Organo-Catalyzed Regio- and Geometry-Specific Construction of β-Hydroxyl-α-vinyl Carboxylic Esters: Substrate Scope, Mechanistic Insights, and Applications

Article abstract of DOI:10.1021/acs.joc.8b01510

A green protocol has been developed for the synthesis of β-hydroxyl-α-vinyl carboxylic esters using aldehydes and α,β-unsaturated esters bearing an activated γ proton as starting materials under Morita-Baylis-Hillman (MBH) reaction conditions. Diverse β-hydroxyl-α-vinyl carboxylic esters have been synthesized regiospecifically in moderate to good yields with only E geometric selectivity. Other remarkable features include atom efficiency, environmental benignancy, and mild reaction conditions. Furthermore, the reaction products could be readily converted into tetrahydrofuran, dihydrofuran, and furan derivatives.

Full text of DOI:10.1021/acs.joc.8b01510

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Article
Organo-Catalyzed Regio- and Geometry-Specific
Construction of #-Hydroxyl-#-Vinyl Carboxylic Esters:
Substrate Scope, Mechanistic Insights and Applications
Yonghai Chai, Jinjin Zhou, Yanbin Wu, Yingle Feng, Panru
Wang, Yange Chen, Xinying Wang, Beibei Zhao, and Qi Zhang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01510 • Publication Date (Web): 08 Aug 2018
Downloaded from http://pubs.acs.org on August 8, 2018
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Organo-Catalyzed Regio- and Geometry-Specific Construction of -
Hydroxyl--Vinyl Carboxylic Esters: Substrate Scope, Mechanistic
Insights and Applications
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Yonghai Chai*a,b, JinJin Zhoua,b, Yanbin Wua,b, Yingle Fenga,b, Panru Wanga,b, Yange Chena,b, Xinying
Wanga,b, Beibei Zhaoa,b and Qi Zhangb*
a Key Laboratory of Applied Surface and Colloid Chemistry, MOE, Shaanxi Normal University, Xi’an, Shaanxi 710119, P.R.
China; b School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi’an, Shaanxi 710119, P.R. China
Supporting Information Placeholder
ABSTRACT: A green protocol has been developed for the synthesis of -hydroxyl--vinyl carboxylic esters using aldehydes and
,-unsaturated esters bearing an activated  proton as starting materials under Morita-Baylis-Hillman (MBH) reaction conditions.
Diverse -hydroxyl--vinyl carboxylic esters have been synthesized regio-specifically in moderate to good yields with only E geo-
metric selectivity. Other remarkable features include atom efficiency, environmental benignancy and mild reaction conditions. Fur-
thermore, the reaction products could be readily converted into tetrahydrofuran, dihydrofuran and furan derivatives.
transfer29 to produce int3, followed by -elimination to give the
final product 3 with liberation of the amine catalyst (Scheme 1).
◼
INTRODUCTION
-Hydroxyl--vinyl carboxylic esters, a kind of highly func-
tionalized compounds, contain several important structural mo-
tifs including homoallylic alcohols, ,-unsaturated esters and
-hydroxy esters. Thus, -hydroxyl--vinyl carboxylic esters
are versatile building blocks in organic synthesis, and their ap-
plications have been well documented in total synthesis as well
as in medicinal chemistry.1-7 In contrast to their wide use in syn-
thesis, few methods8-27 are available to prepare this kind of com-
pounds, mainly including allylation of aldehydes with -
(alkoxycarbonyl)-substituted allyl metal reagents8-18 and decon-
jugative aldol condensation of aldehydes or ketones with crotyl
derivatives19-24. Unfortunately, those processes often suffer
from some drawbacks such as harsh reaction conditions, poor
regioselectivity, and use of stoichiometric metal catalysts or
highly toxic reagents. Therefore, new facile and regioselective
synthetic approaches are still in great demand.
This novel protocol not only inherits the merits of MBH re-
action such as atom efficiency, environmental benignancy, mild
reaction conditions, etc, but also earns some new advantages
including the formation of two new stereogenic centers in one
step, and the wide applications in the rapid construction of di-
verse structural frameworks, especially tetrahydrofuran, dihy-
drofuran and furan derivatives.
Scheme 1. Possible mechanism for the reaction of aldehydes
and ,-unsaturated esters with an activated  proton under
MBH condition
With this goal in mind, we hypothesized that under the con-
dition of Morita-Baylis-Hillman (MBH) reaction28, usually cat-
alytic amounts of amine, ,-unsaturated ester with an activated
hydrogen in  position might react with aldehyde to form a new
type of compound, -hydroxyl--vinyl carboxylic ester, instead
of the common MBH product. The reaction involves reversible
conjugate addition of the nucleophilic amine catalyst to Michael
acceptor 1 to generate an -ammonium enolate int1, nucleo-
philic attack of int1 on the aldehyde 2 to form a second zwitter
ionic intermediate int2, and then intramolecular 1,5-proton
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the solution of 1a (1mmol) in solvent (2 mL), then the reaction mix-
◼
RESULTS AND DISCUSSION
b
c
d
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ture was stirred for 12 h; Isolated yield; dr = 1:1; 10 mol % of
To evaluate our hypothesis, commercially available ethyl (E)-
4-phenyl-2-butenoate (1a) and benzaldehyde (2a) were chosen
as the model substrates. Gratifyingly, when 1a and 2a were
treated with 20 mol% DBU in EtOH at rt, the expected product
(E)-ethyl-2-(hydroxy(phenyl)methyl)-4-phenylbut-3-enoate
(3aa) was obtained regiospecifically as a pair of diastereoiso-
mers (dr 1:1) in 48% yield (Table 1, entry 1). To improve the
yield, a series of tertiary amines and tertiary phosphines were
tested (Table 1, entries 2-8). Among these commonly used cat-
alysts for MBH reaction, DBU was proved to be the most effec-
tive one, which may be ascribed to the fact that the -ammo-
nium enolate intermediate int1 can gain the extra stability from
the conjugation of two nitrogens in DBU30. The solvent inves-
tigation showed that non-protic solvents, such as MeCN, THF
and 1,4-dioxane, resulted in lower yields (Table 1, entries 9-11)
while protic solvents, such as MeOH and EtOH, led to higher
yields (Table 1, entries 12-13). Considering cost as well as en-
vironmental benignancy, EtOH was chosen as the reaction sol-
vent. After further screening on the catalyst loading (Table 1,
entry 1d,e), the reaction temperature (Table 1, entries 13-15), and
the addition sequence (Table 1, entry 16), the optimal reaction
condition was determined to be DBU (20 mol%) in EtOH at 0
oC with certain addition sequence (Table 1, entry 16).
DBU was employed and the isolated yield is 41 %; e100 mol % of
f
DBU was employed and the isolated yield is 50 %; 1a (1mmol),
DBU (20 mol%), 2a (1 mmol) and EtOH (2 mL) were added suc-
cessively to a flask, then the reaction mixture was stirred at 0 oC for
12 h.
With the optimal condition in hand, we first explored the sub-
strate scope of the method using different aldehydes, and the
results are illustrated in Table 2. By treatment with DBU (20
9
o
mol%) in EtOH at 0 C, (E)-4-phenyl-2-butenoate (1a) could
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react with various aromatic/hetero aromatic/polycyclic aro-
matic aldehydes, giving the corresponding (E)--hydroxyl--
vinyl carboxylic esters in moderate to good yields (3aa-3ao).
Generally, aromatic aldehydes with substituents in ortho posi-
tion led to better outcomes than those with substituents in meta
or para position (3ad, 80% vs 3ae-3af, 47-71%), indicating that
the steric hindrance of the aryl ring has little effect on this reac-
tion. Meanwhile, electron-deficient aromatic aldehydes resulted
in higher yields than electron-rich ones (3ac, 3af, 3ah, 3aj, 48-
62% vs 3am, 32%), which revealed the coupling reaction has
great dependence on the electronic effect. Notably, the big dif-
ference between the yields of 3ab and 3ac further disclosed the
crucial role of the electron-withdrawing inductive effect in the
formation of -hydroxyl--vinyl carboxylic esters. Moreover,
the outcomes of ortho-halogenated products (3ad, 3ag, and 3al)
and para-halogenated products (3af, 3ah, and 3am) were also
in agreement with this disclosure. When using a mixture of THF
and water (50:1 v/v) instead of EtOH as the solvent, the cou-
pling of 1a with aliphatic aldehydes also proceeded smoothly
(3ap-3at). In contrast to the substituted aromatic aldehydes, the
steric hindrance of the aliphatic aldehydes has a significant im-
pact on this reaction (3ap-3ar, 72-78% vs 3as-3at, 45-66%).
Table 1. Optimization of Reaction Conditions of 1a with 2a
entrya
catalyst
DBUd,e
DABCO
Temp. solvent
Yield (%)b,c
1
2
3
4
5
6
rt
rt
rt
rt
rt
rt
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
48
0
Table 2. The substrate scope of the aldehydesa,b,c
PPh3
DBN
0
44
30
32
7
rt
EtOH
26
8
TMG
DBU
DBU
DBU
DBU
DBU
DBU
rt
EtOH
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27
9
rt
CH3CN
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11
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14
rt
1,4-dioxane 25
rt
THF
35
62
57
19
rt
MeOH
EtOH
EtOH
0 oC
reflux
15
DBU
DBU
-20 oC EtOH
0 oC
EtOH
47
65
16f
aFor aromatic/hetero aromatic/polycyclic aromatic aldehydes (2a-
2q), the reactions were carried out as follows: 1a (1mmol), DBU
(20 mol%), 2 (1 mmol) and EtOH (2 mL) were added successively
to a flask, then the reaction mixture was stirred at 0 oC for 12 h; for
aUnless otherwise noted, all reactions were carried out as follows:
2a (1 mmol) and catalyst (20 mol %) were added successively to
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aliphatic aldehydes, the reactions were carried out as follows: 1a
As mentioned above, -hydroxyl--vinyl carboxylic esters
are versatile building blocks in organic synthesis1-7 due to their
unique structural skeleton and densely functionalized nature.
For example, this kind of compounds could be applied to the
rapid construction of substituted tetrahydrofurans, dihydrofu-
rans and furans with multiple functional groups, which are priv-
ileged frameworks in many bioactive natural products, pharma-
ceuticals and materials31-32. As shown in Scheme 2, bromotetra-
hydrofuran (±)-4 could be easily installed from our product, (±)-
anti-3ap, by the treatment with 2 equiv of NBS at rt (Scheme 2,
a). When DBU was employed, the elimination reaction of (±)-4
occurred and produced dihydrofuran in high yields. With or
without the addition of H2O, 2,3- or 2,5-dihydrofuran could be
obtained respectively (Scheme 2, b and c). By oxidation of these
dihydrofurans, tri-substituted furan 7 was also prepared suc-
cessfully (Scheme 2, d).
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(1mmol), DBU (20 mol%), 2 (1 mmol), THF (2 mL) and H2O (27
uL) was added successively to a flask, then the reaction mixture
was stirred at 0 oC for 12 h; b Isolated yield; c Except 3as, all prod-
ucts were obtained as a pair of diastereoisomers and the dr value
d
was approximately equal to 1:1; The ratio of the four diastere-
omers was 2:1:1.3:1.7.
Next, we focused on the substrate scope in terms of various
,-unsaturated esters containing an aryl-activated  hydrogen.
As shown in Table 3, (E)-4-aryl-2-butenoate 1 with electron-
donating groups on the aryl ring was well tolerated under the
optimal condition and furnished the expected product in good
yields (3bb). Similarly, the electron-withdrawing groups such
as chloro and nitro, were compatible with this catalytic system,
affording the corresponding (E)--hydroxyl--vinyl carboxylic
esters in moderate yields (3cb-3ea). The coupling of 1f and 1g
with aldehyde 1b also worked well, indicating our approach
was applicable to polycyclic and hetero aromatic substrates (3fb
and 3gb). To further extend the generality of this reaction, (E)-
ethyl 4-phenyl-2-pentenoate 1h was employed and the results
proved that ,-unsaturated esters with an aryl substitute and
an alkyl substitute in  position were also suitable substrates for
the transformation (3ha and 3hb).
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Scheme 2. Further applications of -hydroxyl--vinyl car-
boxylic esters
Table 3. Substrate scope of the ,-unsaturated estera,b,c
(a) NBS (2 equiv)/DCM, rt, 92%; (b) DBU (1 equiv)/DCM, rt, 86%;
(c) DBU (1 equiv)/H2O (2 equiv)/DCM, reflux, 82% (from (±)-4)
and 89% (from (±)-5); (d) DDQ (2 equiv)/toluene, reflux, 95%
(from (±)-5) and 92% (from (±)-6).
To gain some insight into the reaction mechanism, a series of
experiments were conducted. In contrast to the commonly ac-
cepted mechanism for normal MBH reaction, which involves
intermolecular six-membered proton transfer in the assistance
of alcohol solvent33-34 or a second molecular of aldehyde35-36
,
there is a strong possibility that due to bearing an activated 
proton, the zwitter ionic intermediate int2 may undergo intra-
molecular 1,5-proton transfer via a chair-like six-membered
transition state to generate int329,37 (Scheme 1 and Scheme 3).
Scheme 3 Intramolecular 1,5-proton-transfer mechanism
aAll reactions were carried out as follows: 2 (1 mmol) and catalyst
(20 mol %) were added successively to the solution of 1 (1mmol)
in solvent (2 mL), then the reaction mixture was stirred for 12 h; b
Isolated yield; c In all cases, the products were obtained as a pair of
diastereoisomers and the dr value was approximately equal to 1:1.
