Phosphine-Catalyzed Intermolecular Dienylation of Alkynoate with para-Quinone Methides

Article abstract of DOI:10.1021/acs.joc.1c00226

An interesting remote I-C 1,6-Addition and an isomerization cascade reaction for phosphine-catalyzed activated alkynes have been disclosed. The products featuring a functional diene and a 1,1-diaryl methyl motif have been obtained in moderate to good yields (30-86%) by applying para-quinone methides (p-QMs) and I-substituted alkynoate with tributylphosphine (PnBu3) catalysis, along with high regioselectivity and stereoselectivity (dr > 20:1). The wide scope of compatible substrates (35 examples), such as indolyl, oxindolyl, ester, and cinnamyl, expand the utility of this methodology. A plausible mechanism and some applications of it have also been presented.

Full text of DOI:10.1021/acs.joc.1c00226

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Article
Phosphine-Catalyzed Intermolecular Dienylation of Alkynoate with
para-Quinone Methides
Zefeng Song,# Weijia Wang,# Zhixin Liu, Yue Lu, and De Wang*
Cite This: J. Org. Chem. 2021, 86, 8590−8599
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ABSTRACT: An interesting remote δ-C 1,6-addition and an isomerization cascade reaction for phosphine-catalyzed activated
alkynes have been disclosed. The products featuring a functional diene and a 1,1-diaryl methyl motif have been obtained in moderate
to good yields (30−86%) by applying para-quinone methides (p-QMs) and δ-substituted alkynoate with tributylphosphine (PnBu3)
catalysis, along with high regioselectivity and stereoselectivity (dr > 20:1). The wide scope of compatible substrates (35 examples),
such as indolyl, oxindolyl, ester, and cinnamyl, expand the utility of this methodology. A plausible mechanism and some applications
of it have also been presented.
usually require harsh conditions. Therefore, the development
of new C4 synthetic platforms and practical methods in
dienyation reaction remains highly attractive.
INTRODUCTION
■
Conjugated dienes widely exist in natural products and
pharmaceutical molecules.1 They also serve as important
building blocks in the modern organic synthesis.2 A number of
methods focusing on the synthesis of conjugated 1,3-dienes
have been developed. The most common strategy is using
transition metals to catalyze the cross coupling of two C2 units,
generating the corresponding 1,3-dienes (Scheme 1, eq 1).1,2
Trost’s group first disclosed that electron-deficient alky-
noates or alkynones could serve as precursors of dienes in the
phosphine-catalyzed alkyne intramolecular isomerization
(Scheme 2, eq 1).4 But there have been very few works
related with the intermolecular dienylation of alkynoates under
phosphine catalysis, as the 1,3-dipolar cycloaddition dominates
when an electrophile exists (Scheme 2, eq 2).5,6 Shi and Wei’s
groups have reported an interesting alkynone δ-addition to
highly activated ketones or ketimines by phosphine catalysis
yet with the strong limitation of alkynyl substituents.7 Until
now, there are no records about a high tolerance on
substituents when applying alkynoate intermolecular dienyla-
tion to alkene compounds. Based on our continuous efforts
exploring Lewis base catalysis,8 hereby for the first time we
report the phosphine-catalyzed direct dienylation of alkynoate
with para-quinone methides (Scheme 2, eq 3).
Scheme 1. Synthesis of Conjugated Dienes
Despite its effectiveness, this approach also has disadvantages
of poor stereoselectivity control and limited substituents.
Alternatively, a C4 unit serving directly as diene precursor will
bring a more efficient and convergent synthesis of 1,3-dienes. A
series of diene precursors, e.g. alkoxy-1,3-dienes, dienylboro-
nates, dienylsilane, and sulfolenes have been synthesized and
successfully applied in the dienylation reactions (Scheme 1, eq
2).3 However, these highly activated diene precursors are
difficult to prepare and store, and the reactions with them
Received: January 29, 2021
Published: June 24, 2021
https://doi.org/10.1021/acs.joc.1c00226
© 2021 American Chemical Society
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substituted group (R1 = 3,4,5-(MeO)3C6H2), the reactions also
proceeded efficiently to afford the products 3g−3i in 57−78%
yields, slightly lower due to the affection of electronic donating.
Functional groups such as 4-CF3 or 4-NO2 showed good
tolerance in this reaction with high yields (3j−3k 83−86%).
When R1 was either a heteroaromatic ring (R1 = 2-thiophene,
3-pyridinyl) or a sterically bulkier 2-naphthalene moiety, the
reactions proceeded smoothly to generate products 3l−3n in
moderate yields ranging from 52% to 65%. When iPr (R2) was
applied, however, the corresponding product 3o was obtained
in significantly reduced yield (37%). Other activated alkynyl
compounds such as phenyl esters, amide, or different
substituent groups on R3 were also suitable substrates to this
reaction, giving the products in 33−85% yields with high
stereoselectivities (>20:1 dr). Moreover, aliphatic groups such
as ethyl hex-2-ynoate or ethyl hept-2-ynoate were also
smoothly transformed into the desired products 3u−3v with
53−58% yields.
Then, we turned our attentions to further expanding the
substrate scope of the reaction with other 1,6-conjugated p-
QMs. The results were summarized in Table 3. The tolerance
of the indolyl group in this methodology was clearly showed
through the 82% yield of product 4a. 5-Chloroindonyl and 4-/
6-bromoindolnyl were smoothly converted to the correspond-
ing diene products 4b−4d in 67−85% yields with high
stereoselectivities as well as regioselectivities. When an N-
methyl protected indolyl substrate was applied, the product 4e
was generated in 56% yield, strongly indicating the affections of
the electron-donating group. Similarly, the tolerance of various
oxindolyl substrates were also proven in the established
reaction system, although yields of products 5a−5f were
moderate (42−53% isolated yield, 58−76% brsm yield). These
results indicate that complex molecules could be achieved
through the phosphine catalysis strategy. The configurations of
the diene compounds were determined by X-ray diffraction of
4a and 4c.
A plausible mechanism is proposed in Scheme 3 based on
our experiments and previous reports.4,5,10 Initially, nucleo-
philic phosphine attacks alkynoate 2 to form a counterion Int-
A with the assistant of proton shuttle (HA), which is then
transformed to Int-B via a 1,3-proton shift. A highly activated
zwitterionic intermediate Int-C was generated upon the
elimination of HA, which then performed a 1,4-proton shift
resulting in the formation of Int-D.11 Afterward, Int-D
underwent a δ-addition with p-QM to give a phenolate Int-E
and subsequently an α-proton shift process to form Int-F.8 Int-
F is then transformed to Int-G via another proton shift which
coexists with its resonance phosphorus ylide Int-H. Finally, the
sequence of 1,2-proton shift and elimination led to the
dienylation product and regenerated the catalyst.
To better understand the reaction mechanism, a deuterium
labeling experiment was carried out (Scheme 4, eq 1). As
expected, the reaction of 1l and 2a in the presence of D2O (10
equiv) generated the corresponding product 3l-D with
incorporation of 77%, 42%, and 42% deuterium ratio at αC,
βC, and γC, respectively. We also synthesized the alkynoate’s
equivalence compound, allenoate 6, and applied it in the
reaction; the desired product 3a was successfully obtained in
27% yield without additives at room temperature (Scheme 4,
eq 2). These observations further confirmed the proton
transfer process in the proposed mechanism.
Scheme 2. Phosphine-Catalyzed Activated Alkynes
RESULTS AND DISCUSSION
■
In the initial experiments we applied para-quinone methide (p-
QM)9 1a and ethyl 5-phenylpent-2-ynoate 2a as model
substrates to identify the optimal reaction conditions (Table
1). Using 20 mol % PPh3 or nucleophilic stronger PnBu3 as
catalysts, no desired product was detected when the reaction
system heated to 60 °C or even 120 °C (Table 1, entries 1−3).
Adding benzoic acid as additive to the PnBu3-catalyzed
reaction, a highly regioselective and stereoselective dienylated
product 3a was obtained in 26% yield (Table 1, entry 4).
Different types of phosphines have also been examined for the
cascade remote 1,6-addition and dienylation (Table 1, entries
5−9). No enhanced reactivity was observed using phosphines
PMePh2, PMe2Ph, or PMe3 (6−12% yields), and no reaction
took place in the presence of PCy3 or PtBu3 probably due to
the bulky substitution group in the catalysts. Increasing the
temperature of the PnBu3-catalyzed reaction to 70−80 °C, the
desired product had a slightly enhanced yield, but then became
decomposed when the temperature was further increased to
100 °C (Table 1, entries 10−12). Different protic additives
(cocatalyst) were also investigated since acidity protons may
have influence on the isomerization of alkynoates (Table 1,
entries 13−23).4 With phenol, acetic acid, and HFIP as
additives, low reactivities were observed. After screening
aromatic acids, it was found that 20 mol % 2-nitrobenzoic
acid (2-NO2BzOH) as a cocatalyst gave the best result (57%
yield, entry 19). Analysis of different solvents showed that the
reaction with toluene generated the highest yield (Table 1,
entries 24−28). Increasing the loading of PnBu3 to 30 mol %,
the desired product was obtained in 80% yield (entry 29).
Further increasing the catalyst loading to 50 mol %, the
corresponding product was generated in almost the same yield
(entry 30). Increasing the additive loading, the yield of product
slightly dropped to 75% (entry 31). Tertiary amines, such as
DMAP or DABCO, could not trigger this 1,6-addition and
dienylation in the current reaction system (entries 32−33).
Under the optimum conditions, we then screened the
generality of this addition/dienylation with various p-QMs 1
and alkynoates 2. The results are summarized in Table 2. It
was found that p-QMs 1b−1f bearing different electron-
deficient halogen substitution on aromatic rings (4-Br, 3-Br, 2-
Br, 4-Cl, 4-F) gave the corresponding products 3b−3f in good
yield (64−84%) with high stereoselectivities and high
regioselectivities (>20:1 dr). When R1 was an electron-rich
aromatic ring (R1 = 4-MeC6H4, 4-MeOC6H4) or a multi-
Enlarging the reaction scale (1.0 mmol) afforded 4a in 76%
yield and >20:1 dr under the standard conditions (Scheme 5,
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Table 1. Screening of Reaction Conditions
a
b
entry
cat.
