39.7, 36.3, 26.4, 25.8, 21.5, 17.8,
16.3. HR-MALDI-MS m/z calcd. for C27H33NNaO2S [M+Na]+: 458.2124, found:
458.2124.
4-(3-(N-(3,7-dimethylocta-2,6-dien-1-yl)-4-methylphenylsulfonamido)prop-1-yn-1
-yl)benzoate (9c):
White solid. 565.9 mg, 59% total yield. mp: 87.3–88.9 °C. IR (KBr): 2913, 1600,
1515, 1327, 1150, 913, 845, 647 cm-1. 1H NMR (400 MHz, CDCl3) δ 7.95 – 7.88 (m,
2H), 7.77 (d, J = 8.3 Hz, 2H), 7.27 – 7.22 (m, 2H), 7.13 – 7.05 (m, 2H), 5.18 – 5.12
(m, 1H), 5.08 – 4.99 (m, 1H), 4.29 (s, 2H), 3.92 (s, 3H), 3.89 (d, J = 7.3 Hz, 2H), 2.33
(s, 3H), 2.11 – 2.02 (m, 4H), 1.68 (s, 3H), 1.67 (s, 3H), 1.59 (s, 3H). 13C {1H} NMR
(101 MHz, CDCl3) δ 166.5, 143.6, 142.8, 136.1, 132.1, 131.4, 129.6, 129.4, 128.0,
127.8, 127.1, 123.8, 117. 9, 85.6, 84.7, 52.4, 44.3, 39.8, 36.2, 26.3, 25.9, 21.6, 17.8,
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16.3, 16.3. HR-MALDI-MS m/z calcd. for C28H33NNaO4S [M+Na]+: 502.2023,
found: 502.2022.
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(E)-N-(3,7-Dimethylocta-2,6-dien-1-yl)-N-(3-(4-fluorophenyl)prop-2-yn-1-yl)-4-m
ethylbenzenesulfonamide (9d):
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White solid. 526.8 mg, 60% total yield. mp: 71.3–71.9 °C. IR (KBr): 2910, 2855,
1
1515, 1330, 1155, 843, 650 cm-1. H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.3 Hz,
2H), 7.25 (t, J = 6.5 Hz, 2H), 7.07 – 6.98 (m, 2H), 6.98 – 6.86 (m, 2H), 5.15 (td, J =
7.3, 1.0 Hz, 1H), 5.04 (td, J = 5.4, 2.6 Hz, 1H), 4.26 (s, 2H), 3.88 (dj, J = 8.2 Hz, 2H),
2.33 (s, 3H), 2.11 – 2.01 (m, 4H), 1.68 (s, 6H), 1.59 (s, 3H). 13C {1H} NMR (101
MHz, CDCl3) δ 162.5 (d, J = 249.8 Hz), 143.4, 142.6, 136.2, 133.4 (d, J = 8.4 Hz),
132.0, 129.5, 128.0, 123.8, 118.5 (d, J = 3.5 Hz), 118.0, 118.5 (d, J = 3.5 Hz), 84.3,
82.1, 82.1, 44.2, 39.7, 36.2, 26.2, 25.8, 21.5, 17.8, 16.3. 19F NMR (377 MHz, CDCl3)
δ -110.63. HR-MALDI-MS m/z calcd. for C26H30FNNaO2S [M+Na]+: 462.1874,
found: 462.1873.
(E)-Methyl
General procedure for triflic acid-catalyzed cyclization of enynes: To a solution of
enyne substrate (0.1 mmol, 1.0 equiv) in wet CH2Cl2 (2 mL, 0.05M) at room
temperature was added TfOH (0.9 μL, 0.01 mmol, 0.1 equiv). The resultant mixture
was stirred at room temperature for 2 h. Next the mixture was concentrated in vacuo
and purified by preparative TLC (eluent: PE/EtOAc = 10/1, v/v) to yield the
corresponding cyclization product.
Diethyl 3-benzoyl-4,4-dimethylcyclohexane-1,1-dicarboxylate (2a):
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Colorless oil. 31.4 mg, 87% yield. IR (KBr): 2925, 2846, 1731, 1522, 1239, 545 cm-1.
1H NMR (400 MHz, CDCl3) δ 7.91 (dd, J = 5.2, 3.3 Hz, 2H), 7.51 – 7.43 (m, 1H),
7.43 – 7.34 (m, 2H), 4.28 – 4.15 (m, 2H), 4.12 – 4.03 (m, 2H), 3.61 (dd, J = 12.7, 3.3
Hz, 1H), 2.24 – 2.11 (m, 2H), 2.09 – 1.96 (m, 2H), 1.39 – 1.29 (m, 2H), 1.22 (t, 3H),
1.15 (t, J = 7.1 Hz, 3H), 1.00 (s, 3H), 0.75 (s, 3H). 13C {1H} NMR (101 MHz, CDCl3)
δ 203.3, 171.9, 171.5, 138.9, 133.0, 128.7, 128.3, 61.6, 61.5, 54.8, 48. 6, 38.7, 33.3,
31.3, 30.2, 26.8, 20.3, 14.3, 14.2. HR-MALDI-MS m/z calcd. for C21H28NaO5
[M+Na]+: 383.1829, found: 383.1822.