Throughout the entire reaction, no normal MBH product was
observed38, indicating that the activated proton in  position in
int3 makes the direct intramolecular proton transfer much eas-
ier than intermolecular way. Furthermore, the decomposition of
classic MBH compound 8 under the above-mentioned standard
reaction conditions (Scheme 4, see SI, Figure S2) also illus-
trated that the formation of final -hydroxyl--vinyl carboxylic
esters is less likely through deconjugation of classic MBH prod-
ucts.
It is noteworthy that the coupling reaction demonstrated ex-
cellent regio- and geometry-specificity, and only -adducts
with (E) configuration were attained, with no  or (Z) isomers
observed. All obtained (E)--hydroxyl--vinyl carboxylic es-
ters consist of two diastereomers and the dr value was approx-
imately 1:1. The structure of the products was firmly estab-
lished by NMR experiments and single-crystal X-ray diffrac-
tion (XRD) analysis of two selected compounds 3ah and 3ad
(see SI, Figure S1 and Table S1).
Scheme 4. Investigation of the plausible key intermediate
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solution followed by heating. Flash column chromatography
was performed with silica gel 300-400 mesh.
1
2
3
Preparation of substrates ,-unsaturated esters.
However, due to the basic nature of DBU, this reaction may
occur via another possible mechanism as depicted in Scheme 5.
DBU serves as a base to abstract  proton, yielding the enolate
intermediate int4, which then undergoes nucleophilic attack of
aldehyde 2 to afford the desired product 3. It should be noted
that because of the lack of regio- and geometry-control, some
side products such as  adduct 9, (Z) isomer 10 and dimmer 11,
might also generate, but in our case, none of them was observed.
Actually, the coupling reaction of 1a with benzaldehyde 2a us-
ing other bases including t-BuOK, LDA, Hunig’s base,
1,2,2,6,6-pentamethylpiperidine and 2,2,6,6-tetramethylpiperi-
dine, didn’t work well and the expected (E)--adduct was ob-
tained in low (even zero) yields resulting from the mentioned
side products (see SI, Table S2).
Method A: Ethyl bromoacetate (30 mmol, 1.0 equiv) was
added dropwisely to a solution of Ph3P (30 mmol, 1.0 equiv) in
toluene (100 mL). After stirring at rt overnight, the resulting
white precipitate was filtered. The filter cake was dissolved in
water. The resulting solution was slowly basified with NaOH
solution (3 M) until pH 9, and then extracted with DCM (3 × 50
mL). The combined organic phase was washed successively
with water (2 × 30 mL) and brine (1 × 30 mL), and then dried
(MgSO4) and filtered. The filtrate was concentrated in vacuo to
give phosphorus salt, which was used in the next step without
further purification. The corresponding aldehyde (20 mmol, 1.0
equiv) in DCM (10 mL) was added slowly to a solution of phos-
phorus salt (24 mmol, 1.2 equiv) in DCM (40 mL) at 0 oC. The
resulting mixture was stirred at rt and monitored periodically by
TLC. After completion, the reaction mixture was concentrated
in vacuo, and then purified by flash column chromatography
[silica gel, EtOAc/PE = 1:20] to give the ,-unsaturated ester.
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Scheme 5 Another possible mechanism and some plausible
side products
Ethyl (E)-4-phenylbut-2-enoate (1a)39: Yield: 91% (3.44 g,
1
18.1 mmol). Colorless oil. H NMR (600 MHz, CDCl3) δ 7.30
(t, J = 7.8 Hz, 2H), 7.22 (t, J = 6.6 Hz, 1H), 7.16 (d, J = 7.8 Hz,
2H), 7.09 (dt, J = 15.6, 7.2 Hz, 1H), 5.80 (d, J = 15.6 Hz, 1H),
4.16 (q, J = 7.2 Hz, 2H), 3.50 (d, J = 7.2 Hz, 2H), 1.29 – 1.22
(m, 3H); 13C NMR (150 MHz, CDCl3) δ 166.3, 147.1, 137.6,
128.7, 128.6, 126.6, 122.3, 60.1, 38.2, 14.2.
Ethyl (E)-4-(4-tolyl)but-2-enoate (1b)40: Yield: 85% (3.47 g,
1
17.0 mmol). Colorless oil. H NMR (400 MHz, CDCl3) δ 7.07
In summary, we have developed a facile and efficient access
to -hydroxyl--vinyl carboxylic esters via DBU-catalyzed
coupling reaction of aldehydes with ,-unsaturated esters
bearing an activated  proton. Notable features of this approach
include readily available starting material, green and inexpen-
sive catalyst and solvent, mild conditions, convenient opera-
tions, good functional group compatibility, and excellent regio-
and geometry-specificity. The approach should therefore have
widespread applications in the synthesis of structurally diverse
-hydroxyl--vinyl carboxylic esters, which have been proved
to be versatile building blocks in the fast installation of many
important compounds, especially tetrahydrofuran, dihydrofuran
and furan derivatives.
– 6.93 (m, 5H), 5.71 (dt, J = 15.2, 1.6 Hz, 1H), 4.08 (q, J = 6.8
Hz, 2H), 3.38 (dd, J = 6.8, 1.2 Hz, 2H), 2.24 (s, 3H), 1.18 (t, J
= 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 166.4, 147.5,
136.1, 134.6, 129.3, 128.6, 122.1, 60.1, 38.0, 20.9, 14.2.
Ethyl (E)-4-(4-chlorophenyl)but-2-enoate (1c)41: Yield: 93%
(4.18 g, 18.6 mmol). Colorless oil. 1H NMR (400 MHz, CDCl3)
δ 7.30 (d, J = 8.4 Hz, 2H), 7.12 (d, J =8.4 Hz, 2H), 7.10-1.03
(m, 1H), 5.81 (d, J = 15.6 Hz, 1H), 4.20 (q, J = 6.8 Hz, 2H),
3.50 (d, J = 6.4 Hz, 2H), 1.29 (t, J = 6.8 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 166.2, 146.4, 136.1, 132.5, 130.1, 128.8,
122.7, 60.3, 37.7, 14.2.
Ethyl (E)-4-(4-nitrophenyl)but-2-enoate (1d)42: Yield: 83%
(3.91 g, 16.6 mmol). Pale soild. 1H NMR (600 MHz, CDCl3) δ
8.18 (d, J = 9.0Hz, 2H), 7.50 (d, J = 8.4 Hz, 2H), 6.57 (d, J =
16.2 Hz, 1H), 6.51 (dt, J = 16.2, 6.6 Hz, 1H), 4.20 (q, J = 7.2
◼
EXPERIMENTAL SECTION
Hz, 2H), 3.30 (d, J = 6.6 Hz, 2H), 1.30 (t, J = 7.2 Hz, 3H); 13
C
General Considerations. NMR spectra were recorded at rt
on Bruker Avance 400 MHz or 600 MHz spectrometers. The
NMR (100 MHz, CDCl3) δ 170.8, 146.9, 143.2, 131.4, 127.0,
126.7, 123.9, 61.0, 38.3, 14.1.
residual solvent signals were taken as the reference (0.00 ppm
1
for H NMR spectra and 77.0 ppm for 13C NMR spectra in
Ethyl (E)-4-(3-nitrophenyl)but-2-enoate (1e)42: Yield: 88%
(4.14 g, 17.6 mmol). Colorless oil. 1H NMR (600 MHz, CDCl3)
δ 8.12 (dt, J = 7.2, 1.8 Hz, 1H), 8.06 (s, 1H), 7.55 – 7.48 (m,
2H), 7.07 (dt, J = 15.6, 7.2 Hz, 1H), 5.84 (dt, J = 15.6, 1.2 Hz,
1H), 4.20 (q, J = 7.2 Hz, 2H), 3.64 (dd, J = 7.2, 1.2 Hz, 2H),
1.29 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 166.0,
145.0, 139.7, 135.0, 129.6, 123.7, 123.6, 121.9, 60.5, 37.9, 14.2.
CDCl3). Chemical shifts (δ) are reported in ppm, and coupling
constants (J) are given in Hz. HRMS (ESI) spectra were rec-
orded on a Waters Q-Tof premierTM mass spectrometer. All
solvents were distilled under nitrogen atmosphere from the fol-
lowing drying agents immediately before use: toluene and
DCM were distilled from CaH2; EtOH was distilled from Mg
powder; THF was distilled from Na. All reactions were carried
out in flame or oven-dried glassware with magnetic stirring un-
der argon atmosphere with freshly distilled dry solvents under
anhydrous conditions unless otherwise indicated. Reactions
were monitored by TLC on glass-backed plates coated with a
0.2 mm thickness of silica gel 60 F254; chromatograms were
visualized by fluorescence quenching with UV light at 254 nm
and then by staining with phosphomolybdic acid or sulfuric acid
Ethyl (E)-4-phenylpent-2-enoate (1h)39: Yield: 88% (3.60 g,
1
17.6 mmol). Colorless oil. H NMR (600 MHz, CDCl3) δ 7.32
(t, J = 7.2 Hz, 2H), 7.25 – 7.21 (m, 1H), 7.21 – 7.18 (m, 2H),
7.11 (dd, J = 15.6, 6.6 Hz, 1H), 5.80 (dd, J = 15.6, 1.2 Hz, 1H),
4.18 (q, J = 7.2 Hz, 2H), 3.61 (ddd, J = 13.8, 7.2, 1.2 Hz, 1H),
1.43 (d, J = 7.2 Hz, 3H), 1.27 (t, J = 7.2 Hz, 3H); 13C NMR (150
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MHz, CDCl3) δ 166.8, 152.6, 143.3, 128.7, 127.3, 126.7, 120.1,
60.3, 42.0, 20.3, 14.2.
Ethyl (E)-2-(hydroxy(phenyl)methyl)-4-phenylbut-3-enoate
(3aa):
(±)-syn-3aa: Yield: 32% (95.0 mg, 0.31 mmol). White solid.
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7
8
Methord B: KF (20.25 mmol) was added to a solution of
ethyl 4-bromocrotonate (6.8 mmol) in toluene/MeOH/H2O (34
mL, V/V/V 4:4:1) and the solution was stirred for 20 min at rt.
Then Pd(OAc)2 (0.1125 mmol) and -naphthalene boronic acid
(4.5 mmol) were added. The resulting mixture was exhausted
O2 for 5 min and kept stirring at reflux under Ar atmosphere
overnight. The reaction mixture was cooled to rt and EA (50
mL) were added. The organic layer was separated and washed
successively with H2O (2 × 15 mL), and brine (1 × 15 mL), then
dried (MgSO4) and filtered. The filtrate was concentrated in
vacuo and the resulting residue was purified by column chro-
matography [silica gel, EtOAc–PE = 1:20] to give the expected
product.
1H NMR (600 MHz, CDCl3) δ 7.37 – 7.34 (m, 4H), 7.33 – 7.28
(m, 4H), 7.26 (dt, J = 6.6, 1.8 Hz, 1H), 7.23 (dt, J = 7.8, 1.8 Hz,
1H), 6.46 (d, J = 15.6 Hz, 1H), 6.34 (dd, J = 15.6, 9.0 Hz, 1H),
5.02 (dd, J = 6.6, 3.0 Hz, 1H), 4.06 – 4.03 (m, 2H), 3.46 – 3.44
(t, J =9,6 Hz, 1H), 3.00 (d, J = 3 Hz, 1H), 1.11 (t, J = 7.2 Hz,
3H); 13C NMR (150 MHz, CDCl3) δ 172.5, 140.7, 136.5, 135.3,
128.5, 128.2, 127.9, 127.9, 126.5, 126.5, 123.1, 74.47, 61.0,
57.7, 14.0; ESI-HRMS calcd. for C19H20NaO3 ([M+Na]+)
319.1310, found 319.1312.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(±)-anti-3aa: Yield: 33% (97.7 mg, 0.34 mmol). White solid.
1H NMR (600 MHz, CDCl3) δ 7.41 – 7.18 (m, 10 H), 6.33 (d, J
= 16.2 Hz, 1H), 6.09 (dd, J = 15.6, 9.0 Hz, 1H), 5.02 (dd, J =
7.8, 5.4 Hz, 1H), 4.23 – 4.17 (m, 2H), 3.56 (t, J = 9.0 Hz, 1H),
3.03 (d, J = 5.4 Hz, 1H), 1.25 (t, J = 7.2 Hz, 3H); 13C NMR (150
MHz, CDCl3) δ 173.0, 141.2, 136.5, 134.2, 128.5, 128.4, 128.0,
127.8, 126.5, 126.4, 123.5, 75.6, 61.2, 57.2, 14.1; ESI-HRMS
calcd. for C19H20NaO3 ([M+Na]+) 319.1310, found 319.1310.
Ethyl (E)-4-(naphthalen-1-yl)but-2-enoate (1f): Yield: 73%
1
(790 mg, 3.29 mmol). Pale oil. H NMR (600 MHz, CDCl3) δ
7.92 (d, J = 8.4 Hz, 1H), 7.87 (d, J = 7.2 Hz, 1H), 7.77 (d, J =
7.8 Hz, 1H), 7.53 – 7.47 (m, 2H), 7.42 (t, J = 7.2 Hz, 1H), 7.32
(d, J = 7.2 Hz, 1H), 7.25 (dt, J = 15.6, 6.6 Hz, 1H), 5.76 (dt, J
= 15.6, 1.2 Hz, 1H), 4.14 (q, J = 7.2 Hz, 2H), 3.97 (dd, J = 7.2,
1.2 Hz, 2H), 1.24 (t, J = 7.2 Hz, 3H)；13C NMR (150 MHz,
CDCl3) δ 166.5, 146.9, 133.9, 133.9, 131.8, 128.8, 127.6, 126.9,
126.2, 125.7, 125.6, 123.7, 122.7, 60.3, 35.6, 14.2; ESI-HRMS
calcd for C16H16NaO2 ([M+Na]+) 263.1048, found 263.1053.