PPh3
PPh3
PnBu3
PnBu3
PMePh2
PMe2Ph
PMe3
PCy3
load (x mol %)
solvent
toluene
T (°C)
additive
yield (%)
1
2
3
4
5
6
7
8
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
30
50
30
20
20
20
60/120
60/120
nr
nr
nr
26
6
15
12
d
nr
30
30
7
nr
nr
nr
14
d
12
57
15
27
nr
55
34
d
c
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
THF
c
60
60
60
60
60
60
70
80
100
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
BzOH
BzOH
BzOH
BzOH
BzOH
BzOH
BzOH
BzOH
BzOH
PhOH
CH3CO2H
HFIP
4-BrBzOH
2-MeBzOH
3,5-(MeO)2BzOH
2-NO2BzOH
4-NO2BzOH
3,5-(NO2)2BzOH
TsOH
2-HOBzOH
2-HO2BzOH
2-HO2BzOH
2-HO2BzOH
2-HO2BzOH
2-HO2BzOH
2-HO2BzOH
2-HO2BzOH
2-HO2BzOH
none/acid
none/acid
9
PtBu3
PnBu3
PnBu3
PnBu3
PnBu3
PnBu3
PnBu3
PnBu3
PnBu3
PnBu3
PnBu3
PnBu3
PnBu3
PnBu3
PnBu3
PnBu3
PnBu3
PnBu3
PnBu3
PnBu3
PnBu3
PnBu3
PnBu3
DMAP
DABCO
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
DCM
MeCN
Et2O
1,4-dioxane
toluene
toluene
toluene
toluene
toluene
d
15
46
80
80
75
nr
nr
e
31
f
32
f
33
a
All reactions were carried out with 1a (0.1 mmol), 2a (0.12 mmol), additive (20 mol %), and catalyst (x mol %) in the corresponding solvent (1.0
b
c
d
e
f
mL). Isolated yield. 60 or 120 °C heating. Trace product, starting materials recover. Using 30 mol % 2-nitrobenzoic acid as additive. Without
additives or adding 20 mol % 2-nitrobenzoic acid as an additive.
eq 1). Surprisingly, both cinnamyl and ester substituted p-QMs
are compatible in this dienylation reaction to afford
corresponding products 9−10 in 30−42% yield with high
chemoselectivity (Scheme 5, eq 2). We have also tested
alkynoate 11 in this reaction under the standard conditions.
However, no desired product was generated (Scheme 5, eq 3).
The asymmetric dienylation was also investigated under
different chiral phosphine catalysis but with a negative result
of the desired products (see the SI).
dr). The good substituent tolerance with e.g. aryl, indolyl,
oxindolyl, cinnamyl, and ester groups widely expanded the
further transformation and application scopes of the reaction.
Mechanism studies have also revealed the possible pathway of
the reaction. Further mechanism investigations, applications,
and the asymmetric version of the reaction are ongoing in our
lab.
EXPERIMENTAL SECTION
■
General Information. Solvent purification was conducted
according to the Purification of Laboratory Chemicals.13 The NMR
spectrum was recorded on JEOL 400 (400 MHz), 1H (400 MHz) and
13C{H}NMR (100 MHz) spectra were recorded in CDCl3 (7.26 ppm
CONCLUSION
■
In conclusion, an interesting and efficient phosphine-catalyzed
cascade addition and dienylation reaction of activated alkynyl
compounds has been demonstrated. The corresponding diene
products were obtained in moderate to good yield (30−86%)
with high regioselectivities and high stereoselectivities (>20:1
1
for H NMR, 77.00 ppm for 13C{H}NMR as internal references).
Infrared (IR) spectra were recorded on a BFRL WQF-530 FT-IR
spectrometer. High-resolution mass spectra (HRMS) were recorded
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Table 2. Substrate Scopes Screening
Table 3. Scope of the Addition/Dienylation to Afford
Products 4 and 5
Compounds 4−5 and 9−10 followed the general procedure as
above.
Ethyl (2E,4Z)-6-(3,5-Di-tert-butyl-4-hydroxyphenyl)-5,6-
diphenylhexa-2,4-dienoate (3a). Compound 3a (40 mg, 80%
yield) was obtained as a yellow solid following the general procedure
from 1a (0.1 mmol) and 2a (0.12 mmol). Rf = 0.5 (PE/EtOAc =
20:1); 1H NMR (400 MHz, CDCl3) δ 7.34−7.24 (m, 6H), 7.23−7.18
(m, 3H), 7.15−7.13 (m, 2H), 6.93 (s, 2H), 5.98 (d, J = 11.6 Hz, 1H),
5.80 (d, J = 15.2 Hz, 1H), 5.19 (s, 1H), 5.10 (s, 1H), 4.13 (q, J = 7.2
Hz, 2H), 1.37 (s, 18H), 1.22 (t, J = 7.2 Hz, 3H); 13C{H} NMR (100
MHz, CDCl3) δ 167.2, 155.5, 152.3, 142.1, 142.0, 140.2, 135.5, 131.5,
129.4, 128.8, 128.3, 128.09, 128.07, 127.6, 126.4, 126.1, 121.5, 60.1,
59.7, 34.3, 30.3, 14.2; IR (neat) υ 3635, 2957, 2872, 1706, 1624,
1434, 1367, 1268, 1169, 1129, 991, 700 cm−1; mp 54−56 °C; HRMS
(ESI) m/z: [M + Na]+ Calcd for C34H40O3Na 519.2874, found:
519.2869.
on a Thermo Fisher Scientific Exactive mass spectrometer using ESI
(electrospray ionization) as the ionization method. Unless otherwise
noted, commercially obtained reagents were used without further
purification. The crystal structure of compounds 4a and 4c were
grown in ethyl ether at room temperature. 4a was collected on an
Agilent Xcalibur Eos Gemini CCD plate diffractometer, using graphite
monochromatized Cu Kα (λ = 1.54178) radiation. 4c was collected
on a Smart-1000, using graphite monochromatized Mo Kα (λ =
0.71073) radiation. The ORTEP diagrams of compound 4a and 4c
are 50% probability thermal ellipsoids. Compounds para-quinone
methides 1a−1z,9a−b 7,9c 8,9d alkynoates 2a−2h,5c and allenoates 68
and 1112 were prepared according to the previously reported
procedures; these compounds are known products. The Supporting
Information contains the structures of all compounds shown in the
main text, X-ray data of compound 4a and 4c, asymmetric trials,
NMR spectra, and deuterium-labeling experiments and spectrum of
3l-D.
General Procedure for the Synthesis of 3a−3v. To a flame-
dried Schlenk tube were added p-QMs 1 (0.1 mmol), alkyne 2 (0.12
mmol), o-NO2BzOH (0.02 mmol), and toluene sequentially under
dry nitrogen atmosphere, then PnBu3 (0.03 mmol) was added and the
mixture were stirred for 12 h at 70 °C in an oil bath. Then water (2
mL) was added to the reaction mixture and extracted with ethyl ether
(3 mL × 2). The organic layer was dried over with anhydrous Na2SO4
and filtered. The solvent was removed under reduced pressure, and
the residue was purified by column chromatography on silica gel (PE/
EtOAc = 20:1, Rf = 0.3−0.5), affording the corresponding products
3a−3v.
Ethyl (2E,4Z)-6-(4-Bromophenyl)-6-(3,5-ditert-butyl-4-hydroxy-
phenyl)-5-phenylhexa-2,4-dienoate (3b). Compound 3b (40 mg,
70% yield) was obtained as a yellow solid following the general
procedure from 1b (0.1 mmol) and 2a (0.12 mmol). Rf = 0.4 (PE/
1
EtOAc = 20:1); H NMR (400 MHz, CDCl3) δ 7.39 (d, J = 8.4 Hz,
2H), 7.31−7.24 (m, 4H), 7.12−7.10 (m, 2H), 7.04 (d, J = 8.4 Hz,
2H), 6.88 (s, 2H), 5.94 (d, J = 11.2 Hz, 1H), 5.80 (d, J = 15.6 Hz,
1H), 5.12 (s, 1H), 5.11 (s, 1H), 4.11 (q, J = 7.2 Hz, 2H), 1.36 (s,
18H), 1.21 (t, J = 7.2 Hz, 3H); 13C{H} NMR (100 MHz, CDCl3) δ
167.1, 154.7, 152.5, 141.7, 141.2, 139.8, 135.7, 131.4, 131.2, 130.9,
128.8, 128.3, 128.2, 127.8, 125.9, 121.8, 120.3, 60.2, 59.1, 34.3, 30.3,
14.2; IR (neat) ν 3632, 2960, 1706, 1624, 1485, 1434, 1262, 1129,
1011, 799 cm−1; mp 57−58 °C; HRMS (ESI) m/z: [M − H]− Calcd
for C34H38O3Br 573.2010, found: 573.2007.
Ethyl (2E,4Z)-6-(3-Bromophenyl)-6-(3,5-di-tert-butyl-4-hydroxy-
phenyl)-5-phenylhexa-2,4-dienoate (3c). Compound 3c (43 mg,
75% yield) was obtained as a yellowish solid following the general
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Scheme 3. Plausible Mechanism
Scheme 5. Applications of the Addition and Dienylation
Reaction
1
EtOAc = 20:1); H NMR (400 MHz, CDCl3) δ 7.56 (d, J = 8.0 Hz,
1H), 7.37−7.29 (m, 4H), 7.26−7.20 (m, 2H), 7.10−7.06 (m, 1H),
6.96−6.95 (m, 3H), 5.80−5.74 (m, 2H), 5.54 (s, 1H), 5.11 (s, 1H),
4.12 (q, J = 7.2 Hz, 2H), 1.38 (s, 18H), 1.22 (t, J = 7.2 Hz, 3H);
13C{H} NMR (100 MHz, CDCl3) δ 167.0, 153.7, 152.6, 144.5, 142.1,
140.3, 139.9, 136.0, 135.7, 133.0, 131.3, 129.9, 129.0, 128.8, 128.0,
127.1, 126.2, 125.6, 121.3, 60.3, 58.8, 34.3, 30.3, 14.3; IR (neat) ν
3626, 2960, 1711, 1624, 1434, 1259, 1093, 1022, 802, 700 cm−1; mp
135−136 °C; HRMS (ESI) m/z: [M − H]− Calcd for C34H38O3Br
573.2010, found: 573.2007.