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Diethyl 4,4-dimethyl-3-(4-methylbenzoyl)cyclohexane-1,1-dicarboxylate (2b):
Colorless oil. 31.8 mg, 85% yield. IR (KBr): 3460, 2961, 2929, 2862, 1727, 1672,
1243 cm-1. 1H NMR (400 MHz, CDCl3) δ 7.89 (d, J = 8.2 Hz, 2H), 7.26 (d, J = 9.6 Hz,
2H), 4.36 – 4.22 (m, 2H), 4.20 – 4.08 (m, 2H), 3.64 (dd, J = 12.6, 3.3 Hz, 1H), 2.41 (s,
3H), 2.24 (ddd, J = 16.5, 5.5, 2.4 Hz, 2H), 2.15 – 2.04 (m, 2H), 1.46 – 1.35 (m, 2H),
1.30 (t, J = 7.1 Hz, 3H), 1.22 (t, J = 7.1 Hz, 3H), 1.06 (s, 3H), 0.82 (s, 3H). 13C {1H}
NMR (101 MHz, CDCl3) δ 202.8, 171.9, 171.5, 143.7, 136.4, 129.4, 128.5, 61.6, 61.
5, 54.8, 48.3, 38.7, 33.2, 31.3, 30.2, 26.8, 21.7, 20.3, 14.3, 14.1. HR-MALDI-MS m/z
calcd. for C22H30NaO5 [M+Na]+: 397.1985, found: 397.1989
Diethyl 3-(4-fluorobenzoyl)-4,4-dimethylcyclohexane-1,1-dicarboxylate (2c):
Colorless oil. 33.3 mg, 88% yield. IR (KBr): 2972, 2933, 1731, 1684, 1589, 1227,
1156 cm-1. 1H NMR (400 MHz, CDCl3) δ 8.01 – 7.90 (m, 2H), 7.09 – 7.00 (m, 2H),
4.29 – 4.15 (m, 2H), 4.14 – 4.02 (m, 2H), 3.57 (dd, J = 12.7, 3.3 Hz, 1H), 2.23 – 2.10
(m, 2H), 2.09 – 1.96 (m, 2H), 1.40 – 1.26 (m, 2H), 1.22 (t, 3H), 1.15 (t, J = 7.1 Hz,
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3H), 1.00 (s, 3H), 0.76 (s, 3H). 13C {1H} NMR (101 MHz, CDCl3) δ 201. 7, 171.8,
171.5, 165.8 (d, J = 254.5 Hz), 135.2 (d, J = 2.9 Hz), 131. 0 (d, J = 9.3 Hz), 115. 8 (d,
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J = 21.8 Hz), 61.7, 61.5, 54.8, 48.5, 38.7, 33.3, 31.2, 30.3, 26.7, 20.2, 14.3, 14.2. F
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NMR (377 MHz, CDCl3) δ -105.84. HR-MALDI-MS m/z calcd. for C21H27FNaO5
[M+Na]+: 401.1735, found: 401.1731.
Diethyl 3-(4-chlorobenzoyl)-4,4-dimethylcyclohexane-1,1-dicarboxylate (2d):
Colorless oil. 32.8 g, 83% yield. IR (KBr): 2968, 1735, 1684, 1589, 1250, 1093, 848
cm-1. 1H NMR (400 MHz, CDCl3) δ 7.98 – 7.90 (m, 2H), 7.47 – 7.39 (m, 2H), 4.35 –
4.21 (m, 2H), 4.21 – 4.10 (m, 2H), 3.63 (dd, J = 12.7, 3.3 Hz, 1H), 2.24 (ddt, J = 14.1,
9.3, 2.9 Hz, 2H), 2.14 – 2.03 (m, 2H), 1.46 – 1.34 (m, 2H), 1.30 (t, J = 7.1 Hz, 3H),
1.22 (t, J = 7.1 Hz, 3H), 1.06 (s, 3H), 0.82 (s, 3H). 13C {1H} NMR (101 MHz, CDCl3)
δ 202.1, 171.8, 171.5, 139.4, 137.1, 129.7, 129.0, 61.7, 61.5, 54.7, 48.6, 38.6, 33.3,
31.2, 30.2, 26.7, 20.2, 14.3, 14.1. HR-MALDI-MS m/z calcd. for C21H27ClNaO5
[M+Na]+: 417.1439, found: 417.1434.
Diethyl 3-(4-formylbenzoyl)-4,4-dimethylcyclohexane-1,1-dicarboxylate (2e):
Colorless oil. 29.5 mg, 76% yield. IR (KBr): 2980, 1727, 1290, 1250, 1160, 1045,
864 cm-1. 1H NMR (400 MHz, CDCl3) δ 10.11 (s, 1H), 8.13 (d, J = 8.2 Hz, 2H), 7.98
(d, J = 8.2 Hz, 2H), 4.38 – 4.23 (m, 2H), 4.23 – 4.10 (m, 2H), 3.71 (dd, J = 12.7, 3.2
Hz, 1H), 2.34 – 2.19 (m, 2H), 2.16 – 2.04 (m, 2H), 1.48 – 1.35 (m, 2H), 1.31 (t, J =
7.1 Hz, 3H), 1.24 (t, J = 12.1, 5.0 Hz, 3H), 1.07 (s, 3H), 0.82 (s, 3H). 13C {1H} NMR
(101 MHz, CDCl3) δ 203.0, 191.8, 171.7, 171.5, 143.3, 138.9, 130.0, 128.8, 61.8,
61.6, 54.7, 49.4, 38.6, 33.4, 31.3, 30.1, 26.7, 20.2, 14.3, 14.2. HR-MALDI-MS m/z
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calcd. for C22H28NaO6 [M+Na]+: 411.1778, found: 411.1773.