Ethyl (E)-2-((2-fluorophenyl)(hydroxy)methyl)-4-phenylbut-
3-enoate (3ab):
(±)-syn-3ab: Yield: 42% (132.0 mg, 0.42 mmol). White solid.
1H NMR (600 MHz, CDCl3) δ 7.47 (dt, J = 7.8, 1.2 Hz, 1H),
7.32 – 7.25 (m, 4H), 7.22 (m, 2H), 7.12 – 7.06 (m, 1H), 7.04 –
6.99 (m, 1H), 6.36 (d, J = 16.2 Hz, 1H), 6.30 (dd, J = 16.2, 9.0
Hz, 1H), 5.45 (t, J = 3.6 Hz, 1H), 4.18 – 4.11 (m, 2H), 3.57 (dd,
J = 9.0, 4.8 Hz, 1H), 3.38 (d, J = 3.6 Hz, 1H), 1.20 (t, J = 7.2
Methord C: Pd(PPh3)4 (0.2 mmol) was added to a solution
of ethyl 4-bromocrotonate (4 mmol) in dioxane (36 mL) under
argon atmosphere and the solution was stirred at rt for 10 min,
and then boronic acid (8 mmol) and Na2CO3 (20 mmol) were
added. The resulting reaction mixture was stirred at reflux. Af-
ter about 1 h, the mixture was cooled to rt, and EA (50 mL) were
added. The organic layer was separated and washed succes-
sively with H2O (2 × 15 mL), and brine (1 × 15 mL), then dried
(MgSO4) and filtered. The filtrate was concentrated in vacuo
and the resulting residue was purified by column chromatog-
raphy [silica gel, EtOAc–PE = 1:20] to give the expected prod-
uct.
Ethyl (E)-4-(thiophen-2-yl)but-2-enoate (1g)43: Yield: 78%
(612 mg, 3.12 mmol). Yellow oil. 1H NMR (600 MHz, CDCl3)
δ 7.18 (dd, J = 5.4, 1.2 Hz, 1H), 7.08 (dt, J = 15.6, 0.6 Hz, 1H),
6.95 (dd, J = 5.4, 1.2 Hz, 1H), 6.86 – 6.81 (m, 1H), 5.88 (dt, J
= 15.6, 1.8 Hz, 1H), 4.19 (q, J = 7.2 Hz, 2H), 3.71 (d, J = 7.2
Hz, 2H), 1.28 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3)
δ 166.3, 145.9, 139.8, 127.1, 125.6, 124.3, 122.6, 60.3, 32.3,
14.2.
Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 173.0, 159.5 (d, JC-F
=
244.5 Hz ), 136.5, 135.5, 129.2 (d, JC-F = 7.5 Hz ), 128.5, 128.4
(d, JC-F = 4.5 Hz), 127.7, 127.7 (d, JC-F = 10.5 Hz), 126.4, 124.0
(d, JC-F = 4.5 Hz), 122.2, 115.0 (d, JC-F = 22.5 Hz), 68.5 (d, JC-F
= 1.5 Hz), 61.2, 55.1, 14.0; ESI-HRMS calcd. for C19H19FNaO3
([M+Na]+) 337.1216, found 337.1217.
(±)-anti-3ab: Yield: 43% (135.3 mg, 0.43 mmol). White
solid. 1H NMR (600 MHz, CDCl3) δ 7.46 (dt, J = 7.8, 1.8 Hz,
1H), 7.26 – 7.19 (m, 6H), 7.14 (dt, J = 7.2, 6.0 Hz, 1H), 6.98
(m, 1H), 6.37 (d, J = 16.2 Hz, 1H), 6.18 (dd, J = 16.2, 9.6 Hz,
1H), 5.35 ( t, J = 7.2 Hz, 1H), 4.22 – 4.14 (m, 2H), 3.61 (t, J =
8.4 Hz, 1H), 3.25 (dd, J = 6.0, 1.8 Hz, 1H), 1.22 (t, J = 7.2 Hz,
3H); 13C NMR (150 MHz, CDCl3) δ 172.9, 159.9 (d, JC-F
=
243.0 Hz), 136.5, 134.5, 129.4 (d, JC-F = 7.5 Hz), 128.5, 128.4
(d, JC-F = 13.5 Hz), 127.8, 127.8 (d, JC-F = 4.5 Hz), 126.4, 124.3
(d, JC-F = 4.5 Hz), 123.2, 115.3 (d, JC-F = 21.0 Hz), 69.7, 61.2,
56.6, 14.1; ESI-HRMS calcd. for C19H19FNaO3 ([M+Na]+)
337.1216, found 337.1215.
Preparation for -hydroxyl--vinyl carboxylic esters
Ethyl (E)-2-((4-fluorophenyl)(hydroxy)methyl)-4-phenylbut-
3-enoate (3ac):
Method A: ,-Unsaturated ester 1 (1 mmol), DBU (20
mol%), aromatic/hetero aromatic/polycyclic aromatic aldehyde
2 (1 mmol) and EtOH (2 mL) were added successively to a
round-bottom flask. The resulting reaction mixture was stirred
at 0 oC for 12 h and then concentrated in vacuo. The residue was
purified by column chromatography [silica gel, EtOAc/PE 1:8
to 1:3] to give the expected product 3.
(±)-syn-3ac: Yield: 27% (85.0 mg, 0.27 mmol). White solid.
1H NMR (600 MHz, CDCl3) δ 7.36-7.30 (m, 6H), 7.27 – 7.24
(m, 1H), 7.01 (t, J = 8.4 Hz, 2H), 6.46 (d, J = 15.6 Hz, 1H),
6.31 (dd, J = 15.6, 9.6 Hz, 1H), 5.06 (dd, J = 6.0, 1.8 Hz, 1H),
4.12 – 4.04 (m, 2H), 3.41 (dd, J = 9.0, 6.0 Hz, 1H), 3.02 (t, J =
2.4 Hz,1H), 1.15 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz,
CDCl3) δ 172.5, 162.4 (d, JC-F = 244.5 Hz), 136.4 (d, JC-F = 1.5
Hz), 136.3, 135.7, 128.6, 128.2 (d, JC-F = 9.0 Hz), 128.0, 126.5,
122.7, 115.1 (d, JC-F = 21.0 Hz), 73.8, 61.1, 57.8, 14.0; ESI-
HRMS calcd. for C19H19FNaO3 ([M+Na]+) 337.1216, found
337.1206.
Method B: ,-Unsaturated ester 1 (1 mmol), DBU (20
mol%), aliphatic aldehyde 2 (1 mmol), THF (2 mL) and H2O
(27 uL) were added successively to a round-bottom flask. The
resulting reaction mixture was stirred at 0 oC for 12 h and then
concentrated in vacuo. The residue was purified by column
chromatography [silica gel, EtOAc/PE 1:8 to 1:3] to give the
expected product 3.
(±)-anti-3ac: Yield: 23% (72.3 mg, 0.23 mmol). Pale yellow
oil. 1H NMR (600 MHz, CDCl3) δ 7.32 – 7.28 (m, 2H), 7.27 –
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The Journal of Organic Chemistry
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+
7.20 (m, 5H), 7.02 – 6.97 (m, 2H), 6.31 (d, J = 15.6 Hz, 1H),
6.04 (dd, J = 15.6, 9.0 Hz, 1H), 4.99 (dd, J = 8.4, 5.4 Hz, 1H),
4.23 – 4.14 (m, 2H), 3.50 (t, J = 8.4 Hz, 1H), 3.16 (d, J = 5.4
Hz, 1H), 1.25 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3)
δ 173.0, 162.4 (d, JC-F = 367.5 Hz), 137.0 (d, JC-F = 6.0 Hz),
136.4, 134.5, 128.5, 128.2 (d, JC-F = 13.5 Hz), 127.9, 126.3,
123.2, 115.2 (d, JC-F = 31.5 Hz), 74.9, 61.2, 57.3, 14.1; ESI-
HRMS calcd. for C19H19FNaO3 ([M+Na]+) 337.1216, found
337.1210.
calcd. for C19H19ClNaO3 ([M+Na]+) 353.0920, found:
353.0918.
1
2
3
4
5
6
7
8
(±)-anti-3af: Yield: 23% (75.7 mg, 0.23 mmol). Pale yellow
oil. 1H NMR (600 MHz, CDCl3) δ 7.33 – 7.20 (m, 9H), 6.34 (d,
J = 15.6 Hz, 1H), 6.06 (dd, J = 15.6, 9.0 Hz, 1H), 4.99 (dd, J =
8.4, 5.4 Hz, 1H), 4.24 – 4.15 (m, 2H), 3.50 (t, J = 8.4 Hz, 1H),
3.14 (t, J = 5.4 Hz, 1H), 1.26 (t, J = 7.2 Hz, 3H); 13C NMR (150
MHz, CDCl3) δ 172.9, 139.7, 136.3, 134.6, 133.7, 128.5, 128.5,
127.9, 127.9, 126.4, 123.1, 74.8, 61.3, 57.1, 14.1; ESI-HRMS
+
Ethyl (E)-2-((2-chlorophenyl)(hydroxy)methyl)-4-phenylbut-
calcd. for C19H19ClNaO3 ([M+Na]+)
353.0920, found
9
3-enoate (3ad):
353.0911.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(±)-syn-3ad: Yield: 39% (129.2 mg, 0.39 mmol). White solid.
1H NMR (600 MHz, CDCl3) δ 7.52 (dd, J = 7.8, 1.8 Hz, 1H),
7.33 (dd, J = 7.8, 1.2 Hz, 1H), 7.27 (d, J = 4.2 Hz, 4H), 7.22 –
7.15 (m, 3H), 6.30 (dd, J = 16.2, 9.0 Hz, 1H), 6.21 (d, J = 16.2
Hz, 1H), 5.60 (t, J = 2.4 Hz, 1H), 4.25 – 4.17 (m, 2H), 3.64 (dd,
J = 9.0, 2.4 Hz, 1H), 3.57 (d, J = 2.4 Hz, 1H), 1.25 (t, J = 7.2
Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 173.7, 137.8, 136.6,
135.5, 131.4, 129.2, 128.7, 128.7, 128.5, 127.7, 126.7, 126.4,
121.7, 70.7, 61.4, 53.3, 14.1; ESI-HRMS calcd. for
C19H19ClNaO3+ ([M+Na]+) 353.0920, found 353.0919.
Ethyl (E)-2-((2-bromophenyl)(hydroxy)methyl)-4-phenyl-
but-3-enoate (3ag):
(±)-syn-3ag: Yield: 36% (134.7 mg, 0.36 mmol). Pale solid.
1H NMR (600 MHz, CDCl3) δ 7.51 (dd, J = 7.8, 1.2 Hz, 1H),
7.47 (dd, J = 7.8, 6.0 Hz, 1H), 7.29 ( m, 5H), 7.21 ( m,1H), 7.10
(dt, J = 7.8, 1.2 Hz, 1H), 6.38 (d, J = 16.2 Hz, 1H), 6.30 (dd, J
= 15.6, 9.0 Hz, 1H), 5.43 (t, J = 6.6 Hz, 1H), 4.17 – 4.12 (m,
2H), 3.69 (d, J = 6.6 Hz, 1H), 3.65 (dd, J = 8.4, 6.6 Hz, 1H),
1.19 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 173.7,
139.3, 136.6, 135.6, 132.5, 129.1, 129.0, 128.5, 127.7, 127.2,
126.4, 121.5, 121.5, 72.8, 61.4, 53.2, 14.1; ESI-HRMS calcd.
for C19H19BrNaO3 ([M+Na]+) 397.0415, found 397.0412.
(±) -anti-3ad: Yield: 41% (135.6 mg, 0.41 mmol). White
solid. 1H NMR (600 MHz, CDCl3) δ 7.52 (d, J = 7.2 Hz, 1H),
7.30 – 7.25 (m, 6H), 7.22 – 7.15 (m, 2H), 6.38 (d, J = 16.2 Hz,
1H), 6.27 (dd, J = 16.2, 9.0 Hz, 1H), 5.47 (t, J = 6.0 Hz, 1H),
4.17 – 4.11 (m, 2H), 3.64 ( dd, J = 9.0, 7.2 Hz, 1H) 3.62 (d, J =
6.6 Hz, 1H), 1.19 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz,
CDCl3) δ 173.0, 138.9, 136.5, 134.1, 132.3, 129.4, 128.9, 128.5,
127.7 (2C), 127.0, 126.4, 123.4, 72.0, 61.2, 56.1, 14.0; ESI-
HRMS calcd. for C19H19ClNaO3+ ([M+Na]+) 353.0920, found
353.0915.
(±)-anti-3ag: Yield: 37% (138.8 mg, 0.37 mmol). Pale yel-
low solid. 1H NMR (600 MHz, CDCl3) δ 7.51 (dd, J = 7.8, 1.2
Hz, 1H), 7.47 (dd, J = 7.8, 6.0 Hz, 1H), 7.29 ( m, 5H), 7.21
( m,1H), 7.10 (dt, J = 7.8, 1.2 Hz, 1H), 6.38 (d, J = 16.2 Hz,
1H), 6.30 (dd, J = 15.6, 9.0 Hz, 1H), 5.43 (t, J = 6.6 Hz, 1H),
4.17 – 4.12 (m, 2H), 3.69 (d, J = 6.6 Hz, 1H), 3.65 (dd, J = 8.4,
6.6 Hz, 1H), 1.19 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz,
CDCl3) δ 172.9, 140.5, 136.5, 134.2, 132.7, 129.2, 128.5, 128.0,
127.8, 127.6, 126.5, 123.4, 122.6, 74.2, 61.2, 56.0, 14.1; ESI-
HRMS calcd. for C19H19BrNaO3 ([M+Na]+) 397.0415, found
397.0410.