Ethyl (2E,4Z)-6-(4-Chlorophenyl)-6-(3,5-ditert-butyl-4-hydroxy-
phenyl)-5-phenylhexa-2,4-dienoate (3e). Compound 3e (39 mg,
73% yield) was obtained as a yellow solid following the general
procedure from 1e (0.1 mmol) and 2a (0.12 mmol). Rf = 0.5 (PE/
EtOAc = 20:1); 1H NMR (400 MHz, CDCl3) δ 7.31−7.24 (m, 6H),
7.13−7.09 (m, 4H), 6.89 (s, 2H), 5.93 (d, J = 11.6 Hz, 1H), 5.80 (d, J
= 15.2 Hz, 1H), 5.15 (s, 1H), 5.12 (s, 1H), 4.13 (q, J = 7.2, 2H), 1.37
(s, 18H), 1.22 (t, J = 7.2 Hz, 3H); 13C{H} NMR (100 MHz, CDCl3)
δ 167.1, 154.8, 152.5, 141.8, 140.7, 139.8, 135.7, 132.2, 131.0, 130.8,
128.8, 128.4, 128.24, 128.17, 127.8, 125.9, 121.8, 60.2, 59.0, 34.3,
30.3, 14.2; IR (neat) ν 3635, 2963, 1706, 1624, 1488, 1434, 1262,
1129, 1093, 1016, 799, 703 cm−1; mp 50−51 °C; HRMS (ESI) m/z:
[M − H]− Calcd for C34H38O3Cl 529.2515, found: 529.2513.
Ethyl (2E,4Z)-6-(3,5-Di-tert-butyl-4-hydroxyphenyl)-6-(4-fluoro-
phenyl)-5-phenylhexa-2,4-dienoate (3f). Compound 3f (43 mg,
84% yield) was obtained as a yellow solid following the general
procedure from 1f (0.1 mmol) and 2a (0.12 mmol). Rf = 0.4 (PE/
EtOAc = 20:1); 1H NMR (400 MHz, CDCl3) δ 7.32−7.25 (m, 4H),
7.15−7.10 (m, 4H), 6.99−6.95 (m, 2H), 6.89 (s, 2H), 5.94 (d, J =
11.6 Hz, 1H), 5.80 (d, J = 15.2 Hz, 1H), 5.16 (s, 1H), 5.11 (s, 1H),
4.12 (q, J = 7.2 Hz, 2H), 1.37 (s, 18H), 1.23 (t, J = 7.2 Hz, 3H);
13C{H} NMR (100 MHz, CDCl3) δ 167.2, 161.5 (d, J = 243.6 Hz),
Scheme 4. Mechanism Study by Deuterium Labelling and
Control Experiment
procedure from 1c (0.1 mmol) and 2a (0.12 mmol). Rf = 0.4 (PE/
EtOAc = 20:1); 1H NMR (400 MHz, CDCl3) δ 7.33−7.27 (m, 6H),
7.17−7.09 (m, 4H), 6.89 (s, 2H), 5.94 (d, J = 11.6 Hz, 1H), 5.82 (d, J
= 15.2 Hz, 1H), 5.13 (s, 2H), 4.12 (q, J = 7.2 Hz, 2H), 1.37 (s, 18H),
1.22 (t, J = 7.2 Hz, 3H); 13C{H} NMR (100 MHz, CDCl3) δ 167.1,
154.5, 152.5, 144.5, 141.7, 139.8, 135.7, 132.5, 130.7, 129.8, 129.6,
128.8, 128.4, 128.2, 128.0, 127.8, 126.0, 122.5, 121.9, 60.2, 59.3, 34.3,
30.3, 14.2; IR (neat) ν 3632, 2960, 1711, 1624, 1471, 1434, 1262,
1132, 1028, 799, 703 cm−1; mp 55−56 °C; HRMS (ESI) m/z: [M −
H]− Calcd for C34H38O3Br 573.2010, found: 573.2008.
155.2, 152.4, 141.9, 140.0, 137.8 (d, J = 3.3 Hz), 135.7, 131.4, 130.9
(d, J = 7.9 Hz), 128.8, 128.1, 127.7, 125.9, 121.7, 115.1 (d, J = 21.0
Hz), 60.1, 58.9, 34.3, 30.3, 14.2; 19F{H} NMR (376 MHz, CDCl3) δ
−116.43 to −116.50 (m); IR (neat) ν 3638, 2957, 1706, 1624, 1505,
1434, 1367, 1268, 1228, 1132, 988, 844, 700 cm−1; mp 54−55 °C;
HRMS (ESI) m/z: [M − H]− Calcd for C34H38O3F 513.2811, found:
513.2809.
Ethyl (2E,4Z)-6-(3,5-Di-tert-butyl-4-hydroxyphenyl)-5-phenyl-6-
(p-tolyl)hexa-2,4-dienoate (3g). Compound 3g (39 mg, 78% yield)
was obtained as a yellow solid following the general procedure from
1g (0.1 mmol) and 2a (0.12 mmol). Rf = 0.4 (PE/EtOAc = 20:1); 1H
NMR (400 MHz, CDCl3) δ 7.32−7.23 (m, 4H), 7.14−7.04 (m, 6H),
6.92 (s, 2H), 5.97 (d, J = 11.6 Hz, 1H), 5.79 (d, J = 15.2 Hz, 1H),
5.13 (s, 1H), 5.08 (s, 1H), 4.12 (q, J = 7.2 Hz, 2H), 2.32 (s, 3H), 1.37
Ethyl (2E,4Z)-6-(2-Bromophenyl)-6-(3,5-di-tert-butyl-4-hydroxy-
phenyl)-5-phenylhexa-2,4-dienoate (3d). Compound 3d (36 mg,
64% yield) was obtained as a yellow solid following the general
procedure from 1d (0.1 mmol) and 2a (0.12 mmol). Rf = 0.5 (PE/
8594
https://doi.org/10.1021/acs.joc.1c00226
J. Org. Chem. 2021, 86, 8590−8599

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(s, 18H), 1.22 (t, J = 7.2 Hz, 3H); 13C{H} NMR (100 MHz, CDCl3)
δ 167.3, 155.7, 152.3, 142.1, 140.3, 139.1, 135.9, 135.4, 131.6, 129.3,
129.0, 128.8, 128.0, 127.9, 127.6, 126.0, 121.3, 60.1, 59.4, 34.3, 30.3,
21.0, 14.2; IR (neat) ν 3632, 2957, 1706, 1624, 1434, 1268, 1166,
1132, 1033, 991, 700 cm−1; mp 60−62 °C; HRMS (ESI) m/z: [M −
H]− Calcd for C35H41O3 509.3061; Found 509.3058.
(dd, J1 = 3.2 Hz, J2 = 5.2, Hz, 1H), 6.77 (dt, J1 = 1.2 Hz, J2 = 3.6 Hz,
1H), 6.20 (d, J = 11.6 Hz, 1H), 5.87 (d, J = 15.6 Hz, 1H), 5.31 (s,
1H), 5.12 (s, 1H), 4.13 (q, J = 7.2 Hz, 2H), 1.38 (s, 18H), 1.22 (t, J =
7.2 Hz, 3H); 13C{H} NMR (100 MHz, CDCl3) δ 167.1, 155.0, 152.7,
146.4, 141.9, 139.5, 135.6, 131.4, 129.0, 128.0, 127.7, 127.2, 126.6,
126.4, 125.5, 124.6, 121.9, 60.1, 54.9, 34.3, 30.3, 14.2; IR (neat) ν
3629, 2957, 1706, 1624, 1434, 1268, 1132, 988, 700 cm−1; mp 57−59
°C; HRMS (ESI) m/z: [M − H]− Calcd for C32H37O3S 501.2463,
found: 501.2466.
Ethyl (2E,4Z)-6-(3,5-Di-tert-butyl-4-hydroxyphenyl)-5-phenyl-6-
(pyridin-3-yl)hexa-2,4-dienoate (3m). Compound 3m (30 mg, 61%
yield) was obtained as a yellow solid following the general procedure
from 1m (0.1 mmol) and 2a (0.12 mmol). Rf = 0.6 (PE/EtOAc =
20:1); 1H NMR (400 MHz, CDCl3) δ 8.45 (brs, 2H), 7.50 (d, J = 8.0
Hz, 1H), 7.31−7.23 (m, 5H), 7.14−7.12 (m, 2H), 6.91 (s, 2H), 5.95
(d, J = 11.2 Hz, 1H), 5.81 (d, J = 15.2 Hz, 1H), 5.20 (s, 1H), 5.16 (s,
1H), 4.12 (q, J = 7.2 Hz, 2H), 1.38 (s, 18H), 1.22 (t, J = 7.2 Hz, 3H);
13C{H} NMR (100 MHz, CDCl3) δ 167.0, 153.9, 152.7, 150.4, 147.4,
Ethyl (2E,4Z)-6-(3,5-Di-tert-butyl-4-hydroxyphenyl)-6-(4-
methoxyphenyl)-5-phenylhexa-2,4-dienoate (3h). Compound 3h
(34 mg, 65% yield) was obtained as a yellowish solid following the
general procedure from 1h (0.1 mmol) and 2a (0.12 mmol). Rf = 0.5
1
(PE/EtOAc = 20:1); H NMR (400 MHz, CDCl3) δ 7.32−7.27 (m,
2H), 7.25−7.24 (m, 2H), 7.13−7.08 (m, 4H), 6.92 (s, 2H), 6.83 (d, J
= 8.8 Hz, 2H), 5.97 (d, J = 11.6 Hz, 1H), 5.80 (d, J = 15.2 Hz, 1H),
5.12 (s, 1H), 5.08 (s, 1H), 4.12 (q, J = 7.2 Hz, 2H), 3.79 (s, 3H), 1.37
(s, 18H), 1.22 (t, J = 7.2 Hz, 3H); 13C{H} NMR (100 MHz, CDCl3)
δ 167.3, 158.0, 155.9, 152.3, 142.1, 140.2, 135.5, 134.1, 131.8, 130.4,
128.8, 128.0, 127.8, 127.6, 126.0, 121.3, 113.6, 60.1, 58.9, 55.2, 34.3,
30.3, 14.2; IR (neat) ν 3629, 2958, 1708, 1623, 1509, 1434, 1367,
1303, 1249, 1174, 1132, 1035, 991, 701 cm−1; mp 58−59 °C; HRMS
(ESI) m/z: [M − H]− Calcd for C35H41O4 525.3010, found:
525.3004.