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3-(4-(methoxycarbonyl)benzoyl)-4,4-dimethylcyclohexane-1,1-dicarboxylate (2f):
Colorless oil. 33.5 mg, 80% yield. IR (KBr): 2956, 2862, 1731, 1684, 1282, 1246,
1160 cm-1. 1H NMR (400 MHz, CDCl3) δ 8.05 (d, 2H), 7.96 (d, 2H), 4.29 – 4.16 (m,
2H), 4.14 – 4.04 (m, 2H), 3.88 (s, 3H), 3.61 (dd, J = 12.7, 3.3 Hz, 1H), 2.27 – 2.12 (m,
2H), 2.09 – 1.97 (m, 2H), 1.39 – 1.28 (m, 2H), 1.23 (t, J = 8.5, 5.7 Hz, 3H), 1.14 (t, J
= 7.1 Hz, 3H), 0.99 (s, 3H), 0.74 (s, 3H). 13C {1H} NMR (101 MHz, CDCl3) δ 203.0,
171.8, 171.4, 166.4, 142.2, 133.7, 130.0, 128.2, 61.7, 61.6, 54.7, 52. 6, 49.2, 38.6,
33.3, 31.3, 30.1, 26.7, 20.2, 14.3, 14.1. HR-MALDI-MS m/z calcd. for C23H30NaO7
[M+Na]+: 441.1884, found: 441.1875.
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Diethyl 3-(2-chlorobenzoyl)-4,4-dimethylcyclohexane-1,1-dicarboxylate (2g):
Colorless oil. 28.8 mg, 73% yield. IR (KBr): 2972, 2870, 1735, 1680, 1570, 1467,
1049 cm-1. 1H NMR (400 MHz, CDCl3) δ 7.49 (dd, J = 7.4, 1.8 Hz, 1H), 7.40 (dd, J =
7.8, 1.5 Hz, 1H), 7.38 – 7.29 (m, 2H), 4.29 – 4.21 (m, 2H), 4.21 – 4.13 (m, 2H), 3.49
(dd, J = 12.8, 3.3 Hz, 1H), 2.42 – 2.33 (m, 1H), 2.24 – 2.15 (m, 2H), 2.06 – 1.93 (m,
1H), 1.41 – 1.34 (m, 2H), 1.31 – 1.21 (m, 6H), 1.04 (s, 3H), 0.83 (s, 3H). 13C {1H}
NMR (101 MHz, CDCl3) δ 205.4, 172.0, 171.2, 141.5, 131.6, 130.9, 130.8, 129.1,
126.9, 61. 7, 61.5, 54.7, 53.7, 38.7, 33.8, 31.1, 29.4, 26.7, 20.3, 14.2, 14.2.
HR-MALDI-MS m/z calcd. for C21H27ClNaO5 [M+Na]+: 417.1439, found: 417.1433.
Diethyl 3-(3-chlorobenzoyl)-4,4-dimethylcyclohexane-1,1-dicarboxylate (2h):
Colorless oil. 31.6 mg, 80% yield. IR (KBr): 2980, 1727, 1688, 1471, 1243, 1156,
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758 cm-1. 1H NMR (400 MHz, CDCl3) δ 7.93 (t, J = 1.8 Hz, 1H), 7.88 (d, J = 7.8 Hz,
1H), 7.53 (ddd, J = 7.9, 1.9, 0.9 Hz, 1H), 7.41 (t, J = 7.9 Hz, 1H), 4.38 – 4.25 (m, 2H),
4.20 – 4.10 (m, 2H), 3.60 (dd, J = 12.7, 3.2 Hz, 1H), 2.35 – 2.17 (m, 2H), 2.18 – 2.02
(m, 2H), 1.49 – 1.36 (m, 2H), 1.31 (t, J = 7.1 Hz, 3H), 1.22 (t, J = 7.1 Hz, 3H), 1.06 (s,
3H), 0.83 (s, 3H). 13C {1H} NMR (101 MHz, CDCl3) δ 202.1, 171.8, 171.4, 140.4,
135.1, 132.9, 130.1, 128.3, 126.5, 61.7, 61.6, 54.7, 48.9, 38.6, 33.3, 31.2, 30.1, 26.7,
20.2, 14.3, 14.1. HR-MALDI-MS m/z calcd. for C21H27ClNaO5 [M+Na]+: 417.1439,
found: 417.1436.
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Diethyl 3-(3,4-dimethylbenzoyl)-4,4-dimethylcyclohexane-1,1-dicarboxylate (2i):
Colorless oil. 33.0 mg, 85% yield. IR (KBr): 2925, 2862, 1680, 1349, 1160, 722, 545
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cm-1. H NMR (400 MHz, CDCl3) δ 7.69 – 7.61 (m, 2H), 7.14 (d, J = 7.7 Hz, 1H),
4.28 – 4.16 (m, 2H), 4.12 – 4.03 (m, 2H), 3.55 (dd, J = 12.6, 3.3 Hz, 1H), 2.25 (s, 3H),
2.24 (s, 3H), 2.21 – 2.10 (m, 2H), 2.09 – 1.96 (m, 2H), 1.37 – 1.29 (m, 2H), 1.23 (t, J
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= 7.1 Hz, 3H), 1.15 (t, J = 7.1 Hz, 3H), 0.98 (s, 3H), 0.75 (s, 3H). C {1H} NMR
(101 MHz, CDCl3) δ 203.1, 172.0, 171.5, 142.5, 137.1, 136.8, 129.9, 129.4, 126.2,
61.6, 61. 5, 54.8, 48.3, 38.7, 33.2, 31.3, 30.2, 26.8, 20.4, 20.1, 20.0, 14.3, 14.2.