Ethyl (E)-2-((3-chlorophenyl)(hydroxy)methyl)-4-phenylbut-
3-enoate (3ae):
(±)-syn-3ae: Yield: 35% (115.6 mg, 0.35 mmol). White solid.
1H NMR (600 MHz, CDCl3) δ 7.39 – 7.19 (m, 9H), 6.45 (d, J =
16.2 Hz, 1H), 6.28 (dd, J = 16.2, 9.0 Hz, 1H), 5.04 (d, J = 6.0
Hz, 1H), 4.13 – 4.04 (m, 2H), 3.45 – 3.37 (m, 1H), 3.16 (s, 1H),
1.14 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 172.4,
142.8, 136.3, 135.7, 134.1, 129.5, 128.5, 128.0, 128.0, 126.7,
126.5, 124.6, 122.4, 73.7, 61.2, 57.5, 14.0; ESI-HRMS calcd.
for C19H19ClNaO3+ ([M+Na]+) 353.0920, found 353.0922.
Ethyl (E)-2-((4-bromophenyl)(hydroxy)methyl)-4-phenyl-
but-3-enoate (3ah):
(±)-syn-3ah: Yield: 24% (90.0 mg, 0.24 mmol). White solid.
1H NMR (600 MHz, CDCl3) δ 7.45 (d, J = 8.4 Hz, 2H), 7.35 (d,
J = 7.2 Hz, 2H), 7.31 (t, J = 7.2 Hz, 2H), 7.24 ( m, 3H), 6.44 (d,
J = 15.6 Hz, 1H), 6.29 (dd, J = 15.6, 9.0 Hz, 1H), 5.05 (dd, J =
5.4, 2.4 Hz, 1H), 4.13 – 4.05 ( m, 2H), 3.40 (dd, J = 9.0, 5.4 Hz,
(±)-anti-3ae: Yield: 36% (119.0 mg, 0.36 mmol). White solid.
1H NMR (600 MHz, CDCl3) δ 7.38 (s, 1H), 7.29 – 7.25 (m, 5H),
7.24 (d, J = 4.8 Hz, 2H), 7.19 (d, J = 3.0 Hz, 1H), 6.37 (d, J =
15.6 Hz, 1H), 6.09 (dd, J = 15.6, 9.0 Hz, 1H), 5.02 – 4.96 (m,
1H), 4.23 – 4.16 (m, 2H), 3.52 (t, J = 8.4 Hz, 1H), 3.23 (t, J =
4.2 Hz, 1H), 1.24 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz,
CDCl3) δ 172.8, 143.3, 136.3, 134.7, 134.4, 129.6, 128.5, 128.1,
127.9, 126.6, 126.4, 124.8, 123.1, 74.9, 61.3, 56.9, 14.1; ESI-
1H), 3.11 (dd, J = 5.4, 2.4 Hz, 1H), 1.17 (t, J = 7.2 Hz, 3H); 13
C
NMR (150 MHz, CDCl3) δ 172.6, 139.7, 136.3, 135.7, 131.4,
128.6, 128.2, 128.0, 126.5, 122.4, 121.7, 73.7, 61.2, 57.4, 14.0;
ESI-HRMS calcd. for C19H19BrNaO3 ([M+Na]+) 397.0415,
found 397.0410.
(±)-anti-3ah: Yield: 24% (89.6 mg, 0.24 mmol). White solid.
1H NMR (600 MHz, CDCl3) δ 7.45 (d, J = 8.4 Hz, 2H), 7.30 –
7.21 (m, 7H), 6.35 (d, J = 16.2 Hz, 1H), 6.07 (dd, J = 16.2, 9.0
Hz, 1H), 4.98 (dd, J = 7.8, 5.4 Hz, 1H), 4.24-4.16 (m, 2H), 3.50
(t, J = 7.8 Hz, 1H), 3.11 (d, J = 5.4 Hz, 1H), 1.25 (t, J = 7.2 Hz,
3H); 13C NMR (150 MHz, CDCl3) δ 172.9, 140.3, 136.3, 134.6,
131.5, 128.6, 128.2, 127.9, 126.4, 123.0, 121.8, 74.9, 61.3, 57.0,
14.1; ESI-HRMS calcd. for C19H19BrNaO3 ([M+Na]+)
397.0415, found 397.0414.
+
HRMS
calcd.
for
C19H19ClNaO3
([M+Na]+)
C19H19ClNaO3(M+Na)+ 353.0920, found: 353.0913.
Ethyl (E)-2-((4-chlorophenyl)(hydroxy)methyl)-4-phenyl-
but-3-enoate (3af):
(±)-syn-3af: Yield: 26% (86.3 mg, 0.26 mmol). White solid.
1H NMR (600 MHz, CDCl3) δ 7.36 – 7.22 (m, 9H), 6.44 (d, J =
16.2 Hz, 1H), 6.29 (dd, J = 16.2, 9.0 Hz, 1H), 5.06 (dd, J = 6.0,
2.4 Hz, 1H), 4.12 – 4.06 (m, 2H), 3.40 (dd, J = 9.6, 6.0 Hz, 1H),
3.11 (d, J = 2.4 Hz, 1H), 1.16 (t, J = 7.2 Hz, 3H); 13C NMR (150
MHz, CDCl3) δ 172.5, 139.2, 136.3, 135.7, 133.6, 128.6, 128.4,
128.0, 127.9, 126.5, 122.4, 73.7, 61.2, 57.5, 14.0; ESI-HRMS
Ethyl (E)-2-(hydroxy(2-nitrophenyl)methyl)-4-phenylbut-3-
enoate (3ai):
(±)-syn-3ai: Yield: 30% (102.4 mg, 0.30 mmol). Pale yellow
solid. 1H NMR (600 MHz, CDCl3) δ 7.97 (dd, J = 7.8, 1.2 Hz,
1H), 7.78 (d, J = 7.8 Hz, 1H), 7.58 – 7.54 (m, 1H), 7.42 – 7.38
(m, 1H), 7.28-7.18 (m, 5H), 6.34 (dd, J = 15.6, 9.0 Hz, 1H),
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The Journal of Organic Chemistry
6.24 (d, J = 15.6 Hz, 1H), 5.81 (d, J = 3.0 Hz, 1H), 4.24-4.14 Ethyl (E)-2-(hydroxy(2-methoxyphenyl)methyl)-4-phenylbut-
1
2
3
4
5
6
7
8
(m, 2H), 3.85 (s, 1H), 3.71 (dd, J = 9.0, 3.0 Hz, 1H), 1.26 (t, J
= 7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 173.7, 147.5,
136.1, 136.1, 133.1, 129.7, 128.8, 128.6, 128.4, 127.9, 126.4,
124.5, 121.4, 69.5, 61.6, 54.4, 14.1; ESI-HRMS calcd. for
C19H19NNaO5 ([M+Na]+) 364.1161, found 364.1161.
3-enoate (3al):
(±)-syn-3al: Yield: 33% (107.9 mg, 0.33 mmol). White solid.
1H NMR (600 MHz, CDCl3) δ 7.35 – 7.30 (m, 3H), 7.27 (t, J =
7.2 Hz, 2H), 7.21 (dd, J = 9.6, 7.2 Hz, 2H), 6.91 (t, J = 7.2 Hz,
1H), 6.87 (d, J = 8.4 Hz, 1H), 6.38 – 6.31 (m, 2H), 5.32 (s, 1H),
4.09 (q, J = 7.2 Hz, 2H), 3.85 (s, 3H), 3.68 (s, 1H), 3.51 (s, 1H),
1.17 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 173.2,
156.2, 136.8, 134.4, 128.6, 128.4, 128.1, 127.5, 126.3, 123.6,
120.5, 110.3, 71.2, 60.8, 55.3, 54.8, 14.0; ESI-HRMS calcd. for
C20H22NaO4 ([M+Na]+) 349.1416, found 349.1416.
(±)-anti-3ai: Yield: 33% (112.3 mg, 0.33 mmol). Pale yellow
solid. 1H NMR (600 MHz, CDCl3) δ 7.90 (dd, J = 8.4, 1.2 Hz,
1H), 7.77 (dd, J = 7.8, 1.2 Hz, 1H), 7.66 – 7.61 (m, 1H), 7.44 –
7.40 (m, 1H), 7.30- 7.27 (m, 4H), 7.23-7.20 (m, 1H), 6.41 (d, J
=15.6 Hz, 1H), 6.25 (dd, J = 15.6, 9.0 Hz, 1H), 5.72 (t, J = 6.6
Hz, 1H), 4.14 (q, J = 7.2 Hz, 2H), 3.92 (d, J = 6.6 Hz, 1H), 3.67
(dd, J = 9.0, 6.6 Hz, 1H), 1.19 (t, J = 7.2 Hz, 3H); 13C NMR
(150 MHz, CDCl3) δ 172.8, 148.1, 136.9, 136.2, 134.7, 133.4,
128.6, 128.6, 128.5, 127.9, 126.5, 124.6, 123.0, 70.8, 61.4, 56.1,
14.0; ESI-HRMS calcd. for C19H19NNaO5 ([M+Na]+) 364.1161,
found 364.1158.
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(±)-anti-3al: Yield: 31% (101.2 mg, 0.31 mmol). White solid.
1H NMR (600 MHz, CDCl3) δ 7.28 (dd, J = 7.2, 1.2 Hz, 1H),
7.26 - 7.25 (s, 2H), 7.24 (s, 2H), 7.24 -7.22 (m, 1H), 7.22 -7.18
(m, 1H), 6.92 (dt, J = 7.2, 1.2 Hz, 1H), 6.85 (d, J = 7.2 Hz, 1H),
6.30 (d, J = 15.6 Hz, 1H), 6.17 (dd, J = 15.6, 9.0 Hz, 1H), 5.21
(t, J = 7.8 Hz, 1H), 4.18 (dq, J = 7.2, 1.2 Hz, 2H), 3.85 (s, 3H),
3.72 (t, J = 7.8 Hz, 1H), 3.52 (d, J = 9.0 Hz, 1H), 1.24 (t, J =
7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 173.1, 156.6, 136.8,
133.4, 128.9, 128.4, 127.9, 127.6, 126.3, 124.4, 120.7, 110.5,
72.7, 61.0, 56.2, 55.3, 14.2; ESI-HRMS calcd. for C20H22NaO4
([M+Na]+) 349.1416, found 349.1409.
Ethyl (E)-2-(hydroxy(4-nitrophenyl)methyl)-4-phenylbut-3-
enoate (3aj):
(±)-syn-3aj: Yield: 30% (102.1 mg, 0.30 mmol). Pale yellow
solid. 1H NMR (600 MHz, CDCl3) δ 8.19 (d, J = 9.0 Hz, 2H),
7.53 (d, J = 8.4 Hz, 2H), 7.31 – 7.22 (m, 5H), 6.36 (d, J = 16.2
Hz, 1H), 6.10 (dd, J = 16.2, 9.0 Hz, 1H), 5.13 (dd, J = 7.2, 6.0
Hz, 1H), 4.23 – 4.17 (m, 2H), 3.52 (t, J = 9.0 Hz, 1H), 3.40 (d,
J = 6.0 Hz, 1H), 1.25 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz,
CDCl3) δ 172.6, 148.5, 147.6, 136.0, 135.3, 128.6, 128.2, 127.4,
126.4, 123.5, 122.4, 74.6, 61.6, 56.9, 14.1; ESI-HRMS calcd.
for C19H19NNaO5 ([M+Na]+) 364.1161, found 364.1163.
Ethyl (E)-2-(hydroxy(4-methoxyphenyl)methyl)-4-phenylbut-
3-enoate (3am):
(±)-syn-3am: Yield: 17% (55.5 mg, 0.17 mmol). White solid.
1H NMR (600 MHz, CDCl3) δ 7.37 (d, J = 7.8 Hz, 2H), 7.31 (m,
4H), 7.26 (d, J = 1.2 Hz, 1H), 6.86 (d, J = 7.2 Hz, 2H), 6.49 (d,
J = 16.2 Hz, 1H), 6.34 (dd, J = 16.2, 7.8 Hz, 1H), 5.02 (d, J =
7.2 Hz, 1H), 4.05-4.08 (m, 2H), 3.79 (s, 3H), 3.44 (t, J = 7.2 Hz,
1H), 2.87 (s, 1H), 1.13 (t, J = 7.2 Hz, 3H); 13C NMR (151 MHz,
CDCl3) δ 172.5, 159.3, 136.5, 135.3, 132.9, 128.6, 127.9, 127.8,
126.5, 123.3, 113.7, 74.1, 61.0, 57.9, 55.3, 14.0; ESI-HRMS
calcd. for C20H22NaO4 ([M+Na]+) 349.1416, found 349.1412.
(±)-anti-3aj: Yield: 32% (108.7 mg, 0.32 mmol). Pale yellow
solid. 1H NMR (600 MHz, CDCl3) δ 8.19 (d, J = 9.0 Hz, 2H),
7.53 (d, J = 8.4 Hz, 2H), 7.31 – 7.22 (m, 5H), 6.36 (d, J = 16.2
Hz, 1H), 6.10 (dd, J = 16.2, 9.0 Hz, 1H), 5.13 (dd, J = 7.2, 5.4
Hz, 1H), 4.23 – 4.17 (m, 2H), 3.52 (t, J = 7.2 Hz, 1H), 3.40 (d,
J = 5.4 Hz, 1H), 1.25 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz,
CDCl3) δ 172.6, 148.5, 147.6, 136.0, 135.3, 128.6, 128.2, 127.4,
126.4, 123.5, 122.4, 74.6, 61.5, 56.9, 14.1; ESI-HRMS calcd.
for C19H19NNaO5 ([M+Na]+) 364.1161, found 364.1168.