141.4, 139.5, 138.0, 137.1, 136.0, 130.1, 128.8, 128.6, 128.3, 127.9,
125.9, 123.3, 122.2, 60.2, 57.2, 34.3, 30.2, 14.2; IR (neat) ν 3632,
2958, 1708, 1625, 1434, 1367, 1305, 1267, 1172, 1132, 1027, 991,
768 cm−1; mp 65−66 °C; HRMS (ESI) m/z: [M − H]− Calcd for
C33H38O3 496.2857, found: 496.2853.
Ethyl (2E,4Z)-6-(3,5-Di-tert-butyl-4-hydroxyphenyl)-5-phenyl-6-
(3,4,5-trimethoxyphenyl)hexa-2,4-dienoate (3i). Compound 3i (33
mg, 57% yield) was obtained as a yellow solid following the general
procedure from 1i (0.1 mmol) and 2a (0.12 mmol). Rf = 0.3 (PE/
EtOAc = 20:1); 1H NMR (400 MHz, CDCl3) δ 7.32−7.25 (m, 4H),
7.12−7.09 (m, 2H), 6.94 (s, 2H), 6.39 (s, 2H), 6.01 (d, J = 11.6 Hz,
1H), 5.83 (d, J = 15.2 Hz, 1H), 5.11 (s, 1H), 5.08 (s, 1H), 4.13 (q, J =
7.2 Hz, 2H), 3.83 (s, 3H), 3.76 (s, 6H), 1.38 (s, 18H), 1.22 (t, J = 7.2
Hz, 3H); 13C{H} NMR (100 MHz, CDCl3) δ 167.2, 155.3, 152.9,
152.4, 142.0, 140.0, 137.5, 136.5, 135.6, 131.3, 128.9, 128.1, 127.9,
127.7, 125.9, 121.6, 60.9, 60.1, 59.9, 56.0, 34.3, 30.3, 14.2; IR (neat) ν
3646, 2954, 1714, 1624, 1587, 1505, 1454, 1262, 1234, 1127, 799
cm−1; mp 58−60 °C; HRMS (ESI) m/z: [M − H]− Calcd for
C37H45O6 585.3222, found: 585.3215.
Ethyl (2E,4Z)-6-(3,5-Di-tert-butyl-4-hydroxyphenyl)-5-phenyl-6-
(4-(trifluoromethyl)phenyl)hexa-2,4-dienoate (3j). Compound 3j
(46 mg, 83% yield) was obtained as a yellow solid following the
general procedure from 1j (0.1 mmol) and 2a (0.12 mmol). Rf = 0.4
(PE/EtOAc = 20:1); 1H NMR (400 MHz, CDCl3) δ 7.54 (d, J = 8.0
Hz, 2H), 7.32−7.25 (m, 6H), 7.14−7.12 (m, 2H), 6.90 (s, 2H), 5.94
(d, J = 11.2 Hz, 1H), 5.82 (d, J = 15.2 Hz, 1H), 5.24 (s, 1H), 5.14 (s,
1H), 4.13 (q, J = 7.2 Hz, 2H), 1.37 (s, 18H), 1.22 (t, J = 7.2 Hz, 3H);
13C{H} NMR (100 MHz, CDCl3) δ 167.1, 154.3, 152.6, 146.4, 141.6,
Ethyl (2E,4Z)-6-(3,5-Di-tert-butyl-4-hydroxyphenyl)-6-(naphtha-
len-2-yl)-5-phenylhexa-2,4-dienoate (3n). Compound 3n (28 mg,
52% yield) was obtained as a white solid following the general
procedure from 1n (0.1 mmol) and 2a (0.12 mmol). Rf = 0.6 (PE/
EtOAc = 20:1); 1H NMR (400 MHz, CDCl3) δ 7.83−7.74 (m, 3H),
7.56 (s, 1H), 7.46−7.44 (m, 2H), 7.40−7.33 (m, 2H), 7.30−7.24 (m,
3H), 7.19−7.17 (m, 2H), 6.99 (s, 2H), 6.04 (d, J = 11.6 Hz, 1H),
5.80 (d, J = 15.2 Hz, 1H), 5.35 (s, 1H), 5.12 (s, 1H), 4.13 (q, J = 7.2
Hz, 2H), 1.38 (s, 18H), 1.22 (t, J = 7.2 Hz, 3H); 13C{H} NMR (100
MHz, CDCl3) δ 167.2, 155.2, 152.4, 142.0, 140.2, 139.8, 135.6, 133.4,
132.2, 131.3, 128.8, 128.4, 128.1, 128.0, 127.9, 127.8, 127.7, 127.5,
126.1, 125.9, 125.6, 121.6, 60.1, 59.8, 34.3, 30.3, 14.2; IR (neat) ν
3629, 2954, 1706, 1624, 1434, 1268, 1129, 991, 737, 700 cm−1; mp
68−70 °C; HRMS (ESI) m/z: [M − H]− Calcd for C38H41O3
545.3061, found: 545.3059.
Ethyl (2E,4Z)-6-(4-Hydroxy-3,5-diisopropylphenyl)-5,6-diphenyl-
hexa-2,4-dienoate (3o). Compound 3o (17 mg, 37% yield) was
obtained as a yellow solid following the general procedure from 1o
1
(0.1 mmol) and 2a (0.12 mmol). Rf = 0.4 (PE/EtOAc = 20:1); H
NMR (400 MHz, CDCl3) δ 7.43−7.27 (m, 4H), 7.25−7.21 (m, 3H),
7.18−7.13 (m, 4H), 6.81 (s, 2H), 5.95 (d, J = 11.2 Hz, 1H), 5.79 (d, J
= 15.2 Hz, 1H), 5.20 (s, 1H), 4.69 (s, 1H), 4.11 (q, J = 7.2 Hz, 2H),
3.14−3.04 (m, 2H), 1.39 (s, 18H), 1.21 (t, J = 7.2 Hz, 3H), 1.18 (d, J
= 6.8 Hz, 12 H); 13C{H} NMR (100 MHz, CDCl3) δ 167.2, 155.3,
148.5, 142.1, 142.0, 140.1, 133.4, 132.7, 128.8, 128.3, 128.12, 128.09,
127.7, 126.5, 124.6, 121.5, 60.1, 59.5, 27.2, 22.73, 22.65, 14.2; IR
(neat) ν 3482, 2963, 1694, 1624, 1468, 1369, 1271, 1135, 1031, 991,
700 cm−1; mp 49−51 °C; HRMS (ESI) m/z: [M − H]− Calcd for
C32H35O3 467.2592, found: 467.2589.
139.7, 135.8, 130.5, 129.7, 128.8, 128.5, 128.2, 127.9, 125.2 (q, J = 4.8
Hz), 124.2 (q, J = 270.8 Hz), 122.1, 60.2, 59.4, 34.3, 30.2, 14.2;
19F{H} NMR (376 MHz, CDCl3) δ −62.19 (s); IR (neat) ν 3649,
2963, 1711, 1624, 1457, 1412, 1259, 1090, 1025, 802, 700 cm−1; mp
154−155 °C; HRMS (ESI) m/z: [M − H]− Calcd for C35H38O3F3
563.2773, found: 563.2780.
Ethyl (2E,4Z)-6-(3,5-Di-tert-butyl-4-hydroxyphenyl)-6-(4-nitro-
phenyl)-5-phenylhexa-2,4-dienoate (3k). Compound 3k (46 mg,
86% yield) was obtained as a yellow solid following the general
procedure from 1k (0.1 mmol) and 2a (0.12 mmol). Rf = 0.4 (PE/
Phenyl (2E,4Z)-6-(3,5-Di-tert-butyl-4-hydroxyphenyl)-5,6-
diphenylhexa-2,4-dienoate (3p). Compound 3p (19 mg, 33%
yield) was obtained as a yellowish solid following the general
procedure from 1a (0.1 mmol) and 2b (0.12 mmol). Rf = 0.4 (PE/
1
EtOAc = 20:1); H NMR (400 MHz, CDCl3) δ 8.14 (d, J = 8.8 Hz,
2H), 7.35 (d, J = 8.8 Hz, 2H), 7.32−7.27 (m, 4H), 7.15−7.13 (m,
2H), 6.90 (s, 2H), 5.94 (d, J = 11.6 Hz, 1H), 5.83 (d, J = 15.2 Hz,
1H), 5.29 (s, 1H), 5.17 (s, 1H), 4.13 (q, J = 7.2 Hz, 2H), 1.38 (s,
18H), 1.22 (t, J = 7.2 Hz, 3H); 13C{H} NMR (100 MHz, CDCl3) δ
167.0, 153.5, 152.8, 150.0, 146.6, 141.3, 139.4, 136.1, 130.2, 130.0,
128.8, 128.3, 128.1, 125.9, 123.6, 122.5, 60.2, 59.4, 34.4, 30.2, 14.2; IR
(neat) ν 3629, 2957, 1706, 1624, 1519, 1434, 1344, 1268, 1129, 855,
737, 700 cm−1; mp 63−65 °C; HRMS (ESI) m/z: [M − H]− Calcd
for C34H38 NO5 540.2756, found: 540.2753.