HR-MALDI-MS m/z calcd. for C23H32NaO5 [M+Na]+: 411.2142, found: 411.2137.
Diethyl 3-(1-naphthoyl)-4,4-dimethylcyclohexane-1,1-dicarboxylate (2j):
Colorless oil. 27.9 mg, 68% yield. IR (KBr): 2984, 1727, 1684, 1459, 1246, 1156,
793 cm-1. 1H NMR (400 MHz, CDCl3) δ 8.39 (d, J = 8.5 Hz, 1H), 7.96 (d, J = 8.3 Hz,
1H), 7.93 – 7.84 (m, 2H), 7.62 – 7.48 (m, 3H), 4.37 – 4.24 (m, 2H), 4.24 – 4.14 (m,
2H), 3.70 (dd, J = 12.8, 3.3 Hz, 1H), 2.50 – 2.34 (m, 1H), 2.31 – 2.18 (m, 2H), 2.11
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(td, J = 13.6, 4.7 Hz, 1H), 1.44 – 1.33 (m, 2H), 1.31 (t, J = 7.1 Hz, 3H), 1.25 (t, 3H),
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1.14 (s, 3H), 0.74 (s, 3H). C {1H} NMR (101 MHz, CDCl3) δ 207.3, 172.0, 171.5,
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139.0, 134.2, 132.3, 129.8, 128.6, 127.9, 127.2, 126.5, 125.8, 124.6, 61.7, 61.5, 54.9,
53.2, 38.9, 33.9, 31.4, 30.1, 26.8, 20.2, 14.3, 14.2. HR-MALDI-MS m/z calcd. for
C25H30NaO5 [M+Na]+: 433.1985, found: 433.1978.
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(5,5-Bis(methoxymethyl)-2,2-dimethylcyclohexyl)(phenyl)methanone (2k):
Colorless oil. 28.3 mg, 93% yield. IR (KBr): 2921, 2866, 1680, 1451, 1112, 689 cm-1.
1H NMR (400 MHz, CDCl3) δ 7.84 (dd, J = 5.2, 3.4 Hz, 2H), 7.52 – 7.43 (m, 1H),
7.41 – 7.33 (m, 2H), 3.43 – 3.35 (m, 3H), 3.33 (s, 3H), 3.24 (s, 3H), 3.13 – 3.06 (m,
2H), 1.62 (q, J = 14.3 Hz, 2H), 1.55 – 1.35 (m, 2H), 1.26 – 1.15 (m, 1H), 1.24 – 1.12
(m, 2H), 0.99 (s, 3H), 0.80 (s, 3H). 13C {1H} NMR (101 MHz, CDCl3) δ 204.0, 139.0,
132.7, 128.6, 128.2, 79.8, 72.9, 59.5, 59.5, 47.7, 38.8, 37.8, 33. 9, 31.4, 29.3, 25.8,
20.2. HR-MALDI-MS m/z calcd. for C19H28NaO3 [M+Na]+: 327.1931, found:
327.1933.
(3-Benzoyl-4,4-dimethylcyclohexane-1,1-diyl)bis(methylene) diacetate (2l):
Colorless oil. 31.3 mg, 87% yield. IR (KBr): 2925, 2854, 1735, 1680, 1231, 1037,
691 cm-1. 1H NMR (400 MHz, CDCl3) δ 7.85 (dd, J = 10.9, 3.7 Hz, 2H), 7.53 – 7.47
(m, 1H), 7.45 – 7.35 (m, 2H), 4.27 (d, J = 11.4 Hz, 1H), 4.05 (d, J = 11.4 Hz, 1H),
3.95 – 3.76 (m, 2H), 3.46 (dd, J = 13.1, 3.2 Hz, 1H), 1.99 (s, 3H), 1.98 (s, 3H), 1.85 –
1.75 (m, 1H), 1.45 (dtd, J = 16.3, 13.6, 6.7 Hz, 4H), 1.24 (dd, J = 10.4, 7.7 Hz, 1H),
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0.94 (s, 3H), 0.79 (s, 3H). C {1H} NMR (101 MHz, CDCl3) δ 203.5, 171.3, 171.2,
138. 9, 133.0, 128.8, 128.3, 70.1, 63.4, 47.0, 37.2, 37.1, 33.9, 31.6, 28.5, 25.3, 21.0,
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20.1. HR-MALDI-MS m/z calcd. for C21H28NaO5 [M+Na]+: 383.1829, found:
383.1826.