(±)-anti-3am: Yield: 15% (48.4 mg, 0.15 mmol); Colorless
oil. 1H NMR (600 MHz, CDCl3) δ 7.27-7.21 (m, 7H), 6.85 (d,
J = 9.0 Hz, 2H), 6.34 (d, J = 15.6 Hz, 1H), 6.05 (dd, J = 15.6,
9.0 Hz, 1H), 4.98 (d, J = 8.4 Hz, 1H), 4.25-4.17 (m, 2H), 3.78
(s, 3H), 3.75 (s, 1H), 3.54 (t, J = 9.0 Hz, 1H), 1.27 (t, J = 7.2
Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 173.1, 159.3, 136.6,
134.1, 133.4, 128.5, 127.7, 127.7, 126.4, 123.6, 113.8, 75.2,
61.1, 57.2, 55.2, 14.1; ESI-HRMS calcd. for C20H22NaO4
([M+Na]+) 349.1416, found 349.1424.
Ethyl (E)-2-(hydroxy(3-nitrophenyl)methyl)-4-phenylbut-3-
enoate (3ak):
(±)-syn-3ak: Yield: 26% (88.8 mg, 0.26 mmol). White solid.
1H NMR (600 MHz, CDCl3) δ 8.26 (s, 1H), 8.12 (dd, J = 7.8,
1.2 Hz, 1H), 7.71 (d, J = 7.2 Hz, 1H), 7.49 (t, J = 7.8 Hz, 1H),
7.34 – 7.28 (m, 4H), 7.24 (m, 1H), 6.43 (d, J = 16.2 Hz, 1H),
6.28 (dd, J = 16.2, 9.0 Hz, 1H), 5.23 (dd, J = 5.4, 3.0 Hz, 1H),
4.18 – 4.09 (m, 2H), 3.45 (dd, J = 9.0, 5.4 Hz, 1H), 3.42 (d, J =
3.0 Hz, 1H), 1.19 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz,
CDCl3) δ 172.5, 148.2, 142.9, 136.4, 136.0, 132.6, 129.2, 128.6,
128.2, 126.5, 122.8, 121.5, 121.4, 73.2, 61.5, 57.1, 14.0; ESI-
HRMS calcd. for C19H19NNaO5 ([M+Na]+) 364.1161, found
364.1162.
Ethyl (E)-2-(hydroxy(quinolin-2-yl)methyl)-4-phenylbut-3-
enoate (3an): Yield: 78% (271.0 mg, 0.78 mmol, dr = 1:1). 1H
NMR (600 MHz, CDCl3) δ 8.14 (d, J = 8.4 Hz, 1H), 8.09 (d, J
= 8.4 Hz, 1H), 8.05 (dd, J = 15.0, 8.4 Hz, 2H), 7.80 (dd, J =
7.8, 4.2 Hz, 2H), 7.74-7.69 (m, 2H), 7.56-7.51 (m, 2H), 7.47 (d,
J = 8.4 Hz, 1H), 7.35 (d, J = 8.4 Hz, 1H), 7.32-7.27 (m, 4H ),
7.24-7.21 (m, 5H), 7.19 – 7.15 (m, 1H), 6.38 (dd, J = 16.2 Hz,
1H), 6.36 (d, J = 15.0 Hz, 1H), 6.33 (dd, J = 15.6, 9.0 Hz, 1H),
6.28 (d, J = 16.2 Hz, 1H), 5.43 (d, J = 4.2 Hz, 1H), 5.23 (d, J =
6.6 Hz, 1H), 4.98 (s, 1H), 4.89 (s, 1H), 4.23 – 4.15 (m, 4H),
3.75 (dd, J = 9.6, 4.8 Hz, 1H), 3.67 (dd, J = 9.0, 7.2 Hz, 1H),
1.25 (t, J = 7.2 Hz, 3H), 1.21 (t, J = 7.2 Hz, 3H); 13C NMR (150
MHz, CDCl3) δ 172.5, 172.2, 159.4, 159.3, 146.8, 146.7, 136.8,
136.7, 136.5, 136.3, 134.6, 134.4, 129.8, 129.8, 128.9, 128.9,
128.5, 128.4, 127.8, 127.7, 127.6, 127.6, 127.6, 127.6, 126.6,
126.5, 126.4, 126.4, 123.6, 122.9, 119.7, 118.8, 74.8, 74.2, 61.2,
61.0, 57.5, 56.1, 14.2, 14.1; ESI-HRMS calcd. for
C22H21NNaO3 ([M+Na]+) 370.1419, found 370.1417.
(±)-anti-3ak: Yield: 22% (75.1 mg, 0.22 mmol). White solid.
1H NMR (600 MHz, CDCl3) δ 8.25 (t, J = 1.8 Hz, 1H), 8.09
(ddd, J = 8.4, 2.4, 1.2 Hz, 1H), 7.65 (d, J = 7.8 Hz, 1H), 7.46
(t, J = 7.8 Hz, 1H), 7.29 – 7.20 (m, 5H), 6.34 (d, J = 16.2 Hz,
1H), 6.09 (dd, J = 16.2, 9.0 Hz, 1H), 5.13 (dd, J = 8.4, 5.4 Hz,
1H), 4.24 – 4.15 (m, 2H), 3.54 (t, J = 8.4 Hz, 1H), 3.47 (t, J =
5.4 Hz, 1H), 1.23 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz,
CDCl3) δ 172.7, 148.2, 143.5, 136.0, 135.3, 132.7, 129.2, 128.6,
128.1, 126.4, 122.9, 122.4, 121.5, 74.5, 61.5, 57.0, 14.1; ESI-
HRMS calcd. for C19H19NNaO5 ([M+Na]+) 364.1161, found
364.1157.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Ethyl (E)-2-(hydroxy(thiophen-2-yl)methyl)-4-phenylbut-3-
Page 8 of 13
126.4, 124.2, 72.5, 61.0, 56.3, 36.9, 18.7, 14.2, 13.9; ESI-
HRMS calcd. for C16H22NaO3 ([M+Na]+) 285.1467, found
285.1458.
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8
enoate (3ao):
(±)-syn-3ao: Yield: 18% (54.3 mg, 0.18 mmol). White solid.
1H NMR (600 MHz, CDCl3) δ 7.38 (d, J = 7.8 Hz, 2H), 7.32 (t,
J = 7.8 Hz, 2H), 7.29 – 7.23 (m, 2H), 7.00 (d, J = 3.6 Hz, 1H),
6.95(dd, J = 4.8, 3.6 Hz, 1H), 6.57 (d, J = 15.6 Hz, 1H), 6.36
(dd, J = 15.6, 9.0 Hz, 1H), 5.36 (dd, J = 6.0, 3.0 Hz, 1H), 4.17
– 4.07 (m, 2H), 3.54 (dd, J = 9.0, 6.0 Hz, 1H), 3.15 (d, J = 3. 0
Hz, 1H), 1.19 (t, J = 7.2 Hz, 3H); 13C NMR (151 MHz, CDCl3)
δ 172.3, 144.3, 136.4, 135.8, 128.6, 128.0, 126.6, 126.4, 125.1,
124.7, 122.6, 70.8, 61.2, 57.8, 14.0; ESI-HRMS calcd. for
C17H18SNaO3 ([M+Na]+) 325.0874, found 325.0874.
Ethyl hydroxy-2-((E)-styryl)nonanoate (3ar):
(±)-syn-3ar: Yield: 35% (106.3 mg, 0.35 mmol). Colorless
oil. 1H NMR (600 MHz, CDCl3) δ 7.39 (d, J = 1.2 Hz, 2H), 7.30
(t, J = 1.2 Hz, 2H), 7.23 (m, 1H), 6.54 (d, J = 15.6 Hz, 1H), 6.34
(dd, J = 15.6, 9.6 Hz, 1H), 4.21 – 4.14 (m, 2H), 3.99 (dt, J = 8.4,
4.2 Hz, 1H), 3.19 (dd, J = 9.6, 4.2 Hz, 1H), 2.83 (s, 1H), 1.52 –
1.24 (m, 13H), 0.87 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz,
CDCl3) δ 173.4, 136.5, 134.9, 128.4, 127.7, 126.4, 123.1, 71.7,
60.9, 55.1, 34.2, 31.7, 29.1, 25.5, 22.5, 14.0, 13.9; ESI-HRMS
calcd. for C19H28NaO3 ([M+Na]+) 327.1936, found 327.1929.
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(±)-anti-3ao: Yield: 19% (57.3 mg, 0.19 mmol). White solid.
1H NMR (600 MHz, CDCl3) δ 7.31-7.27 (m, 4H), 7.25 – 7.21
(m, 2H), 6.98 (d, J = 9.0 Hz, 1H), 6.93 (dd, J = 4.8, 3.6 Hz, 1H),
6.47 (d, J = 15.9 Hz, 1H), 6.14 (dd, J = 15.9, 9.0 Hz, 1H), 5.27
(t, J = 6.0 Hz, 1H), 4.26-4.17 (m, 2H), 3.63 (t, J = 9.0 Hz, 1H),
3.25 (d, J = 6.0 Hz, 1H), 1.27 (t, J = 7.2 Hz, 3H); 13C NMR (150
MHz, CDCl3) δ 172.7, 145.2, 136.4, 134.7, 128.5, 127.9, 126.6,
126.4, 125.2, 124.7, 123.0, 71.6, 61.3, 57.2, 14.1; ESI-HRMS
calcd. for C17H18SNaO3 ([M+Na]+) 325.0874, found 325.0873.
(±)-anti-3ar: Yield: 37% (112.3 mg, 0.37 mmol). Colorless
oil. 1H NMR (400 MHz, CDCl3) δ 7.32 (d, J = 7.2 Hz, 2H), 7.24
(t, J = 7.2 Hz, 2H), 7.17 (t, J = 7.2 Hz, 1H), 6.48 (d, J = 15.6
Hz, 1H), 6.26 (dd, J = 15.6, 9.6 Hz, 1H), 4.12 (dq, J = 7.2, 2.4
Hz, 2H), 3.91 (dt, J = 8.4, 4.4 Hz, 1H), 3.12 (dd, J = 9.6, 4.4 Hz,
1H), 2.69 (s, 1H), 1.60 – 1.26 (m, 13H), 0.80 (t, J = 7.2 Hz, 3H);
13C NMR (150 MHz, CDCl3) δ 173.2, 136.5, 134.0, 128.5,
127.7, 126.4, 124.2, 72.7, 60.9, 56.3, 34.7, 31.7, 29.1, 25.4, 22.5,
14.1, 14.0; ESI-HRMS calcd. for C19H28NaO3 ([M+Na]+)
327.1936, found 327.1930.
Ethyl 3-hydroxy-2-((E)-styryl)pentanoate (3ap):
(±)-syn-3ap: Yield: 37% (92.1 mg, 0.37 mmol). Pale oil. 1H
NMR (600 MHz, CDCl3) δ 7.38 (d, J = 7.2 Hz, 2H), 7.31 (t, J
= 7.8 Hz, 2H), 7.27 – 7.22 (m, 1H), 6.55 (d, J = 15.6 Hz, 1H),
6.20 (dd, J = 15.6, 9.0 Hz, 1H), 4.25 – 4.15 (m, 2H), 3.86 (ddd,
J = 10.8, 7.8, 3.0Hz, 1H) 3.25 (t, J = 9.0 Hz, 1H), 2.55 (dd, J =
6.6, 4.2 Hz, 1H), 1.69-1.62 (m, 1H), 1.47-1.40 (m, 1H), 1.28 (t,
J = 7.2 Hz, 3H), 1.00 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz,
CDCl3) δ 173.3, 136.5, 134.0, 128.6, 127.8, 126.4, 124.2, 74.0,
61.0, 55.9, 27.6, 14.2, 9.8; ESI-HRMS calcd. for C15H20NaO3
([M+Na]+) 271.1310, found 271.1307.
(±)-anti-3ap: Yield: 41% (101.5 mg, 0.41 mmol). Pale oil. 1H
NMR (600 MHz, CDCl3) δ 7.40 (d, J = 7.2 Hz, 2H), 7.32 (t, J
= 7.2 Hz, 2H), 7.24 (d, J = 5.4 Hz, 1H), 6.56 (d, J = 16.2 Hz,
1H), 6.33 (dd, J = 16.2, 9.6 Hz, 1H), 4.23 – 4.15 (m, 2H), 3.92
(dt, J =7.8, 4.8 Hz, 1H), 3.22 (dd, J = 9.6, 4.2 Hz, 1H), 2.80 (d,
J = 3.0 Hz, 1H), 1.57 – 1.47 (m, 2H), 1.28 (t, J = 7.2 Hz, 3H),
0.98 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 173.6,
136.5, 135.1, 128.6, 127.8, 126.4, 123.0, 73.2, 61.1, 54.7, 27.1,
14.1, 10.0; ESI-HRMS calcd. for C15H20NaO3 ([M+Na]+)
271.1310, found 271.1309.