Ethyl (2E,4Z)-6-(3,5-Di-tert-butyl-4-hydroxyphenyl)-5-phenyl-6-
(thiophen-2-yl)hexa-2,4-dienoate (3l). Compound 3l (32 mg, 65%
yield) was obtained as a yellow solid following the general procedure
from 1l (0.1 mmol) and 2a (0.12 mmol). Rf = 0.7 (PE/EtOAc =
20:1); 1H NMR (400 MHz, CDCl3) δ 7.31−7.26 (m, 4H), 7.21 (dd,
J1 = 1.2 Hz, J2 = 5.2 Hz, 1H), 7.09−7.07 (m, 2H), 6.99 (s, 2H), 6.94
1
EtOAc = 20:1); H NMR (400 MHz, CDCl3) δ 7.49 (dd, J1 = 11.6
Hz, J2 = 15.2 Hz, 1H), 7.37−7.28 (m, 7H), 7.23−7.21 (m, 3H),
7.20−7.17 (m, 3H), 7.07 (d, J = 7.6 Hz, 2H), 6.97 (s, 2H), 6.09 (d, J
= 11.6 Hz, 1H), 6.01 (d, J = 15.2 Hz, 1H), 5.24 (s, 1H), 5.13 (s, 1H),
1.40 (s, 18H); 13C{H} NMR (100 MHz, CDCl3) δ 165.5, 156.9,
152.4, 150.8, 144.0, 141.9, 140.0, 135.6, 131.4, 129.4, 129.2, 128.8,
128.3, 128.1, 128.0, 127.8, 126.5, 126.1, 125.5, 121.6, 120.4, 59.8,
34.3, 30.3; IR (neat) ν 3630, 2957, 1726, 1621, 1590, 1491, 1434,
1231, 1194, 1160, 1115, 751, 700 cm−1; mp 49−51 °C; HRMS (ESI)
m/z: [M + Na]+ Calcd for C38H40O3Na 567.2875, found: 567.2871.
(2E,4Z)-6-(3,5-Di-tert-butyl-4-hydroxyphenyl)-N-methoxy-N-
methyl-5,6-diphenylhexa-2,4-dienamide (3q). Compound 3q (25
mg, 49% yield) was obtained as a yellow solid following the general
procedure from 1a (0.1 mmol) and 2c (0.12 mmol). Rf = 0.4 (PE/
8595
https://doi.org/10.1021/acs.joc.1c00226
J. Org. Chem. 2021, 86, 8590−8599

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
1
EtOAc = 20:1); H NMR (400 MHz, CDCl3) δ 7.36 (dd, J1 = 11.6
Ethyl (2E,4E)-5-((3,5-Di-tert-butyl-4-hydroxyphenyl)(4-
nitrophenyl)methyl)hepta-2,4-dienoate (3v). Compound 3v (26
mg, 53% yield) was obtained as a yellow solid following the general
procedure from 1a (0.1 mmol) and 2h (0.12 mmol). Rf = 0.4 (PE/
Hz, J2 = 15.2 Hz, 1H), 7.32−7.27 (m, 3H), 7.25−7.18 (m, 5H),
7.14−7.11 (m, 2H), 6.94 (s, 2H), 6.37 (d, J = 15.2 Hz, 1H), 6.04 (d, J
= 11.6 Hz, 1H), 5.18 (s, 1H), 5.09 (s, 1H), 3.67 (s, 3H), 3.19 (s, 3H),
1.37 (s, 18H); 13C{H} NMR (100 MHz, CDCl3) δ 167.4, 154.8,
152.3, 142.4, 141.0, 140.4, 135.4, 131.6, 129.5, 128.9, 128.5, 128.2,
128.1, 127.5, 126.3, 126.1, 119.1, 61.8, 59.7, 34.3, 32.3, 30.3; IR
(neat) ν 3536, 2957, 1646, 1604, 1432, 1381, 1234, 1093, 1002, 886,
737, 700 cm−1; mp 189−190 °C; HRMS (ESI) m/z: [M − H]− Calcd
for C34H40NO3 510.3014, found: 510.3007.
(2E,4Z)-6-(3,5-Di-tert-butyl-4-hydroxyphenyl)-1-morpholino-5,6-
diphenylhexa-2,4-dien-1-one (3r). Compound 3r (21 mg, 40%
yield) was obtained as a white solid following the general procedure
from 1a (0.1 mmol) and 2d (0.12 mmol). Rf = 0.4 (PE/EtOAc =
20:1); 1H NMR (400 MHz, CDCl3) δ 7.36−7.31 (m, 1H), 7.30−7.25
(m, 3H), 7.24−7.17 (m, 5H), 7.14−7.12 (m, 2H), 6.93 (s, 2H), 6.19
(d, J = 14.4 Hz, 1H), 5.96 (d, J = 11.6 Hz, 1H), 5.18 (s, 1H), 5.09 (s,
1H), 3.64 (brs, 5H), 3.61 (brs, 3H), 1.37 (s, 18H); 13C{H} NMR
(100 MHz, CDCl3) δ 165.8, 154.4, 152.3, 142.4, 140.7, 140.3, 135.4,
131.6, 129.5, 128.8, 128.4, 128.2, 128.1, 127.5, 126.3, 126.1, 119.8,
66.8, 59.7, 46.1, 42.2, 34.3, 30.3; IR (neat) ν 3629, 2957, 1638, 1598,
1434, 1268, 1231, 1115, 1036, 982, 703 cm−1; mp 98−100 °C;
HRMS (ESI) m/z: [M − H]− Calcd for C36H42NO3 536.3170, found:
536.3165.
Ethyl (2E,4Z)-6-(3,5-Di-tert-butyl-4-hydroxyphenyl)-5-(4-fluoro-
phenyl)-6-phenylhexa-2,4-dienoate (3s). Compound 3s (44 mg,
85% yield) was obtained as a yellow solid following the general
procedure from 1a (0.1 mmol) and 2e (0.12 mmol). Rf = 0.4 (PE/
EtOAc = 20:1); 1H NMR (400 MHz, CDCl3) δ 7.31−7.27 (m, 2H),
7.23−7.15 (m, 4H), 7.10−7.07 (m, 2H), 6.99−6.94 (m, 2H), 6.90 (s,
2H), 5.98 (d, J = 11.6 Hz, 1H), 5.80 (d, J = 15.2 Hz, 1H), 5.12 (s,
1H), 5.11 (s, 1H), 4.13 (q, J = 7.2 Hz, 2H), 1.37 (s, 18H), 1.22 (t, J =
7.2 Hz, 3H); 13C{H} NMR (100 MHz, CDCl3) δ 167.1, 162.2 (d, J =
245.6 Hz), 154.3, 152.4, 141.8, 141.6, 136.0 (d, J = 3.3 Hz), 135.6,
131.2, 130.5 (d, J = 8.0 Hz), 129.4, 128.32, 128.27, 126.5, 126.0,
121.8, 115.1 (d, J = 21.3 Hz), 60.2, 59.9, 34.3, 30.3, 14.2; 19F{H}
NMR (376 MHz, CDCl3) δ −114.17 to −114.09 (m); IR (neat) ν
3635, 2960, 1708, 1627, 1598, 1508, 1434, 1268, 1234, 1129, 1031,
844, 737, 700 cm−1; mp 53−55 °C; HRMS (ESI) m/z: [M − H]−
Calcd for C34H38O3F 513.2811, found: 513.2807.
1
EtOAc = 20:1); H NMR (400 MHz, CDCl3) δ 8.15 (d, J = 7.6 Hz,
2H), 7.35 (d, J = 8.0 Hz, 2H), 7.09−7.02 (m, 1H), 6.85 (s, 2H), 5.96
(d, J = 11.2 Hz, 1H), 5.85 (dt, J1 = 6.8 Hz, J2 = 14.8 Hz, 1H), 5.39 (s,
1H), 5.15 (s, 1H), 4.10 (q, J = 7.2 Hz, 2H), 2.21−2.13 (m, 2H), 1.37
(s, 18H), 1.09 (t, J = 7.2 Hz, 3H), 1.03 (t, J = 7.2 Hz, 3H); 13C{H}
NMR (100 MHz, CDCl3) δ 167.2, 152.6, 151.3, 146.4, 145.2, 141.7,
135.9, 131.3, 130.8, 129.8, 126.0, 125.8, 123.5, 60.4, 53.8, 34.3, 30.2,
26.0, 14.0, 12.9; IR (neat) ν 3629, 2960, 1703, 1593, 1519, 1434,
1344, 1208, 1155, 1014, 980, 855, 737 cm−1; mp 50−51 °C; HRMS
(ESI) m/z: [M − H]− Calcd for C30H38NO5 492.2756, found:
492.2762.
Ethyl (2E,4Z)-6-(3,5-Di-tert-butyl-4-hydroxyphenyl)-5-phenyl-6-
(1-tosyl-1H-indol-3-yl)hexa-2,4-dienoate (4a). Compound 4a (56
mg, 82% yield) was obtained as a white solid following the general
procedure from 1p (0.1 mmol) and 2a (0.12 mmol). Rf = 0.4 (PE/
1
EtOAc = 10:1); H NMR (400 MHz, CDCl3) δ 8.02 (d, J = 8.0 Hz,
1H), 7.63 (d, J = 8.4 Hz, 2H), 7.37 (d, J = 7.6 Hz, 1H), 7.33−7.28
(m, 5H), 7.21−7.18 (m, 3H), 7.15−7.13 (m, 2H), 6.96−6.95 (m,
3H), 5.88 (d, J = 11.2 Hz, 1H), 5.60 (d, J = 15.2 Hz, 1H), 5.15 (s,
1H), 5.14 (s, 1H), 4.12 (q, J = 7.2 Hz, 2H), 2.37 (s, 3H), 1.38 (s,
18H), 1.21 (d, J = 7.2 Hz, 3H); 13C{H} NMR (100 MHz, CDCl3) δ
167.1, 152.8, 152.3, 144.8, 141.6, 139.7, 135.9, 135.0, 130.4, 129.74,
129.71, 128.8, 128.2, 127.9, 127.4, 126.6, 126.2, 126.1, 125.4, 124.9,
123.4, 121.9, 120.2, 114.1, 60.1, 50.9, 34.3, 30.3, 21.5, 14.2; IR (neat)
ν 3629, 2957, 1706, 1624, 1598, 1443, 1432, 1372, 1268, 1169, 1129,
1093, 980, 807, 700 cm−1; mp 170−172 °C; HRMS (ESI) m/z: [M −
H]− Calcd for C43H45NO5S 688.3102, found: 688.3099.