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Colorless oil. 29.6 mg, 89% yield. IR (KBr): 3458, 2960, 2930, 2865, 1727, 1243
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cm-1. H NMR (400 MHz, CDCl3) δ 7.99 (dt, J = 8.6, 1.7 Hz, 2H), 7.61 – 7.52 (m,
1H), 7.51 – 7.41 (m, 2H), 3.83 (s, 3H), 3.71 (s, 3H), 3.65 (dd, J = 12.6, 3.3 Hz, 1H),
2.33 – 2.20 (m, 2H), 2.20 – 2.06 (m, 2H), 1.47 – 1.32 (m, 2H), 1.07 (s, 3H), 0.83 (s,
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3H). C {1H} NMR (101 MHz, CDCl3) δ 203.2, 172.3, 171.9, 138.9, 133.0, 128.7,
128.3, 54.9, 52.9, 52.8, 48.6, 38.7, 33.2, 31.3, 30.3, 26.9, 20.3. HR-MALDI-MS m/z
calcd. for C19H24NaO5 [M+Na]+: 355.1516, found: 355.1517.
2,2-Dimethyl-5,5-bis(phenylsulfonyl)cyclohexyl)(phenyl)methanone (2n):
White solid. 41.7 mg, 84% yield. mp: 147.4–147.8 °C. IR (KBr): 2933, 2854, 1448,
1341, 1156, 923, 746 cm-1. 1H NMR (400 MHz, CDCl3) δ 8.12 (d, J = 7.4 Hz, 2H),
8.07 – 8.02 (m, 2H), 8.01 – 7.96 (m, 2H), 7.71 (dt, J = 10.1, 7.1 Hz, 2H), 7.63 – 7.56
(m, 5H), 7.47 (t, J = 7.6 Hz, 1H), 4.45 (dd, J = 12.7, 3.6 Hz, 1H), 2.89 (dd, J = 15.5,
12.8 Hz, 1H), 2.65 – 2.53 (m, 1H), 2.34 – 2.17 (m, 3H), 1.50 – 1.39 (m, 1H), 0.87 (s,
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3H), 0.83 (s, 3H). C {1H} NMR (101 MHz, CDCl3) δ 202.6, 138.5, 136.3, 135.9,
134.8, 134.7, 133. 5, 131.7, 131.3, 128.9, 128.8, 128.8, 128.4, 87.5, 46.5, 36.8, 32.8,
31.0, 26.4, 22.1, 19.6. HR-MALDI-MS m/z calcd. for C27H28NaO5S2 [M+Na]+:
519.1270, found: 519.1270.
(4,4-Dimethyl-1-tosylpiperidin-3-yl)(phenyl)methanone (2o):
White solid. 24.3 mg, 65% yield. mp: 120.4–120.9 °C. IR (KBr): 2925, 1787, 1353,
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1160, 742, 553 cm-1. 1H NMR (400 MHz, CDCl3) δ 7.94 – 7.89 (m, 2H), 7.68 – 7.63
(m, 2H), 7.62 – 7.55 (m, 1H), 7.51 – 7.43 (m, 2H), 7.34 (d, J = 8.0 Hz, 2H), 3.75 –
3.59 (m, 3H), 2.82 – 2.72 (m, 1H), 2.55 – 2.47 (m, 1H), 2.46 (s, 3H), 1.77 (td, J =
13.2, 4.6 Hz, 1H), 1.46 (dt, J = 13.5, 2.7 Hz, 1H), 0.86 (s, 3H), 0.83 (s, 3H). 13C {1H}
NMR (101 MHz, CDCl3) δ 201.5, 143.8, 138.3, 133.5, 133.3, 129.9, 128.8, 128.4,
127. 8, 50.9, 44.6, 42. 6, 40.1, 32. 6, 31.3, 21.7, 19.9. HR-MALDI-MS m/z calcd. for
C21H25NNaO3S [M+Na]+: 394.1447, found: 394.1443.
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(4,4-Dimethyl-1-tosylpiperidin-3-yl)(thiophen-3-yl)methanone (2p):
Colorless oil. 23.4 mg, 62% yield. IR (KBr): 2925, 2580, 1664, 1357, 1164, 1093,
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955 cm-1. H NMR (400 MHz, CDCl3) δ 8.00 (dd, J = 2.8, 1.2 Hz, 1H), 7.58 (d, J =
8.3 Hz, 2H), 7.46 (dd, J = 5.1, 1.2 Hz, 1H), 7.32 – 7.23 (m, 3H), 3.68 – 3.53 (m, 2H),
3.33 (dd, J = 11.5, 3.7 Hz, 1H), 2.67 (t, J = 11.8 Hz, 1H), 2.49 – 2.32 (m, 4H), 1.75 –
1.63 (m, 1H), 1.38 (ddd, J = 9.0, 5.9, 2.2 Hz, 1H), 0.87 (s, 3H), 0.77 (s, 3H). 13C {1H}
NMR (101 MHz, CDCl3) δ 195.1, 143.8, 143.5, 133.3, 133.2, 130.0, 127. 8, 127.3,
126.8, 53.3, 44.5, 42.5, 40.1, 32.5, 31.4, 21.7, 19.8. HR-MALDI-MS m/z calcd. for
C19H23NNaO3S2 [M+Na]+: 400.1012, found: 400.1007.