Ethyl
(3as):
3-hydroxy-5,9-dimethyl-2-((E)-styryl)dec-8-enoate
Less polar isomers: Yield: 33% (113.0 mg, 0.33 mmol). dr =
1:2; Colorless oil. H NMR (400 MHz, CDCl3) δ 7.43 (d, J =
1
7.6 Hz, 2H), 7.34 (t, J = 7.6 Hz, 2H), 7.27 (dt, J = 7.6, 2.0 Hz,
1H), 6.58 (d, J = 16.0 Hz, 1H), 6.36 (dd, J = 16.0, 1.2 Hz, 1H),
5.11 (tt, J = 9.6, 1.2 Hz, 1H), 4.22 (q, J = 7.2 Hz, 2H), 4.15 –
4.10 (m, 1H), 3.21 – 3.16 (m, 1H), 2.79 (br s, 0.33H), 2.68 (s,
0.67H), 2.10 – 1.93 (m, 2H), 1.72 – 1.67 (m, 3H), 1.66 – 1.56
(m, 4H), 1.47 – 1.36 (m, 2H), 1.31 (t, J = 7.2 Hz, 3H), 1.26 –
1.09 (m, 2H), 0.96 (d, J = 6.8 Hz, 1H), 0.94 (d, J = 6.8 Hz, 2H);
13C NMR (100 MHz, CDCl3) δ 173.5, 173.3, 136.6, 136.5,
135.1, 135.0, 131.2, 131.0, 128.5, 127.7, 126.4, 124.7, 124.7,
123.2, 122.9, 69.9, 69.6, 61.0, 60.9, 55.9, 55.1, 41.6, 41.6, 37.8,
36.4, 29.1, 28.7, 25.6, 25.4, 25.3, 20.2, 18.9, 17.5, 14.1; ESI-
HRMS calcd. for C22H32NaO3 ([M+Na]+) 367.2249, found
367.2256.
More polar isomers: Yield: 33% (113.7 mg, 0.33 mmol). dr
= 1:1.3. Colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.38 (d, J
= 7.2 Hz, 2H), 7.31 (t, J = 7.2 Hz, 2H), 7.26 – 7.22 (m, 1H),
6.55 (d, J = 15.6 Hz, 1H), 6.20 (ddd, J = 15.6, 9.2, 6.4 Hz, 1H),
5.10 – 5.07 (m, 1H), 4.24 – 4.15 (m, 2H), 4.02 (m, 1H), 3.20 (t,
J = 8.4 Hz, 1H), 2.47 (br s, 0.43H), 2.42 (br s, 0.56H), 2.00 –
1.93 (m, 2H), 1.79 – 1.67 (m, 2H), 1.67 (s, 3H), 1.58 (s, 3H),
1.49 – 1.42 (m, 1H), 1.37 – 1.73 [m, 5H, including 1.28 (t, J =
7.2 Hz, 3H)], 0.93 (d, J = 6.4 Hz, 1.3H), 0.90 (d, J = 6.4 Hz,
1.7H); 13C NMR (100 MHz, CDCl3) δ 173.2, 173.2, 136.6,
134.1, 134.1, 131.2, 131.1, 128.5, 127.8, 126.4, 124.7, 124.7,
124.3, 124.2, 71.1, 70.6, 60.9, 56.9, 56.6, 42.5, 42.1, 37.9, 36.0,
29.2, 28.8, 25.6, 25.5, 25.2, 20.4, 18.9, 17.6, 17.6, 14.1; ESI-
HRMS calcd. for C22H32NaO3 ([M+Na]+) 367.2249, found
367.2255.
Ethyl 3-hydroxy-2-((E)-styryl)hexanoate (3aq):
(±)-syn-3aq: Yield: 34% (89.2 mg, 0.34 mmol). Colorless oil.
1H NMR (600 MHz，CDCl3）δ 7.40 (d, J = 7.2 Hz, 2H), 7.31
(t, J = 7.2 Hz, 2H), 7.27-7.22 (m, 1H), 6.55 (d, J = 15.6 Hz,
1H), 6.3(dd, J = 15.6, 9.0 Hz, 1H), 4.23-4.15 (m, 2H), 4.01 (dt,
J = 7.8, 4.2 Hz, 1H), 3.19 (dd, J = 9.0, 4.2 Hz, 1H), 2.79 (s, 1H),
1.56-1.47 (m, 2H)，1.43-1.35 (m, 2H), 1.28 (t, J = 7.2 Hz, 3H),
0.92 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 173.5,
136.5, 135.0, 128.5, 127.8, 126.4, 123.0, 71.5, 61.0, 55.1, 36.3,
18.8, 14.1, 13.9; ESI-HRMS calcd. for C16H22NaO3 ([M+Na]+)
285.1467, found 285.1466.
(±)-anti-3aq: Yield: 39% (102.0 mg, 0.39 mmol). Colorless
oil. 1H NMR (600 MHz, CDCl3) δ 7.31 (d, J = 7.2 Hz, 2H), 7.24
(t, J = 7.2 Hz, 2H), 7.19 – 7.15 (m, 1H), 6.48 (d, J = 16.2 Hz,
1H), 6.13 (dd, J = 15.6, 9.0 Hz, 1H), 4.18 – 4.07 (m, 2H), 3.86
(dd, J = 13.8, 6.6 Hz, 1H), 3.16 (dd, J = 9.0, 1.8 Hz, 1H), 2.46
(d, J = 6.6 Hz, 1H), 1.53 – 1.43 (m, 2H), 1.38 – 1.27 (m, 2H),
1.23 – 1.17 (t, J = 7.2 Hz, 3H), 0.84 (t, J = 7.2 Hz, 3H); 13C
NMR (150 MHz, CDCl3) δ 173.3, 136.6, 134.1, 128.6, 127.8,
Ethyl 3-hydroxy-4-methyl-2-((E)-styryl)pentanoate (3at):
(±)-syn-3at: Yield: 25% (65.5 mg, 0.25 mmol). Colorless oil.
1H NMR (400 MHz, CDCl3) δ 7.41 (t, J = 7.6 Hz, 2H), 7.35 -
7.29 (m, 2H), 7.26 (t, J = 7.6 Hz, 1H), 6.59 (dd, J = 16.0, 8.4
Hz, 1H), 6.36 (dt, J = 16.0, 9.2 Hz, 1H), 4.22 – 4.17 (m, 2H),
3.72 - 3.69 (m, 1H), 3.38 (dd, J = 9.2, 4.4 Hz, 1H), 2.82 (s, 1H),
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The Journal of Organic Chemistry
MHz, CDCl3) δ 172.8, 159.8 (d, JC-F = 243.0 Hz), 135.0, 133.5,
1.73 (q, J = 6.8 Hz, 1H), 1.28 (dd, J = 14.4, 7.2 Hz, 3H), 1.05 -
1.00 (m, 3H), 0.95 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 173.7, 136.7, 134.8, 128.6, 127.8, 126.5, 123.2, 76.7,
61.0, 52.8, 31.0, 19.2, 17.8, 14.1; ESI-HRMS calcd. for
C16H22NaO3 ([M+Na]+) 285.1467, found 285.1471.
133.2, 129.5 (d, JC-F = 7.5 Hz), 128.7, 128.4 (d, JC-F = 13.5 Hz),
127.7 (d, JC-F = 3.0 Hz), 127.6, 124.3 (d, JC-F = 1.5 Hz), 123.9,
115.2 (d, JC-F = 21.0 Hz), 69.7, 61.3, 56.6, 14.1; ESI-HRMS
calcd. for C19H18ClFNaO3([M+Na]+) 371.0826, found 371.0822.
1
2
3
4
(±)-anti-3at: Yield: 20% (52.4 mg, 0.20 mmol). Colorless oil.
1H NMR (400 MHz, CDCl3) δ 7.37 (d, J = 7.2 Hz, 2H), 7.31 (t,
J = 7.2 Hz, 2H), 7.27 – 7.20 (t, J = 7.2 Hz, 1H), 6.56 (d, J = 16.0
Hz, 1H), 6.19 (dd, J = 16.0, 9.2 Hz, 1H), 4.21 – 4.16 (m, 2H),
3.75 (s, 1H), 3.37 (t, J = 8.4 Hz, 1H),2.54 (s, 1H), 1.81 – 1.76
(m, 1H), 1.30 – 1.25 (m, 3H), 1.00 (d, J = 6.8 Hz, 3H), 0.93 (d,
J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 173.6, 136.6,
133.7, 128.6, 127.8, 126.4, 124.5, 77.2, 61.0, 53.8, 30.7, 19.9,
15.4, 14.2; ESI-HRMS calcd. for C16H22NaO3 ([M+Na]+)
285.1467, found 285.1473.
Ethyl (E)-2-((2-fluorophenyl)(hydroxy)methyl)-4-(4-nitro-
phenyl)but-3-enoate (3db):
5
6
7
8
(±)-syn-3db: Yield: 33% (118.5 mg, 0.33 mmol). Pale yellow
solid. 1H NMR (600 MHz, CDCl3) δ 8.13 (d, J = 8.4 Hz, 2H),
7.47 – 7.43 (m, 1H), 7.41 (d, J = 9.0 Hz, 2H), 7.25 (m, 1H), 7.10
(t, J = 7.2 Hz, 1H), 7.04 (m, 1H), 6.50 (dd, J = 15.6, 9.0 Hz,
1H), 6.37 (d, J = 15.6 Hz, 1H), 5.52 (t, J = 3.0 Hz, 1H), 4.23 –
4.14 (m, 2H), 3.63 (dd, J = 9.6, 4.8 Hz, 1H), 3.37 (d, J = 3.0 Hz,
1H), 1.23 (t, J = 7.8 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ
172.4, 159.3 (d, JC-F = 244.5 Hz), 147.0, 142.9, 133.2, 129.4 (d,
JC-F = 9.0 Hz), 128.2 (d, JC-F = 4.5 Hz), 127.6 (d, JC-F = 13.5 Hz),
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Ethyl
(E)-2-((2-fluorophenyl)(hydroxy)methyl)-4-(4-
tolyl)but-3-enoate (3bb):
127.5, 126.9, 124.1 (d, JC-F = 4.5 Hz), 123.9, 115.2 (d, JC-F =
21.0 Hz), 68.6, 61.5, 54.9, 14.0; ESI-HRMS calcd. for
(±)-syn-3bb: Yield: 40% (131.3 mg, 0.40 mmol). Colorless
oil. 1H NMR (600 MHz, CDCl3) δ 7.47 (t, J = 7.2 Hz, 1H), 7.26
– 7.18 (m, 3H), 7.09 (dd, J = 7.2, 4.2 Hz, 3H), 7.04 – 6.99 (m,
1H), 6.33 (d, J = 16.2 Hz, 1H), 6.25 (dd, J = 16.2, 9.0 Hz, 1H),
5.44 (t, J = 3.0 Hz,1H), 4.19 – 4.10 (m, 2H), 3.55 (dd, J = 9.0,
4.2 Hz, 1H), 3.35 (d, J = 3.0 Hz, 1H), 2.32 (s, 3H), 1.20 (t, J =
7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 173.1, 159.5 (d, JC-
F = 244.2 Hz), 137.7, 135.4, 133.7, 129.2, 129.1, 128.5 (d, JC-F
= 4.0 Hz), 127.8 (d, JC-F = 12.4 Hz), 126.3, 124.0 (d, JC-F = 3.3
Hz), 121.1, 115.0 (d, JC-F = 21.6 Hz), 68.5, 61.2, 55.2, 21.2, 14.0;
ESI-HRMS calcd. for C20H21FNaO3 ([M+Na]+) 351.1372,
found 351.1368.
C19H18FNNaO5 ([M+Na]+) 382.1067, found 382.1062.
(±)-anti-3db: Yield: 36% (130.0 mg, 0.36 mmol). Pale yel-
1
low solid. H NMR (600 MHz, CDCl3) δ 8.14 (d, J = 9.0 Hz,
2H), 7.47 (t, J = 7.2 Hz, 1H), 7.40 (d, J = 9.0 Hz, 2H), 7.28 –
7.24 (m, 1H), 7.17 (t, J = 7.2 Hz, 1H), 6.98 (t, J =9.0 Hz, 1H),
6.42 (d, J = 15.6 Hz, 1H), 6.37 (dd, J = 15.6, 8.4 Hz, 1H), 5.38
(d, J = 7.2 Hz, 1H), 4.25 – 4.15 (m, 2H), 3.63 (t, J = 8.4 Hz,
1H), 3.24 (s, 1H), 1.24 (t, J = 7.2 Hz, 3H);13C NMR (150 MHz,
CDCl3) δ 172.3, 159.7 (d, JC-F = 244.0 Hz), 147.1, 142.8, 132.4,
129.6 (d, JC-F = 8.2 Hz), 128.2, 128.1 (d, JC-F = 13.0 Hz), 127.6
(d, JC-F = 4.00 Hz), 127.0, 124.4 (d, JC-F = 3.3 Hz), 123.9, 115.3
(d, JC-F = 21.8 Hz), 69.6, 61.5, 56.7, 14.1; ESI-HRMS calcd. for
C19H18FNNaO5 ([M+Na]+) 382.1067, found 382.1065.
(±)-anti-3bb: Yield: 39% (127.5 mg, 0.39 mmol). Pale yel-
low solid. 1H NMR (600 MHz, CDCl3) δ 7.45 (dt, J = 7.2, 1.2
Hz, 1H), 7.27 – 7.20 (m, 1H), 7.19 – 7.11 (m, 3H), 7.07 (d, J =
7.8 Hz, 2H), 7.01 – 6.93 (m, 1H), 6.33 (d, J = 15.6 Hz, 1H),
6.12 (dd, J = 15.6, 9.0 Hz, 1H), 5.34 (t, J = 6.6 Hz, 1H), 4.22 –
4.12 (m, 2H), 3.59 (t, J = 7.8 Hz, 1H), 3.26 (d, J = 6.6 Hz, 1H),
2.31 (s, 3H), 1.22 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz,
CDCl3) δ 173.0, 159.7 (d, JC-F = 244.2 Hz), 137.7, 134.3, 133.7,
129.4 (d, JC-F = 8.3 Hz), 129.2, 128.5 (d, JC-F = 13.2 Hz), 127.8
(d, JC-F = 4.0 Hz), 126.3, 124.2 (d, JC-F = 3.3 Hz), 122.1, 115.2
(d, JC-F = 21.9 Hz), 69.8, 61.2, 56.6, 21.2, 14.1; ESI-HRMS
calcd. for C20H21FNaO3 ([M+Na]+) 351.1372, found 351.1370.