Ethyl (2E,4Z)-6-(5-Chloro-1-tosyl-1H-indol-3-yl)-6-(3,5-di-tert-
butyl-4-hydroxyphenyl)-5-phenylhexa-2,4-dienoate (4b). Com-
pound 4b (56 mg, 78% yield) was obtained as a yellow solid
following the general procedure from 1q (0.1 mmol) and 2a (0.12
mmol). Rf = 0.4 (PE/EtOAc = 10:1); 1H NMR (400 MHz, CDCl3) δ
7.93 (d, J = 8.8 Hz, 1H), 7.60 (d, J = 8.4 Hz, 2H), 7.31−7.27 (m,
5H), 7.25−7.24 (m, 1H), 7.20 (d, J = 8.0 Hz, 2H), 7.14−7.12 (m,
2H), 7.00 (d, J = 1.2 Hz, 1H), 6.94 (s, 2H), 5.85 (d, J = 11.6 Hz, 1H),
5.63 (d, J = 15.2 Hz, 1H), 5.17 (s, 1H), 5.09 (s, 1H), 4.13 (q, J = 7.2
Hz, 2H), 2.38 (s, 3H), 1.38 (s, 18H), 1.22 (t, J = 7.2 Hz, 3H);
13C{H} NMR (100 MHz, CDCl3) δ 167.0, 152.9, 152.0, 145.1, 141.4,
Ethyl (2E,4Z)-6-(3,5-Di-tert-butyl-4-hydroxyphenyl)-5-(4-
methoxyphenyl)-6-phenylhexa-2,4-dienoate (3t). Compound 3t
(37 mg, 71% yield) was obtained as a yellow solid following the
general procedure from 1a (0.1 mmol) and 2f (0.12 mmol). Rf = 0.4
139.5, 136.0, 134.7, 134.2, 131.7, 129.9, 129.4, 129.3, 128.7, 128.3,
128.0, 127.5, 127.4, 126.6, 125.5, 125.4, 125.2, 122.2, 119.9, 115.1,
60.2, 50.7, 34.4, 30.3, 21.5, 14.2; IR (neat) ν 3626, 2957, 1711, 1621,
1432, 1265, 1172, 1118, 980, 807, 669 cm−1; mp 190−192 °C;
HRMS (ESI) m/z: [M − H]− Calcd for C43H45NO5SCl 722.2713,
found: 722.2711.
1
(PE/EtOAc = 20:1); H NMR (400 MHz, CDCl3) δ 7.34 (dd, J1 =
11.6 Hz, J2 = 15.2 Hz, 1H), 7.30−7.26 (m, 2H), 7.22−7.15 (m, 3H),
7.09−7.07 (m, 2H), 6.91 (s, 2H), 6.82−6.80 (m, 2H), 5.93 (d, J =
11.6 Hz, 1H), 5.78 (d, J = 15.2 Hz, 1H), 5.17 (s, 1H), 5.09 (s, 1H),
4.13 (q, J = 7.2 Hz, 2H), 3.78 (s, 3H), 1.37 (s, 18H), 1.23 (t, J = 7.2
Hz, 3H); 13C{H} NMR (100 MHz, CDCl3) δ 167.3, 159.1, 155.1,
152.3, 142.4, 142.3, 135.5, 132.5, 131.7, 130.1, 129.4, 128.2, 127.8,
126.4, 126.0, 121.0, 113.5, 60.1, 59.7, 55.2, 34.3, 30.3, 14.3; IR (neat)
ν 3632, 2957, 1703, 1621, 1508, 1434, 1248, 1175, 1129, 1031, 833,
737, 700 cm−1; mp 64−65 °C; HRMS (ESI) m/z: [M − H]− Calcd
for C35H41O4 525.3010, found: 525.3007.
Ethyl (2E,4E)-6-(3,5-Di-tert-butyl-4-hydroxyphenyl)-5-methyl-6-
(4-nitrophenyl)hexa-2,4-dienoate (3u). Compound 3u (27 mg,
58% yield) was obtained as a yellow solid following the general
procedure from 1a (0.1 mmol) and 2g (0.12 mmol). Rf = 0.4 (PE/
EtOAc = 20:1); 1H NMR (400 MHz, CDCl3) δ 8.17−8.13 (m, 2H),
7.36−7.33 (m, 2H), 7.10−7.03 (m, 1H), 6.84 (s, 2H), 5.94 (d, J =
11.2 Hz, 1H), 5.86−5.77 (m, 1H), 5.38 (s, 1H), 5.15 (s, 1H), 4.12−
4.07 (m, 2H), 1.82 (dd, J1 = 1.2 Hz, J2 = 6.8 Hz, 3H), 1.37 (s, 18H),
1.09 (t, J = 7.2 Hz, 3H); 13C{H} NMR (100 MHz, CDCl3) δ 167.2,
152.6, 151.2, 146.4, 141.6, 138.5, 135.9, 131.1, 130.8, 129.8, 128.4,
125.8, 123.5, 60.4, 53.8, 34.3, 30.2, 18.7, 14.0; IR (neat) ν 3629, 2957,
1711, 1519, 1432, 1347, 1211, 1158, 980, 703 cm−1; mp 55−56 °C;
HRMS (ESI) m/z: [M − H]− Calcd for C29H36NO5 478.2599, found:
478.2603.
Ethyl (2E,4Z)-6-(6-Bromo-1-tosyl-1H-indol-3-yl)-6-(3,5-di-tert-
butyl-4-hydroxyphenyl)-5-phenylhexa-2,4-dienoate (4c). Com-
pound 4c (65 mg, 85% yield) was obtained as a yellow solid
following the general procedure from 1r (0.1 mmol) and 2a (0.12
mmol). Rf = 0.4 (PE/EtOAc = 10:1); 1H NMR (400 MHz, CDCl3) δ
8.20 (d, J = 1.6 Hz, 1H), 7.63 (d, J = 8.4 Hz, 2H), 7.31−7.26 (m,
5H), 7.24−7.20 (m, 3H), 7.12−7.10 (m, 2H), 6.94−6.93 (m, 3H),
5.85 (d, J = 11.6 Hz, 1H), 5.62 (d, J = 15.2 Hz, 1H), 5.17 (s, 1H),
5.11 (s, 1H), 4.12 (q, J = 7.2 Hz, 2H), 2.39 (s, 3H), 1.38 (s, 18H),
1.22 (t, J = 7.2 Hz, 3H); 13C{H} NMR (100 MHz, CDCl3) δ 167.0,
152.8, 152.0, 145.2, 141.4, 139.5, 136.5, 135.9, 134.8, 129.9, 129.4,
129.2, 128.7, 128.3, 128.0, 127.5, 126.7, 126.6, 126.5, 125.9, 125.3,
122.2, 121.4, 118.6, 117.1, 60.2, 50.7, 34.3, 30.3, 21.6, 14.2; IR (neat)
ν 3629, 2954, 1703, 1624, 1432, 1372, 1265, 1172, 1129, 982, 807,
667 cm−1; mp 208−209 °C; HRMS (ESI) m/z: [M − H]− Calcd for
C43H45NO5Br 766.2207, found: 766.2202.
Ethyl (2E,4Z)-6-(4-Bromo-1-tosyl-1H-indol-3-yl)-6-(3,5-ditert-
butyl-4-hydroxyphenyl)-5-phenylhexa-2,4-dienoate (4d). Com-
pound 4d (51 mg, 67% yield) was obtained as a yellow solid
following the general procedure from 1s (0.1 mmol) and 2a (0.12
mmol). Rf = 0.4 (PE/EtOAc = 10:1); 1H NMR (400 MHz, CDCl3) δ
8.02 (d, J = 8.4 Hz, 1H), 7.60 (d, J = 8.0 Hz, 2H), 7.41−7.36 (m,
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Article
2H), 7.26−7.20 (m, 7H), 7.15−7.11 (m, 1H), 6.98−6.97 (m, 3H),
5.85 (s, 1H), 5.67 (d, J = 11.6 Hz, 1H), 5.52 (d, J = 15.2 Hz, 1H),
5.15 (s, 1H), 4.13 (q, J = 7.2 Hz, 2H), 2.39 (s, 3H), 1.40 (s, 18H),
1.22 (t, J = 7.1 Hz, 3H); 13C{H} NMR (100 MHz, CDCl3) δ 167.1,
153.4, 152.6, 145.3, 142.0, 139.4, 137.1, 135.8, 134.5, 130.5, 129.9,
129.3, 128.5, 128.4, 128.3, 128.0, 127.8, 127.2, 126.7, 126.2, 125.9,
125.6, 121.8, 114.7, 113.2, 60.1, 50.2, 34.3, 30.4, 21.6, 14.2; IR (neat)
ν 3629, 2954, 1709, 1624, 1593, 1454, 1373, 1304, 1265, 1172, 1130,
1093, 983, 807, 703 cm−1; mp 173−175 °C; HRMS (ESI) m/z: [M −
H]− Calcd for C43H45NO5SBr 766.2207, found: 766.2203.
1121, 1028, 802, 740, 703 cm−1; mp 161−162 °C; HRMS (ESI) m/z:
[M − H]− Calcd for C36H39NO4F 568.2869, found: 568.2866.