(4,4-Dimethyl-1-tosylpiperidin-3-yl)(4-methoxyphenyl)methanone (2q):
White solid. 28.1 mg, 70% yield. mp: 137.4–137.9 °C. IR (KBr): 2956, 2925, 2854,
1455, 1337, 1164, 545 cm-1. 1H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 8.3 Hz, 2H),
7.25 (d, J = 7.2 Hz, 2H), 6.98 – 6.95 (m, 1H), 6.81 (d, J = 2.3 Hz, 1H), 6.68 (dd, J =
8.2, 2.4 Hz, 1H), 3.80 – 3.76 (m, 2H), 3.74 (s, 3H), 3.73 – 3.69 (m, 1H), 3.30 (t, J =
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5.7 Hz, 2H), 2.50 – 2.44 (m, 2H), 2.35 (s, 3H), 1.13 (s, 6H). C {1H} NMR (101
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MHz, CDCl3) δ 158.3, 155.3, 143. 7, 142.3, 134.7, 134.1, 130.7, 129.9, 127.7, 118.8,
111.2, 108.5, 55.7, 48.7, 43.3, 43.0, 24. 5, 22.6, 21. 7. HR-MALDI-MS m/z calcd. for
C22H27NNaO4S [M+Na]+: 424.1553, found: 424.1547.
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(4,4-Dimethyl-1-tosylpiperidin-3-yl)(4-(trifluoromethyl)phenyl)methanone (2r):
White solid. 27.6 mg, 63% yield. mp: 140.4–140.9 °C. IR (KBr): 2958, 2931, 1447,
1344, 1161, 1093, 907, 759, 553 cm-1. 1H NMR (400 MHz, CDCl3) δ 7.95 (d, J = 8.2
Hz, 2H), 7.68 (d, J = 8.2 Hz, 2H), 7.59 (d, 2H), 7.28 (d, J = 8.0 Hz, 2H), 3.67 – 3.52
(m, 3H), 2.72 (t, J = 12.4 Hz, 1H), 2.49 – 2.40 (m, 1H), 2.39 (s, 3H), 1.77 – 1.64 (m,
1H), 1.41 (dt, J = 13.7, 2.8 Hz, 1H), 0.79 (s, 3H), 0.75 (s, 3H). 13C {1H} NMR (101
MHz, CDCl3) δ 200.8, 143.9, 141.0, 133.3, 130.0, 128.7, 128.5 (q, J = 413.0 Hz),
127.8, 126.0 (q, J = 3.7 Hz), 51.5, 44.4, 42.5, 40.0, 32.8, 31.4, 21.7, 19.9. 19F NMR
(377 MHz, CDCl3) δ -63.13. HR-MALDI-MS m/z calcd. for C22H24F3NNaO3S
[M+Na]+: 462.1321, found: 462.1321.
(4,4-Dimethyl-1-tosylpyrrolidin-3-yl)(phenyl)methanone (4a):
Colorless oil. 25.4 mg, 71% yield. IR (KBr): 2968, 2882, 1676, 1345, 1160, 1101,
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663 cm-1. H NMR (400 MHz, CDCl3) δ 7.78 – 7.68 (m, 4H), 7.54 – 7.47 (m, 1H),
7.43 – 7.36 (m, 2H), 7.29 (d, J = 7.9 Hz, 2H), 3.73 (t, J = 7.6 Hz, 1H), 3.60 (ddd, J =
28.4, 10.0, 7.6 Hz, 2H), 3.16 (d, J = 9.5 Hz, 1H), 3.04 (d, J = 9.5 Hz, 1H), 2.39 (s,
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3H), 1.04 (s, 3H), 0.62 (s, 3H). C {1H} NMR (101 MHz, CDCl3) δ 199.1, 143.6,
137.8, 134.0, 133.6, 129.8, 128.9, 128.5, 127.8, 61.0, 53.2, 49.7, 42.5, 27.6, 22.4, 21.7.
HR-MALDI-MS m/z calcd. for C20H23NNaO3S [M+Na]+: 380.1291, found: 380.1289.
(4,4-Dimethyl-1-tosylpyrrolidin-3-yl)(4-fluorophenyl)methanone (4b):
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White solid. 24.8 mg, 66% yield. mp: 79.8–80.5 °C. IR (KBr): 2930, 2854, 1545,
1156, 1015, 927 cm-1. 1H NMR (400 MHz, CDCl3) δ 7.82 – 7.75 (m, 2H), 7.73 – 7.67
(m, 2H), 7.29 (d, J = 7.9 Hz, 2H), 7.10 – 7.00 (m, 2H), 3.67 (dd, J = 14.2, 6.6 Hz, 1H),
3.62 – 3.51 (m, 2H), 3.16 (d, J = 9.5 Hz, 1H), 3.04 (d, J = 9.5 Hz, 1H), 2.39 (s, 3H),
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1.06 (s, 3H), 0.62 (s, 3H). C {1H} NMR (101 MHz, CDCl3) δ 197.5, 166.1 (d, J =
260.0 Hz), 143.7, 134.2 (d, J = 3.1 Hz), 134.0, 131.2 (d, J = 9.4 Hz), 129.8, 127.8,
116.0 (d, J = 21.9 Hz) 61.0, 53.2, 49.8, 42.6, 27.7, 22.5, 21.8. 19F NMR (377 MHz,
CDCl3) δ -104.28. HR-MALDI-MS m/z calcd. for C20H22FNNaO3S [M+Na]+:
398.1197, found: 398.1192.