Ethyl (E)-2-((2-fluorophenyl)(hydroxy)methyl)-4-(3-nitro-
phenyl)but-3-enoate (3eb):
(±)-syn-3eb: Yield: 32% (114.7 mg, 0.32 mmol). Colorless
oil. 1H NMR (600 MHz, CDCl3) δ 8.13 (s, 1H), 8.09 - 8.05 (m,
1H), 7.59 (d, J = 7.2 Hz, 1H), 7.46 (q, J = 8.4 Hz, 2H), 7.27 -
7.21 (m, 1H), 7.11 (t, J = 7.2 Hz, 1H), 7.06 – 7.02 (m, 1H), 6.46
(dd, J = 16.2, 9.0 Hz, 1H), 6.36 (d, J = 16.2 Hz, 1H), 5.52 (s,
1H), 4.24 – 4.15 (m, 2H), 3.62 (dd, J = 9.0, 4.2 Hz, 1H), 3.34
(d, J = 1.2 Hz, 1H), 1.24 (t, J = 7.2 Hz, 3H); 13C NMR (150
MHz, CDCl3) δ 172.6, 159.4 (d, JC-F = 244.5 Hz), 148.6, 138.3,
133.0, 132.1, 129.4, 129.4 (d, JC-F = 9.0 Hz), 128.2 (d, JC-F = 4.5
Hz), 127.6 (d, JC-F = 12.0 Hz), 125.8, 124.1 (d, JC-F = 3.0 Hz),
122.3, 121.1, 115.2 (d, JC-F = 21.0 Hz), 68.6, 61.5, 54.8, 14.0;
ESI-HRMS calcd. for C19H18FNNaO5 ([M+Na]+) 382.1067,
found 382.1062.
Ethyl
(E)-4-(4-chlorophenyl)-2-((2-fluorophenyl)(hy-
droxy)methyl)but-3-enoate (3cb):
(±)-syn-3cb: Yield: 28% (97.5 mg, 0.28 mmol). Colorless oil.
1H NMR (600 MHz, CDCl3) δ 7.45 (dt, J = 7.8, 1.8 Hz, 1H),
7.27 – 7.20 (m, 5H), 7.10 (dt, J = 7.2, 0.6 Hz, 1H), 7.02 (dd, J
= 9.0, 0.6 Hz, 1H), 6.31-6.25 (m, 2H), 5.46 (d, J = 4.2 Hz, 1H),
4.20 – 4.13 (m, 2H), 3.58 – 3.54 (m, 1H), 3.33 (s, 1H), 1.21 (t,
J = 7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 172.9, 159.5
(d, JC-F = 244.5 Hz), 135.0, 134.2, 133.5, 129.3 (d, JC-F = 9.0
Hz), 128.7, 128.4 (d, JC-F = 4.5 Hz), 127.7 (d, JC-F = 13.5 Hz),
127.6, 124.1 (d, JC-F = 3.0 Hz), 123.0, 115.1 (d, JC-F = 22.5 Hz),
68.5, 61.3, 55.0, 14.0; ESI-HRMS calcd. for C19H18ClF-
NaO3([M+Na]+) 371.0826, found 371.0824.
(±)-anti-3eb: Yield: 31% (111.1 mg, 0.31 mmol). Colorless
oil. 1H NMR (600 MHz, CDCl3) δ 8.10 (s, 1H), 8.07 (d, J = 9.0
Hz, 1H), 7.58 (d, J = 7.2 Hz, 1H), 7.50 – 7.43 (m, 2H), 7.28 –
7.23 (m, 1H), 7.17 (t, J = 7.2 Hz, 1H), 6.99 (t, J = 9.0 Hz, 1H),
6.41 (d, J = 16.2 Hz, 1H), 6.33 (dd, J = 16.2, 9.0 Hz, 1H), 5.37
(t, J = 6.0 Hz, 1H), 4.24 – 4.17 (m, 2H), 3.63 (t, J = 6.0 Hz, 1H),
3.29 (d, J = 6.0 Hz, 1H), 1.24 (t, J = 7.2 Hz, 3H); 13C NMR (150
MHz, CDCl3) δ 172.4, 159.7 (d, JC-F = 243.0 Hz), 148.6, 138.2,
132.1, 132.1, 129.6 (d, JC-F = 7.5 Hz), 129.4, 128.2 (d, JC-F
=
(±)-anti-3cb: Yield: 28% (98.0 mg, 0.28 mmol). Colorless oil.
1H NMR (600 MHz, CDCl3) δ 7.45 (dt, J = 7.2, 1.2 Hz, 1H),
7.28 – 7.22 (m, 4H), 7.19 (d, J = 8.4 Hz, 1H), 7.17 – 7.13 (dd,
J =7.2,0.6 Hz, 1H), 6.98 (dd, J = 9.6, 0.6 Hz, 1H), 6.31 (d, J =
15.6 Hz, 1H), 6.16 (ddd, J = 15.6, 9.0, 1.2 Hz, 1H), 5.34 (t, J =
6.6 Hz, 1H), 4.24 – 4.13 (m, 2H), 3.58 (t, J = 8.4 Hz, 1H), 3.24
(d, J = 6.6 Hz, 1H), 1.23 (t, J = 7.2 Hz, 3H); 13C NMR (150
13.5 Hz), 127.7 (d, JC-F = 4.5 Hz), 126.7, 124.4 (d, JC-F = 1.5
Hz), 122.4, 121.1, 115.3 (d, JC-F = 22.5 Hz), 69.6, 61.5, 56.5,
14.1; ESI-HRMS calcd. for C19H18FNNaO5 ([M+Na]+)
382.1067, found 382.1062.
Ethyl (E)-2-(hydroxy(phenyl)methyl)-4-(3-nitrophenyl)but-
3-enoate (3ea):
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Page 10 of 13
(±)-syn-3ea: Yield: 24% (81.4 mg, 0.24 mmol). Pale yellow
oil. H NMR (600 MHz, CDCl3) δ 8.17 (s, 1H), 8.07 (dd, J =
127.7 (d, JC-F = 12.0 Hz), 127.3, 125.9, 124.5, 124.1 (d, JC-F
=
1
1
2
3
4
5
6
7
8
4.5 Hz), 121.7, 115.0 (d, JC-F = 21.0 Hz), 68.4 (d, JC-F = 1.5 Hz),
61.3, 55.0, 14.0; ESI-HRMS calcd. for C17H17FNaO3S
([M+Na]+) 343.0780, found 343.0777.
8.4, 1.2 Hz, 1H), 7.63 (d, J = 7.8 Hz, 1H), 7.46 (t, J = 7.8 Hz,
1H), 7.34 (m, 4H), 7.28 (t, J =8.4 Hz, 1H), 6.50 (dd, J = 16.2,
8.4 Hz, 1H), 6.44 (d, J = 16.2 Hz, 1H), 5.16 (d, J = 6.0 Hz, 1H),
4.14 – 4.08 (m, 2H), 3.51 (dd, J = 8.4, 5.4 Hz, 1H), 3.02 (s, 1H),
1.16 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 172.2,
148.6, 140.6, 138.3, 132.7, 132.2, 129.4, 128.3, 128.0, 126.6,
126.3, 122.3, 121.1, 74.4, 61.3, 57.3, 14.0; ESI-HRMS calcd.
for C19H19NNaO5 ([M+Na]+) 364.1161, found 364.1159.
(±)-anti-3ea: Yield: 21% (71.5 mg, 0.21 mmol). Pale oil. 1H
NMR (600 MHz, CDCl3) δ 8.09 (s, 1H), 8.06 (d, J = 8.4 Hz,
1H), 7.53 (d, J = 7.8 Hz, 1H), 7.43 (t, J = 7.8 Hz, 1H), 7.38 –
7.32 (m, 4H), 7.29 (dt, J = 8.4, 4.2 Hz, 1H), 6.37 (d, J = 16.2
Hz, 1H), 6.23 (dd, J = 16.2, 9.0 Hz, 1H), 5.05 (dd, J = 8.4, 5.4
Hz, 1H), 4.26 – 4.19 (m, 2H), 3.60 (t, J = 8.4 Hz, 1H), 3.02 (d,
J = 5.4 Hz, 1H), 1.27 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz,
CDCl3) δ 172.5, 148.6, 140.9, 138.2, 132.1, 132.0, 129.4, 128.5,
128.2, 127.0, 126.4, 122.3, 121.0, 75.5, 61.4, 57.1, 14.1; ESI-
HRMS calcd. for C19H19NNaO5 ([M+Na]+) 364.1161, found
364.1158.
(±)-anti-3gb: Yield: 38% (121.2 mg, 0.38 mmol). Yellow oil.
1H NMR (600 MHz, CDCl3) δ 7.37 (t, J = 7.2 Hz, 1H), 7.21 –
7.13 (m, 1H), 7.12 – 7.03 (m, 2H), 6.91 J = 9.0 Hz, 1H), 6.83-
6.78 ( m, 2H), 6.42 (d, J = 15.6 Hz, 1H), 5.93 (dd, J = 15.6, 9.0
Hz, 1H), 5.24 (d, J = 6.6 Hz, 1H), 4.14 – 4.05 (m, 2H), 3.48 (t,
J = 8.4 Hz, 1H), 3.26 (s, 1H), 1.14 (t, J = 7.2 Hz, 3H); 13C NMR
(150 MHz, CDCl3) δ 172.7, 159.8 (d, JC-F = 244.5 Hz), 141.4,
129.4 (d, JC-F = 7.5 Hz), 128.4 (d, JC-F = 12.0 Hz), 127.7 (d, JC-
F = 4.5 Hz), 127.4, 127.2, 125.9, 124.5, 124.2 (d, JC-F = 3.0 Hz),
122.6, 115.2 (d, JC-F = 22.5 Hz), 69.7, 61.2, 56.3, 14.0; ESI-
HRMS calcd. for C17H17FNaO3S ([M+Na]+) 343.0780, found
343.0786.
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23
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Ethyl
(E)-2-((2-fluorophenyl)(hydroxy)methyl)-4-phe-
nylpent-3-enoate (3hb):
(±)-syn-3hb: Yield: 38% (124.7 mg, 0.38 mmol). Pale yellow
oil. 1H NMR (600 MHz, CDCl3) δ 7.48 (t, J = 7.8 Hz, 1H), 7.28-
7.26 (m, 4H), 7.23 – 7.21 (m, 2H), 7.09 (t, J = 7.8 Hz, 1H), 6.98
(t, J = 9.6 Hz,1H), 5.93 (d, J = 9.6 Hz, 1H), 5.53 (s, 1H), 4.19
– 4.13 (m, 2H), 3.83 (dd, J = 9.6, 3.6 Hz, 1H), 3.55 (s, 1H), 1.71
(s, 3H), 1.22 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3)
δ 173.6, 159.4 (d, JC-F = 243.0 Hz), 143.1, 140.9, 128.9 (d, JC-F
= 7.5 Hz), 128.4 (d, JC-F = 4.5 Hz), 128.1, 128.0 (d, JC-F = 12.0
Hz), 127.2, 125.8, 123.9 (d, JC-F = 3.0 Hz), 119.9, 114.8 (d, JC-F
= 22.5 Hz), 68.5, 61.15, 50.6, 16.1, 14.0; ESI-HRMS calcd. for
C20H21FNaO3 ([M+Na]+) 351.1372, found 351.1377.
Ethyl (E)-2-((2-fluorophenyl)(hydroxy)methyl)-4-(naphtha-
len-1-yl)but-3-enoate (3fb):
(±)-syn-3fb: Yield: 36% (131.2 mg, 0.36 mmol). Yellow
solid. 1H NMR (600 MHz, CDCl3) δ 7.81 (d, J = 7.8 Hz, 1H),
7.75 (d, J = 8.4 Hz, 2H), 7.53 (t, J = 7.8 Hz, 1H), 7.49 (t, J =
7.2 Hz, 1H), 7.46-7.39 (m, 3H), 7.28-7.25 ( m, 1H), 7.11 (t, J =
7.8 Hz, 1H), 7.07 (dd, J = 10.8, 8.4 Hz, 1H), 7.01 (d, J = 15.6
Hz, 1H), 6.29 (dd, J = 15.6, 9.6 Hz, 1H), 5.57 (d, J = 3.6 Hz,
1H), 4.23 (q, J = 7.2 Hz, 2H), 3.72 (dd, J = 9.6, 4.2 Hz, 1H),
3.47 (s, 1H), 1.28 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz,
CDCl3) δ 173.3, 158.4 (d, JC-F = 244.5 Hz), 134.5, 133.4, 133.1,
131.0, 129.1 (d, JC-F = 9.0 Hz), 128.5 (d, JC-F = 4.5 Hz), 128.4,
128.1, 127.1 (d, JC-F = 12.0 Hz), 125.9, 125.7, 125.5, 125.3,
124.1 (d, JC-F = 3.0 Hz), 124.1, 123.8, 115.0 (d, JC-F = 21.00 Hz),
68.5, 61.4, 55.1, 14.1; ESI-HRMS calcd. for C23H21FNaO3
([M+Na]+) 387.1372, found 387.1374.