Ethyl (2E,4E)-5-(3-(3,5-Di-tert-butyl-4-hydroxyphenyl)-5-me-
thoxy-1-methyl-2-oxoindolin-3-yl)-5-phenylpenta-2,4-dienoate
(5d). Compound 5d (31 mg, 53% yield) was obtained as a yellow
solid following the general procedure from 1x (0.1 mmol) and 2a
1
(0.12 mmol). Rf = 0.3 (PE/EtOAc = 8:1); H NMR (400 MHz,
CDCl3) δ 7.39 (s, 2H), 7.20−7.14 (m, 3H), 7.02−6.95 (m, 1H),
6.84−6.82 (m, 1H), 6.69−6.65 (m, 3H), 6.52−6.47 (m, 2H), 5.86 (d,
J = 15.2 Hz, 1H), 5.23 (s, 1H), 4.09 (q, J = 7.2 Hz, 2H), 2.99 (s, 3H),
1.40 (s, 18H), 1.20 (t, J = 7.2 Hz, 3H); 13C{H} NMR (100 MHz,
CDCl3) δ 175.8, 166.9, 155.4, 153.4, 152.4, 141.7, 137.5, 136.9, 135.4,
130.8, 129.7, 128.4, 127.7, 127.6, 127.3, 126.0, 122.4, 114.0, 113.2,
108.6, 64.3, 60.2, 55.9, 34.5, 30.3, 26.4, 14.2; IR (neat) ν 3632, 2960,
1706, 1624, 1499, 1434, 1364, 1265, 1132, 1031, 805, 737, 703 cm−1;
mp 160−162 °C; HRMS (ESI) m/z: [M − H]− Calcd for
C37H42NO5 580.3069, found: 580.3066.
Ethyl (2E,4E)-5-(3-(3,5-Di-tert-butyl-4-hydroxyphenyl)-1,5-di-
methyl-2-oxoindolin-3-yl)-5-phenylpenta-2,4-dienoate (5e). Com-
pound 5e (24 mg, 42% yield) was obtained as a yellowish solid
following the general procedure from 1y (0.1 mmol) and 2a (0.12
mmol). Rf = 0.5 (PE/EtOAc = 8:1); 1H NMR (400 MHz, CDCl3) δ
7.39 (s, 2H), 7.21−7.08 (m, 4H), 7.02−6.95 (m, 1H), 6.82 (s, 1H),
6.69−6.61 (m, 3H), 6.40 (d, J = 11.2 Hz, 1H), 5.84 (d, J = 15.2 Hz,
1H), 5.22 (s, 1H), 4.09 (q, J = 7.2 Hz, 2H), 2.95 (s, 3H), 2.32 (s,
3H), 1.39 (s, 18H), 1.20 (t, J = 7.2 Hz, 3H); 13C{H} NMR (100
MHz, CDCl3) δ 176.0, 167.0, 153.3, 153.1, 141.7, 141.5, 136.9, 135.2,
131.4, 129.7, 129.6, 128.8, 128.4, 127.7, 127.5, 127.4, 127.3, 126.1,
122.1, 107.9, 64.1, 60.2, 34.5, 30.2, 26.3, 21.2, 14.2; IR (neat) ν 3632,
2954, 1706, 1624, 1499, 1434, 1354, 1268, 1132, 1033, 988, 807, 737,
703 cm−1; mp 158−159 °C; HRMS (ESI) m/z: [M − H]− Calcd for
C37H42NO4 564.3119, found: 564.3117.
Ethyl (2E,4E)-5-(3-(3,5-Di-tert-butyl-4-hydroxyphenyl)-1,7-di-
methyl-2-oxoindolin-3-yl)-5-phenylpenta-2,4-dienoate (5f). Com-
pound 5f (26 mg, 47% yield) was obtained as a yellow solid following
the general procedure from 1z (0.1 mmol) and 2a (0.12 mmol). Rf =
0.4 (PE/EtOAc = 8:1); 1H NMR (400 MHz, CDCl3) δ 7.37 (s, 2H),
7.19−7.13 (m, 3H), 7.00−6.88 (m, 5H), 6.70 (s, 1H), 6.36 (d, J =
11.6 Hz, 1H), 5.82 (d, J = 15.6 Hz, 1H), 5.22 (s, 1H), 4.09 (q, J = 6.8
Hz, 2H), 3.24 (s, 3H), 2.48 (s, 3H), 1.39 (s, 18H), 1.19 (t, J = 6.8 Hz,
3H); 13C{H} NMR (100 MHz, CDCl3) δ 176.9, 167.0, 153.3, 141.7,
136.9, 135.2, 132.3, 130.2, 129.6, 128.6, 127.7, 127.5, 126.3, 124.7,
122.1, 119.7, 63.6, 60.1, 34.5, 30.3, 30.2, 19.2, 14.2; IR (neat) ν 3581,
2960, 1706, 1627, 1457, 1437, 1268, 1115, 1011, 799, 703 cm−1; mp
163−164 °C; HRMS (ESI) m/z: [M − H]− Calcd for C37H42NO4
564.3119, found: 564.3116.
Ethyl (2E,4Z)-6-(3,5-Di-tert-butyl-4-hydroxyphenyl)-6-(1-methyl-
1H-indol-3-yl)-5-phenylhexa-2,4-dienoate (4e). Compound 4e (30
mg, 56% yield) was obtained as a yellow solid following the general
procedure from 1t (0.1 mmol) and 2a (0.12 mmol). Rf = 0.4 (PE/
1
EtOAc = 10:1); H NMR (400 MHz, CDCl3) δ 7.53 (d, J = 8.0 Hz,
1H), 7.35−7.28 (m, 5H), 7.23−7.22 (m, 1H), 7.16−7.14 (m, 2H),
7.11−7.08 (m, 1H), 7.04 (s, 2H), 6.46 (s, 1H), 6.17 (d, J = 11.6 Hz,
1H), 5.73 (d, J = 15.2 Hz, 1H), 5.26 (s, 1H), 5.08 (s, 1H), 4.10 (q, J =
7.2 Hz, 2H), 3.72 (s, 3H), 1.38 (s, 18H), 1.20 (t, J = 7.2 Hz, 3H);
13C{H} NMR (100 MHz, CDCl3) δ 167.4, 154.8, 152.3, 142.4, 140.5,
137.4, 135.5, 131.6, 128.91, 128.87, 128.0, 127.5, 127.3, 126.7, 125.6,
121.6, 121.0, 119.7, 118.9, 117.1, 109.2, 60.0, 51.6, 34.3, 32.8, 30.4,
14.2; IR (neat) ν 3629, 2954, 1703, 1621, 1471, 1432, 1367, 1265,
1169, 1132, 1031, 740, 700 cm−1; mp 63−64 °C; HRMS (ESI) m/z:
[M − H]− Calcd for C37H42NO3 548.3170, found: 548.3163.
Ethyl (2E,4E)-5-(3-(3,5-Di-tert-butyl-4-hydroxyphenyl)-1-methyl-
2-oxoindolin-3-yl)-5-phenylpenta-2,4-dienoate (5a). Compound 5a
(29 mg, 52% yield) was obtained as a yellow solid following the
general procedure from 1u (0.1 mmol) and 2a (0.12 mmol). Rf = 0.4
1
(PE/EtOAc = 8:1); H NMR (400 MHz, CDCl3) δ 7.40 (s, 2H),
7.32−7.27 (m, 1H), 7.22−7.17 (m, 1H), 7.14−7.10 (m, 2H), 7.07−
7.04 (m, 1H), 7.01−6.97 (m, 2H), 6.74 (d, J = 8.0 Hz, 1H), 6.68 (brs,
1H), 6.43 (d, J = 11.6 Hz, 1H), 5.85 (d, J = 15.6 Hz, 1H), 5.23 (s,
1H), 4.09 (q, J = 7.2 Hz, 2H), 2.99 (s, 3H), 1.39 (s, 18H), 1.19 (t, J =
7.2 Hz, 3H); 13C{H} NMR (100 MHz, CDCl3) δ 176.1, 166.9, 153.4,
152.7, 143.8, 141.6, 136.8, 135.4, 129.8, 128.6, 127.7, 127.5, 127.3,
126.7, 126.1, 122.3, 122.0, 108.3, 64.1, 60.2, 34.5, 30.3, 26.3, 14.2; IR
(neat) ν 3629, 2957, 1708, 1624, 1607, 1488, 1471, 1432, 1367, 1271,
1132, 1028, 740, 703 cm−1; mp 163−165 °C; HRMS (ESI) m/z: [M
− H]− Calcd for C36H40NO4 550.2963, found: 550.2962.
Ethyl (2E,4E)-5-(5-Chloro-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-
1-methyl-2-oxoindolin-3-yl)-5-phenylpenta-2,4-dienoate (5b).
Compound 5b (29 mg, 50% yield) was obtained as a yellow solid
following the general procedure from 1v (0.1 mmol) and 2a (0.12
mmol). Rf = 0.6 (PE/EtOAc = 8:1); 1H NMR (400 MHz, CDCl3) δ
7.35 (s, 2H), 7.26−7.16 (m, 4H), 7.00−6.94 (m, 2H), 6.70−6.65 (m,
3H), 6.42 (d, J = 11.6 Hz, 1H), 5.86 (d, J = 15.6 Hz, 1H), 5.26 (s,
1H), 4.10 (q, J = 6.8 Hz, 2H), 2.98 (s, 3H), 1.40 (s, 18H), 1.20 (t, J =
6.8 Hz, 3H); 13C{H} NMR (100 MHz, CDCl3) δ 175.7, 166.8, 153.6,
151.8, 142.3, 141.3, 136.5, 135.5, 131.5, 129.6, 129.0, 128.5, 127.9,
127.7, 127.4, 126.9, 126.6, 125.9, 122.8, 109.1, 64.1, 60.2, 34.5, 30.2,
26.4, 14.3; IR (neat) ν 3629, 2957, 1708, 1624, 1604, 1485, 1432,
1262, 1095, 1025, 807, 737, 700 cm−1; mp 167−168 °C; HRMS
(ESI) m/z: [M − H]− Calcd for C36H39NO4Cl 584.2573, found:
584.2572.