(4-Chlorophenyl)(4,4-dimethyl-1-tosylpyrrolidin-3-yl)methanone (4c):
White solid. 25.0 mg, 64% yield. mp: 78.4–79.0 °C. IR (KBr): 2965, 2925, 2865,
1345, 1015, 670 cm-1. 1H NMR (400 MHz, CDCl3) δ 7.69 (d, J = 8.4 Hz, 3H), 7.61 (d,
J = 7.8 Hz, 1H), 7.47 (d, J = 7.9 Hz, 1H), 7.36 – 7.26 (m, 3H), 3.71 – 3.48 (m, 3H),
3.15 (d, J = 9.5 Hz, 1H), 3.04 (d, J = 9.5 Hz, 1H), 2.40 (s, 3H), 1.04 (s, 3H), 0.63 (s,
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3H). C {1H} NMR (101 MHz, CDCl3) δ 198.0, 143.7, 139.3, 135.3, 133.9, 133.5,
130.2, 129.9, 128.5, 127.8, 126.6, 60.9, 53.4, 49.6, 42.7, 27.6, 22. 5, 21.8.
HR-MALDI-MS m/z calcd. for C20H22ClNNaO3S [M+Na]+: 414.0901, found:
414.0896.
(4-Methyl-4-phenyl-1-tosylpyrrolidin-3-yl)(phenyl)methanone (4d):
Colorless oil. 25.6 mg, 61% yield. IR (KBr): 2916, 1599, 1451, 1333, 1156, 1108,
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908, 754, 563 cm-1. H NMR (400 MHz, CDCl3) δ 7.79 – 7.73 (m, 2H), 7.58 – 7.46
(m, 3H), 7.38 – 7.30 (m, 4H), 7.11 – 7.03 (m, 3H), 6.95 – 6.88 (m, 2H), 4.18 (dd, J =
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Hz, 1H), 3.55 (dt, J = 16.2, 8.1 Hz, 1H), 2.44 (s, 3H), 1.47 (s, 3H). C {1H} NMR
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(101 MHz, CDCl3) δ 199.4, 143.6, 143.1, 137.3, 134.3, 133.2, 129.9, 128. 7, 128.4,
128.1, 127.6, 126.6, 125.9, 57.9, 53.4, 50.2, 50.1, 30.1, 21.7. HR-MALDI-MS m/z
calcd. for C25H25NNaO3S [M+Na]+: 442.1447, found: 442.1447.
3-(Prop-1-en-2-yl)-4-(thiophen-2-yl)-1-tosyl-1,2,3,6-tetrahydropyridine (6):
White solid. 24.4 mg, 68% yield. mp: 142.4–143.1 °C. IR (KBr): 3075, 2854, 1471,
1333, 1156, 663 cm-1. 1H NMR (400 MHz, CDCl3) δ 7.61 (d, J = 8.3 Hz, 2H), 7.25 (d,
J = 8.0 Hz, 2H), 7.04 (dd, J = 3.8, 2.4 Hz, 1H), 6.88 – 6.80 (m, 2H), 6.06 – 5.99 (m,
1H), 4.87 (s, 1H), 4.79 (s, 1H), 4.04 – 3.94 (m, 1H), 3.66 (dt, J = 33.0, 16.5 Hz, 1H),
3.32 (ddd, J = 13.3, 6.6, 4.2 Hz, 1H), 3.21 (s, 1H), 2.75 (dd, J = 11.6, 4.1 Hz, 1H),
2.36 (s, 3H), 1.77 (s, 3H). 13C {1H} NMR (101 MHz, CDCl3) δ 143.9, 143.8, 143. 7,
133.4, 131.9, 129. 8, 127.9, 127. 5, 123.9, 123.3, 119.6, 115.1, 47.3, 45.7, 45.0, 29.8,
21. 7, 21.6. HR-MALDI-MS m/z calcd. for C19H21NNaO2S2 [M+Na]+: 382.0906,
found: 382.0904.
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Ethyl
5,5-dimethyl-2-oxo-3-(3-phenylprop-2-yn-1-yl)tetrahydrofuran-3-carboxylate
(8):
Colorless oil. 24.0 mg, 80% yield. IR (KBr): 2935, 2854, 1355, 1165, 758, 655, 541
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cm-1. H NMR (400 MHz, CDCl3) δ 7.39 (dd, J = 7.1, 2.6 Hz, 2H), 7.33 – 7.20 (m,
2H), 4.37 – 4.17 (m, 2H), 3.24 – 3.10 (m, 1H), 3.05 (d, J = 16.9 Hz, 1H), 2.66 (t, J =
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14.6 Hz, 1H), 2.57 (t, J = 18.4 Hz, 1H), 1.61 (s, 6H), 1.33 (t, 3H). C {1H} NMR
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(101 MHz, CDCl3) δ 173.2, 169. 8, 131.8, 128.4, 122.9, 84.4, 84.0, 83.0, 62.8, 56.9,
43.2, 29.9, 28.9, 26.5, 14.1. HR-MALDI-MS m/z calcd. for C18H20NaO4 [M+Na]+:
323.1254, found: 323.1256.