(±)-anti-3hb: Yield: 38% (124.3 mg, 0.38 mmol). Pale yel-
low oil. 1H NMR (600 MHz, CDCl3) δ 7.50 (t, J = 7.2 Hz, 1H),
7.29 – 7.19 (m, 6H), 7.14 (t, J = 7.2 Hz, 1H), 6.98 (t, J = 9.6
Hz, 1H), 5.74 (d, J = 9.6 Hz, 1H), 5.34 (t, J = 6.0 Hz,1H), 4.18
(d, J = 6.0 Hz, 2H), 3.85 (t, J = 9.6 Hz, 1H), 3.26 (d, J = 4.8
Hz, 1H), 1.80 (s, 3H), 1.24 (t, J = 7.2 Hz, 3H); 13C NMR (150
MHz, CDCl3) δ 173.3, 159.9 (d, JC-F = 244.5 Hz), 143.0, 134.0,
129.4 (d, JC-F = 9.0 Hz), 128.6 (d, JC-F = 12.0 Hz), 128.2, 128.0
(d, JC-F = 3.0 Hz), 127.2, 125.9, 124.2 (d, JC-F = 3.0 Hz), 121.0,
115.2 (d, JC-F = 21.0 Hz), 69.7, 61.1, 53.1, 16.2, 14.1; ESI-
HRMS calcd. for C20H21FNaO3 ([M+Na]+) 351.1372, found
351.1378.
(±)-anti-3fb: Yield: 33% (120.1 mg, 0.33 mmol). White solid.
1H NMR (600 MHz, CDCl3) δ 7.80 (d, J = 7.8 Hz, 1H), 7.73
(dd, J = 13.2, 7.8 Hz, 2H), 7.52 (dt, J = 7.2, 1.2 Hz, 1H), 7.46 -
7.38 (m, 4H), 7.28 – 7.24 (m, 1H), 7.18 (t, J = 7.2 Hz, 1H),7.03
(d, J = 15.6 Hz, 1H), 6.99 (d, J = 9.0 Hz, 1 H), 6.14 (ddd, J =
15.0, 9.0, 1.2 Hz, 1H), 5.43 (d, J = 7.8 Hz, 1H), 4.25 (q, J = 7.2
Hz, 2H), 3.75 (t, J = 9.0 Hz, 1H), 3.21 (s, 1H), 1.28 (t, J = 7.2Hz,
Ethyl (E)-2-(hydroxy(phenyl)methyl)-4-phenylpent-3-enoate
(3ha):
(±)-syn-3ha: Yield: 25% (77.4 mg, 0.25 mmol). Pale yellow
3H); 13C NMR (150 MHz, CDCl3) δ 172.9, 160.0 (d, JC-F
=
1
oil. H NMR (400 MHz, CDCl3) δ 7.49 – 7.20 (m, 10H), 5.96
244.5 Hz), 134.4, 133.4, 132.3, 131.0, 129.5 (d, JC-F = 9.0 Hz),
128.5 (d, JC-F = 13.5 Hz), 128.4, 128.1, 128.0 (d, JC-F = 4.5 Hz),
126.3, 125.9, 125.7, 125.6, 124.4 (d, JC-F = 3.0 Hz), 124.1, 123.7,
115.4 (d, JC-F = 22.5 Hz), 69.8, 61.3, 57.3, 14.2; ESI-HRMS
calcd. for C23H21FNaO3 ([M+Na]+) 387.1372, found 387.1369.
(d, J = 9.6 Hz, 1H), 5.15 (d, J = 4.4 Hz, 1H), 4.10 (dt, J = 6.8,
1.2 Hz, 2H), 3.71 (ddd, J = 10.0, 5.2, 1.2 Hz, 1H), 3.11 (s, 1H),
1.81 (s, 3H), 1.16 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 173.1, 143.0, 140.9, 140.8, 128.2, 128.1, 127.7, 127.3,
126.4, 125.9, 120.7, 74.7, 61.0, 53.4, 16.3, 14.0; ESI-HRMS
calcd. for C20H22NaO3 ([M+Na]+) 333.1467, found 333.1465.
Ethyl (E)-2-((2-fluorophenyl)(hydroxy)methyl)-4-(thiophen-
2-yl)but-3-enoate (3gb):
(±)-anti-3ha: Yield: 29% (89.9 mg, 0.29 mmol). Pale yellow
oil. 1H NMR (400 MHz, CDCl3) δ 7.36 (d, J = 7.2 Hz, 2H), 7.31
(t, J = 7.2 Hz, 2H), 7.26 (d, J = 6.0 Hz, 3H), 7.21 (t, J = 7.6 Hz,
3H), 5.67 (d, J = 10.0 Hz, 1H), 4.99 (d, J = 8.4 Hz, 1H), 4.21 (q,
J = 7.2 Hz, 2H), 3.76 (t, J = 9.6 Hz, 1H), 2.98 (s, 1H), 1.71 (s,
3H), 1.27 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
173.4, 143.1, 141.4, 140.0, 128.2, 128.1, 127.9, 127.2, 126.6,
125.9, 121.5, 75.6, 61.1, 54.0, 16.2, 14.2. ESI-HRMS calcd. for
C20H22NaO3 ([M+Na]+) 333.1467, found 333.1464.
(±)-syn-3gb: Yield: 34% (108.8 mg, 0.34 mmol). Yellow oil.
1H NMR (600 MHz, CDCl3) δ 7.47 (t, J = 7.2 Hz, 1H), 7.25 -
7.21 (m, 1H), 7.13 (d, J = 4.8 Hz, 1H), 7.10 (t, J = 7.2 Hz, 1H),
7.03 - 6.99 (m, 1H), 6.91 (t, J = 4.8 Hz, 1H), 6.87 (d, J = 3.0
Hz, 1H), 6.48 (d, J = 15.6 Hz, 1H), 6.13 (dd, J = 15.6, 9.0 Hz,
1H), 5.43 (d, J = 4.2 Hz, 1H), 4.19 – 4.09 (m, 2H), 3.52 (dd, J
= 9.0, 4.2 Hz, 1H), 3.35 (s, 1H), 1.20 (t, J = 7.2 Hz, 3H); 13C
NMR (150 MHz, CDCl3) δ 172.8, 159.5 (d, JC-F = 243.0 Hz),
141.5, 129.2 (d, JC-F = 7.5 Hz), 128.5 (d, JC-F = 6.0 Hz), 128.4,
Preparation for tetrahydrofuran
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The Journal of Organic Chemistry
(±)-4: A mixture of (±)-anti-3ap (310.3 mg, 1.25 mmol) and
the combined organic layers were washed with brine (1 × 5 mL),
then dried (MgSO4) and filtered. The filtrate was concentrated
in vacuo and the resulting residue was purified by flash column
chromatography [silica gel, EtOAc/PE 1:50] to give the ex-
pected ethyl 2-ethyl-5-phenylfuran-3-carboxylate 7 (116 mg,
0.48 mmol), Yield: 95%.
1
2
3
4
5
6
7
8
NBS (445 mg, 2.5 mmol) in DCM (13 mL) was stirred at rt
under argon for 4 hours. The reaction mixture was concentrated
in vacuo and the resulting residue was purified by column chro-
matography [silica gel, EtOAc/PE 1:10] to give the expected
(±)-4 (376 mg, 1.15 mmol), Yield: 92% (dr = 1:10). Major iso-
1
mer: H NMR (600 MHz, CDCl3) δ 7.46 (d, J = 7.8 Hz, 2H),
Method B: To a solution of (±)-6 (123 mmol, 0.5 mmol) in
toluene (1 mL) was added a solution of DDQ (136.2 mg, 0.6
mmol) in toluene (1 mL) dropwisely, and the mixture was
stirred at reflux for 2 h. Upon completion as indicated by TLC,
the mixture was poured into H2O (5 mL), and separated. The
aqueous layer was extracted with ethyl acetate (2 × 10 mL), and
the combined organic layers were washed with brine (1 × 5 mL),
then dried (MgSO4) and filtered. The filtrate was concentrated
in vacuo and the resulting residue was purified by flash column
chromatography [silica gel, EtOAc/PE 1:50] to give the ex-
pected ethyl 2-ethyl-5-phenylfuran-3-carboxylate 7 (112 mg,
0.46 mmol), Yield: 92%.
7.38 (t, J = 7.2 Hz, 2H), 7.34 (t, J = 7.2 Hz, 1H), 4.98 (d, J =
8.4 Hz, 1H), 4.35 (dt, J = 9.0, 1.8 Hz, 1H), 4.29 (m, 1H), 4.23
(q, J = 7.2 Hz, 2H), 3.22 – 3.17 (dt, J = 9.0,7.2 Hz, 1H), 1.80
(m, 1H), 1.30 (t, J = 7.2 Hz, 3H), 1.04 (t, J = 7.2 Hz, 3H); 13
C
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
NMR (100 MHz, CDCl3) δ 170.5, 137.9, 128.5, 126.5, 86.3,
82.7, 61.5, 59.7, 53.7, 52.5, 28.4, 14.1, 9.6; ESI-HRMS calcd.
for C15H19BrNaO3 ([M+Na]+) 349.0415, found 349.0411.
Preparation for 2,5-dihydrofuran
(±)-5: A mixture of (±)-4 (167 mg, 0.51 mmol) and DBU (77
μL, 0.51 mmol) in DCM (13 mL ) was stirred at rt under argon
atmosphere for 4 h. The reaction mixture was concentrated in
vacuo and the resulting residue was purified by column chro-
matography [silica gel, EtOAc/PE 1:50] to give the expected
ethyl cis-2-ethyl-5-phenyl-2,5-dihydrofuran-3-carboxylate (±)-
Colorless oil. 1H NMR (600 MHz, CDCl3) δ 7.56 (d, J = 7.8
Hz, 2H), 7.29 (t, J = 7.8 Hz, 2H), 7.18 (t, J = 7.8 Hz, 1H), 6.80
(s, 1H), 4.23 (q, J = 7.2 Hz, 2H), 3.00 (q, J = 7.2 Hz, 2H), 1.29
(t, J = 7.2 Hz, 3H), 1.24 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz,
CDCl3) δ 163.9, 163.4, 151.6, 130.2, 128.7, 127.6, 123.6, 114.5,
105.5, 60.1, 21.3, 14.3, 12.3; ESI-HRMS calcd. for C15H16NaO3
([M+Na]+) 267.0997, found 267.0994.
1
5 (108 mg, 0.44 mmol), Yield: 86%. Colorless oil. H NMR
(300 MHz, CDCl3) δ 7.33 (m, 5H), 6.78 (t, J = 1.8 Hz, 1H), 5.90
(dd, J = 6.0, 1.5 Hz, 1H), 5.35 – 5.22 (m, 1H), 4.22 (qd, J = 7.2,
1.8 Hz, 2H), 2.06–1.68 (m, 2H), 1.29 (t, J = 7.2 Hz, 3H), 1.00
(t, J = 7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 162.9, 141.2,
140.5, 135.0, 128.7, 128.2, 126.4, 87.0, 86.4, 60.6, 27.4, 14.1,
9.0; ESI-HRMS calcd. for C15H18O3Na ([M+Na]+) 269.1154,
found 269.1148.
ASSOCIATED CONTENT
Supporting Information
X-Ray crystallography data and NMR spectra. This material is
available free of charge via the Internet at http://pubs.acs.org.
Preparation for 2,3-dihydrofuran
(±)-6:
AUTHOR INFORMATION
Corresponding Author
Method A: A mixture of (±)-4 (167 mg, 0.51 mmol), DBU
(77 μL, 0.51 mmol) and H2O (18.4 μL, 1.02 mmol) in DCM (13
mL) was stirred at reflux for 8 h. The reaction mixture was con-
centrated and the resulting residue was purified by column chro-
matography [silica gel, EtOAc/PE 1:50] to give the expected
ethyl trans-2-ethyl-5-phenyl-2,3-dihydrofuran-3-carboxylate
(±)-6 (103 mg, 0.42 mmol), Yield: 82%.
ychai@snnu.edu.cn (Y. Chai)
qiqizhang@snnu.edu.cn(Q. Zhang)
Notes
Any additional relevant notes should be placed here.
Method B: A mixture of (±)-5 (126 mg, 0.51 mmol), DBU
(77 μL, 0.51 mmol) and H2O (18.4 μL, 1.02 mmol) in DCM (13
mL) was stirred at reflux for 8 h. The reaction mixture was con-
centrated and the resulting residue was purified by column chro-
matography [silica gel, EtOAc/PE 1:50] to give the expected
ethyl trans-2-ethyl-5-phenyl-2,3-dihydrofuran -3-carboxylate
(±)-6 (112 mg, 0.46 mmol), Yield: 89%.
Colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.58 (d, J = 6.8
Hz, 2H), 7.32 (d, J = 7.6 Hz, 3H), 5.33 (s, 1H), 4.93 (q, J = 12.5,
6.0 Hz, 1H), 4.19 (q, J = 6.8 Hz, 2H), 3.59 (d, J = 6.4 Hz, 1H),
169-1.86 (m, 2H), 1.28 (t, J = 7.2 Hz, 3H), 1.05 (t, J = 7.2 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 170.6, 137.9, 128.6, 128.5,
126.52 86.4, 82.8, 61.5, 59.7, 52.6, 28.4, 14.2, 9.6; ESI-HRMS
calcd. for C15H19O3 ([M+H]+) 247.1329, found 247.1332.
ACKNOWLEDGMENT
This work was supported by the National Natural Science Founda-
tion of China (No. 21472119, 21302119), Ministry of Science and
Technology (No. 2012ZX09502-001-001) and the Fundamental
Research Funds for the Central Universities (GK201603036,
GK201701002). All of the financial support are gratefully
acknowledged.
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Method A: To a solution of (±)-5 (123 mmol, 0.5 mmol) in
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