Ethyl (2E,4Z,7E)-6-(3,5-Di-tert-butyl-4-hydroxyphenyl)-5,8-di-
phenylocta-2,4,7-trienoate (9). Compound 9 (20 mg, 38% yield)
was obtained as a yellow solid following the general procedure from 7
1
(0.1 mmol) and 2a (0.12 mmol). Rf = 0.5 (PE/EtOAc = 20:1); H
NMR (400 MHz, CDCl3) δ 7.38−7.36 (m, 2H), 7.33−7.27 (m, 5H),
7.24−7.21 (m, 2H), 7.05−7.03 (m, 2H), 6.95 (s, 2H), 6.50 (dd, J1 =
7.6 Hz, J2 = 16.0 Hz, 1H), 6.41 (d, J = 15.6 Hz, 1H), 6.34 (d, J = 11.2
Hz, 1H), 5.91 (d, J = 15.6 Hz, 1H), 5.09 (s, 1H), 4.55 (d, J = 7.2 Hz,
1H), 4.13 (q, J = 7.2 Hz, 2H), 1.38 (s, 18H), 1.23 (t, J = 7.2 Hz, 3H);
13C{H} NMR (100 MHz, CDCl3) δ 167.2, 155.0, 152.5, 142.1, 139.3,
137.4, 135.7, 131.5, 131.3, 131.1, 129.0, 128.5, 128.0, 127.6, 127.3,
126.33, 126.25, 125.1, 121.4, 60.1, 57.1, 34.3, 30.3, 14.2; IR (neat) ν
3626, 2960, 2923, 1714, 1454, 1361, 1262, 1180, 1025, 802, 745, 697
cm−1; mp 50−52 °C; HRMS (ESI) m/z: [M − H]− Calcd for
C36H41O3 521.3061, found: 521.3060.
Ethyl (2E,4E)-5-(3-(3,5-Di-tert-butyl-4-hydroxyphenyl)-5-fluoro-
1-methyl-2-oxoindolin-3-yl)-5-phenylpenta-2,4-dienoate (5c).
Compound 5c (27 mg, 47% yield) was obtained as a yellow solid
following the general procedure from 1w (0.1 mmol) and 2a (0.12
mmol). Rf = 0.6 (PE/EtOAc = 8:1); 1H NMR (400 MHz, CDCl3) δ
7.35 (s, 2H), 7.28−7.25 (m, 1H), 7.21 (d, J = 7.2 Hz, 1H), 7.16 (t, J =
7.2 Hz, 2H), 7.00−6.94 (m, 2H), 6.70−6.65 (m, 3H), 6.42 (d, J =
11.2 Hz, 1H), 5.86 (d, J = 15.6 Hz, 1H), 5.26 (s, 1H), 4.10 (q, J = 7.2
Hz, 2H), 3.00 (s, 3H), 1.40 (s, 18H), 1.20 (t, J = 7.2 Hz, 3H);
13C{H} NMR (100 MHz, CDCl3) δ 175.8, 166.8, 158.7 (d, J = 239.4
Diethyl (2E,4Z)-6-(3,5-Di-tert-butyl-4-hydroxyphenyl)-5-phenyl-
hepta-2,4-dienedioate (10). Compound 10 (20 mg, 38% yield)
was obtained as a white solid following the general procedure from 8
1
(0.1 mmol) and 2a (0.12 mmol). Rf = 0.4 (PE/EtOAc = 12:1); H
NMR (400 MHz, CDCl3) δ 7.35−7.29 (m, 3H), 7.24−7.20 (m, 1H),
7.14−7.12 (m, 2H), 7.06 (s, 2H), 6.23 (d, J = 11.2 Hz, 1H), 5.87 (d, J
= 15.2 Hz, 1H), 5.18 (s, 1H), 4.71 (s, 1H), 4.15−4.04 (m, 4H), 1.40
(s, 18H), 1.22 (t, J = 7.2 Hz, 3H), 1.15 (t, J = 7.2 Hz, 3H); 13C{H}
NMR (100 MHz, CDCl3) δ 171.7, 167.0, 153.2, 149.8, 141.5, 138.5,
Hz), 153.5, 151.7, 141.3, 139.8, 136.5, 135.5, 131.5 (d, J = 7.6 Hz),
129.6, 128.9, 127.9, 127.7, 126.8, 125.8, 122.7, 114.9 (d, J = 23.3 Hz),
114.5 (d, J = 25.2 Hz), 108.6 (d, J = 7.7 Hz), 64.3, 60.2, 34.5, 30.2,
26.4, 14.2; 19F{H} NMR (376 MHz, CDCl3) δ −120.54 to −120.59
(m); IR (neat) ν 3635, 2960, 1708, 1624, 1194, 1437, 1367, 1262,
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135.8, 129.0, 128.1, 127.9, 127.2, 126.2, 125.8, 122.4, 61.0, 60.2, 59.7,
34.3, 30.2, 14.2, 14.0; IR (neat) ν 3629, 2957, 1731, 1627, 1434,
1367, 1268, 1169, 1132, 1031, 988, 884, 768, 700 cm−1; mp 68−69
°C; HRMS (ESI) m/z: [M − H]− Calcd for C31H39O5 491.2803,
found: 491.2809.
Laboratory of Chemical Genomics, Peking University
Shenzhen Graduate School, Shenzhen 518055, Guangdong,
China; orcid.org/0000-0002-3737-6621;
Email: wangde@ouc.edu.cn
General Procedure for the Synthesis of 3a Using Allenoate
6. Compound para-quinone methide 1a (0.1 mmol), PnBu3 (0.03
mmol) and anhydrous toluene (1.0 mL) were added into a preheated
Schlenk tube at room temperature under nitrogen atmosphere, then
allenoate 6 (0.12 mmol) was added to the above mixture under
nitrogen protection. The reaction mixture was stirred at this
temperature for 12 h (TLC monitored). The reaction mixture was
then concentrated on a rotary evaporator under reduce pressure and
the residue was subjected to purification by column chromatography
(PE/EtOAc = 100/1) to afford the corresponding product 3a.
Scale-up Procedure for the Synthesis of 4a. Compound para-
quinone methide 1p (1.0 mmol), alkyne 2a (1.2 mmol), o-NO2BzOH
(0.2 mmol) and toluene (10.0 mL) sequentially under dry nitrogen
atmosphere, then PnBu3 (0.3 mmol) was added and the mixture were
stirred for 12 h at 70 °C in an oil bath. Then water (10 mL) was
added to the reaction mixture and extracted with ethyl ether (10 mL
× 2). The organic layer was dried over with anhydrous Na2SO4 and
filtered. The solvent was removed under reduced pressure and the
residue were purified by column chromatography on silica gel (PE/
EtOAc = 10:1, Rf = 0.4), affording the corresponding products 4a in
76% yield (524 mg, >20:1 dr).
Authors
Zefeng Song − Molecular Synthesis Center, Key Laboratory of
Marine Drugs, Ministry of Education, School of Medicine and
Pharmacy, Ocean University of China, Qingdao 266071,
Shandong Province, China
Weijia Wang − Molecular Synthesis Center, Key Laboratory of
Marine Drugs, Ministry of Education, School of Medicine and
Pharmacy, Ocean University of China, Qingdao 266071,
Shandong Province, China
Zhixin Liu − Molecular Synthesis Center, Key Laboratory of
Marine Drugs, Ministry of Education, School of Medicine and
Pharmacy, Ocean University of China, Qingdao 266071,
Shandong Province, China
Yue Lu − Molecular Synthesis Center, Key Laboratory of
Marine Drugs, Ministry of Education, School of Medicine and
Pharmacy, Ocean University of China, Qingdao 266071,
Shandong Province, China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00226
General Procedure for the Deuterium Labeling Synthesis of
3l-D. p-QM 1l (0.1 mmol), 2-nitrobenzoic acid (0.02 mmol), and
anhydrous toluene (1.0 mL) were added into a dry Schlenk tube, and
then alkynoate 2a (0.15 mmol), D2O (1.0 mmol, 10 equiv), and
PnBu3 (0.03 mmol) were added subsequently under dry nitrogen
atmosphere. The reaction mixture was stirred at 70 °C for 12 h in an
oil bath (TLC monitored). The reaction mixture was then
concentrated on a rotary evaporator under reduced pressure and
the residue was subjected to purification by column chromatography
(PE/EtOAc = 100/1−20/1) to afford the corresponding product 3l-
Author Contributions
#Z.S. and W.W. contributed equally to this work.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
1
D as a yellow solid. H NMR (400 MHz, CDCl3) δ 7.31−7.25 (m,
We thank the Fundamental Research Funds for the Central
Universities in China (861801013177, 841912005, and
842064004) and NSFC (nos. 81991522, U1706213, and
81973232) for financial support. D.W. thanks Dr. X.-H. Miao
(Westlake University) for X-ray structural analysis.
3.58H, 42%D), 7.21 (dd, J1 = 1.2 Hz, J2 = 5.2 Hz, 1H), 7.09−7.07 (m,
2H), 6.98 (s, 2H), 6.94 (dd, J1 = 3.6 Hz, J2 = 5.2, Hz, 1H), 6.77 (dt, J1
= 1.2 Hz, J2 = 3.6 Hz, 1H), 6.20−6.17 (m, 0.58H, 42%D), 5.88−5.84
(m, 0.23H, 77%D), 5.30 (s, 1H), 5.12 (s, 1H, 100%D), 4.13 (q, J =
7.2 Hz, 2H), 1.38 (s, 18H), 1.22 (t, J = 7.2 Hz, 3H).
REFERENCES
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00226.
■
■
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AUTHOR INFORMATION
Corresponding Author
■
De Wang − Molecular Synthesis Center, Key Laboratory of
Marine Drugs, Ministry of Education, School of Medicine and
Pharmacy, Ocean University of China, Qingdao 266071,
Shandong Province, China; Laboratory for Marine Drugs
and Bioproducts & Open Studio for Druggability Research of
Marine Natural Products, Pilot National Laboratory for
Marine Science and Technology, Qingdao 266237, China;
State Key Laboratory of Chemical Oncogenomics, Key
8598
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