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Phenyl(4a,8,8-trimethyl-2-tosyldecahydroisoquinolin-4-yl)methanone (10a):
White solid. 29.0 mg, 66% yield. mp: 124.4–125.0 °C. IR (KBr): 3445, 2925, 2854,
1633, 1160, 714, 549 cm-1. 1H NMR (400 MHz, CDCl3) δ 7.85 – 7.80 (m, 2H), 7.67
(d, J = 8.3 Hz, 2H), 7.57 – 7.51 (m, 1H), 7.44 (dd, J = 10.5, 4.7 Hz, 2H), 7.29 (t, J =
6.7 Hz, 2H), 3.72 – 3.65 (m, 2H), 3.22 (dd, J = 4.7, 2.0 Hz, 1H), 3.11 (dd, J = 12.9,
4.8 Hz, 1H), 2.62 – 2.53 (m, 2H), 2.43 (s, 3H), 1.59 – 1.53 (m, 1H), 1.47 (dd, J = 12.6,
3.1 Hz, 1H), 1.37 (ddd, J = 13.4, 10.6, 5.7 Hz, 2H), 1.31 – 1.22 (m, 2H), 1.11 (s, 3H),
0.95 (s, 3H), 0.81 (s, 3H). 13C {1H} NMR (101 MHz, CDCl3) δ 200.5, 143.4, 138.4,
134.5, 133.0, 129.7, 128.8, 128.2, 127.8, 51.6, 44.2, 43.2, 42.3, 41.7, 36.5, 36.3, 33.0,
32.5, 22.3, 21.7, 21.0, 18.6. HR-MALDI-MS m/z calcd. for C26H33NNaO3S [M+Na]+:
462.2073, found: 462.2073.
p-Tolyl(4a,8,8-trimethyl-2-tosyldecahydroisoquinolin-4-yl)methanone (10b):
White solid. 30.8 mg, 68% yield. mp: 154.4–154.9 °C. IR (KBr): 2921, 2854, 1522,
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1160, 742 cm-1. H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 8.2 Hz, 2H), 7.67 (d, J =
8.3 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 3.71 – 3.60 (m, 2H),
3.20 (dd, J = 4.7, 2.1 Hz, 1H), 3.11 (dd, J = 12.9, 4.7 Hz, 1H), 2.69 – 2.53 (m, 2H),
2.42 (s, 3H), 2.40 (s, 3H), 1.62 – 1.50 (m, 1H), 1.45 (dd, J = 12.6, 3.2 Hz, 1H), 1.41 –
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1.32 (m, 2H), 1.30 – 1.20 (m, 2H), 1.11 (s, 3H), 0.94 (s, 3H), 0.80 (s, 3H). C {1H}
NMR (101 MHz, CDCl3) δ 200.1, 143.8, 143.3, 135.6, 134.6, 129.6, 129. 5, 128.3,
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HR-MALDI-MS m/z calcd. for C27H35NNaO3S [M+Na]+: 476.2230, found: 476.2228.
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(10c):
White solid. mp: 188.7–189.1 °C. 31.8 mg, 64% yield. IR (KBr): 2925, 2854, 1727,
1282, 1156, 1105, 730 cm-1. 1H NMR (400 MHz, CDCl3) δ 8.15 – 8.06 (m, 2H), 7.90
– 7.81 (m, 21H), 7.69 – 7.63 (m, 2H), 7.29 (d, J = 8.0 Hz, 2H), 3.95 (s, 3H), 3.72 –
3.63 (m, 2H), 3.19 (dd, J = 4.6, 2.0 Hz, 1H), 3.09 (dd, J = 12.8, 4.7 Hz, 1H), 2.60 –
2.52 (m, 2H), 2.43 (s, 3H), 1.64 – 1.59 (m, 2H), 1.49 – 1.39 (m, 2H), 1.27 (ddd, J =
15.5, 11.7, 3.5 Hz, 2H), 1.11 (s, 3H), 0.96 (s, 3H), 0.80 (s, 3H). 13C {1H} NMR (101
MHz, CDCl3) δ 200.1, 166.3, 143.5, 141.7, 134.5, 133.7, 130.0, 129.7, 128.0, 127.8,
52.6, 52.2, 44.3, 43.1, 42.4, 41.7, 36.5, 36.4, 33.0, 32.5, 22.3, 21.7, 21.0, 18.6.
HR-MALDI-MS m/z calcd. for C28H35NNaO5S [M+Na]+: 520.2128, found: 520.2128.
(4-Fluorophenyl)(4a,8,8-trimethyl-2-tosyldecahydroisoquinolin-4-yl)methanone
(10d):
White solid. mp: 166.5–167.0 °C. 28.8 mg, 63% yield. IR (KBr): 2929, 2854, 1546,
1156, 1014, 927 cm-1. H NMR (400 MHz, CDCl3) δ 7.86 (ddd, J = 8.3, 5.2, 2.5 Hz,
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2H), 7.67 (d, J = 8.2 Hz, 2H), 7.30 (d, J = 7.9 Hz, 2H), 7.16 – 7.06 (m, 2H), 3.70 –
3.60 (m, 2H), 3.16 (dd, J = 4.6, 1.9 Hz, 1H), 3.12 – 3.05 (m, 1H), 2.62 – 2.50 (m, 2H),
2.43 (s, 3H), 1.64 – 1.56 (m, 2H), 1.46 – 1.36 (m, 2H), 1.30 – 1.21 (m, 2H), 1.11 (s,
3H), 0.95 (s, 3H), 0.81 (s, 3H). 13C {1H} NMR (101 MHz, CDCl3) δ 198.8, 165.6 (d,
J = 254.8 Hz), 143.4, 134.7 (d, J = 17.4 Hz), 130.8 (d, J = 9.2 Hz), 129.7, 127.8,
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