Asymmetric Construction of α-Substituted β-Hydroxy Lactones via Ni Catalyzed Decarboxylative Addition Reaction

Article abstract of DOI:10.1021/acs.joc.0c02854

We described a Ni-bidentate oxazoline catalyzed highly enantio- and diastereoselective decarboxylative aldol reaction of 2-oxotetrahydrofuran-3-carboxylic acid/2-oxochromane-3-carboxylic acid derivatives with different kinds of carbonyls. Under optimal reaction conditions, α-substituted β-hydroxy butyrolactones and dihydrocoumarins with an all-carbon quaternary stereocenter have been generated with high levels of functional-group compatibility. Furthermore, proficient transformations of products were also described, in which an aliphatic tertiary alcohol and a multi-substituted 1,4-diol were smoothly constructed through hydrogenation and ring-opening reaction, respectively.

Full text of DOI:10.1021/acs.joc.0c02854

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Note
Asymmetric Construction of α‑Substituted β‑Hydroxy Lactones via
Ni Catalyzed Decarboxylative Addition Reaction
Lingchen He, Ebrahim-Alkhalil M. A. Ahmed, Hongxin Liu, Xingen Hu,* Hong-ping Xiao, Juan Li,
and Jun Jiang*
Cite This: J. Org. Chem. 2021, 86, 4825−4834
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ABSTRACT: We described a Ni-bidentate oxazoline catalyzed highly enantio- and diastereoselective decarboxylative aldol reaction
of 2-oxotetrahydrofuran-3-carboxylic acid/2-oxochromane-3-carboxylic acid derivatives with different kinds of carbonyls. Under
optimal reaction conditions, α-substituted β-hydroxy butyrolactones and dihydrocoumarins with an all-carbon quaternary
stereocenter have been generated with high levels of functional-group compatibility. Furthermore, proficient transformations of
products were also described, in which an aliphatic tertiary alcohol and a multi-substituted 1,4-diol were smoothly constructed
through hydrogenation and ring-opening reaction, respectively.
nantioenriched butyrolactones1 and dihydrocoumarins2
specifically α-functionalized scaffolds symbolize significant
lactone moieties which are wildly found in natural products and
pharmaceuticals as exemplified by microtermolides B,3 virginiae
butanolides,4 and salprzelactone5 (Figure 1). Besides, they are
Scheme 1. Catalytic Asymmetric Synthesis of α-Substituted
Cyclic Esters
E
Figure 1. Natural products and pharmaceuticals containing chiral cyclic
ester moieties.
also versatile building blocks for the synthesis of alcohols with
great structure diversity via ring-opening reactions.6 Thus, the
exploration of efficient methods to construct enantioenriched
lactones becomes an attractive target in organic synthesis.
Obviously, the direct catalytic asymmetric α-functionalization
of lactones would be an ideal approach to enantioenriched α-
substituted lactones. However, it is a very challenging task due to
the high pKa value of lactones’ α-proton, which makes them
difficult to enolize under mild conditions; besides, the ring-
opening possibility of a cyclic ester moiety brings additional
difficulties to the target. Accordingly, multiple operations were
always required for the asymmetric synthesis of α-substituted
lactones, and attempts to develop catalytic asymmetric method-
ologies for this target were mainly focused on Mukaiyama-type
addition reactions (Scheme 1, eq 1)7 or functional group
transformation of multi-substituted lactones (Scheme 1, eqs 2
and 3).6a
Hence, developments of direct catalytic α-functionalizations
of lactones are constantly in high demand, which may provide a
general and convenient access to versatile α-substituted lactones
Received: December 1, 2020
Published: February 26, 2021
https://dx.doi.org/10.1021/acs.joc.0c02854
© 2021 American Chemical Society
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a
Table 1. Optimization of Reaction Conditions
b
c
c
entry
catalyst
solvent
T (°C/h)
yield (%)
ee (%)
dr
1:1
1
2
3
4
5
6
7
8
9
Cu(OAc)2
Ni(OAc)2·4H2O
[Ni]/L1
[Ni]/L2
[Ni]/L3
[Ni]/L4
[Ni]/L5
[Ni]/L5
[Ni]/L5
THF
THF
THF
THF
THF
THF
THF
EtOH
EtOH
60/24
60/24
10/72
10/72
10/72
10/72
10/72
10/72
0/72
20
33
38
79
52
53
57
78
70
1.2:1
1:1
16
63
81
76
92
99
98
6.6:1
1.3:1
1.4:1
1.5:1
7:1
7.1:1
a
General reaction conditions: 1 (0.2 mmol), 2a (0.1 mmol), ligand (22 mol %), and catalyst (20 mol %) in 1 mL of solvent at a specific
b
c
temperature for a specific time. Isolated yield of major diastereoisomer. Determined by chiral HPLC analysis. [Ni] = Ni(OAc)2·4H2O.
from simple starting materials. However, related studies were
rarely reported so far.
commenced with exploring the catalytic ability of different metal
salts in the decarboxylative aldol reaction of 1 and isopropyl (E)-
2-oxo-4-phenylbut-3-enoate 2a. Different Lewis acids such as
Cu(OAc)2 and Ni(OAc)2·4H2O were evaluated in THF at 60
°C (for the full evaluation of metal salts, see the Supporting
Information). Fortunately, the desired decarboxylative addition
product 3a was obtained in 20% yield and 1:1 dr in 24 h when 20
mol % of Cu(OAc)2 was employed as catalyst (entry 1, Table 1),
while Zn(OTf)2, MnSO4, and FeCl3 failed to give any product.
Noticeably, Ni(OAc)2·4H2O exhibited the best catalytic ability
and resulted in product 3a with higher yield and diastereose-
lectivity (entry 2). Next, the effects of different chiral oxazoline
ligands were studied (for the full evaluation of ligands, see the
Supporting Information). Generally, improvements in reaction
performance were always observed when oxazoline ligands were
added in the reaction. It is worth noting that the introduction of
a pyridine moiety to the bidentate oxazoline ligand brought a
good effect on diastereoselectivity (entry 4), while bidentate
oxazoline ligands with bulky substituents on the methylene
carbon exhibited better enantiocontrol (entries 5−7). Notice-
ably, bidentate oxazoline L5 bearing a 5F-benzyl group afforded
the desired product with the highest enantioselectivity, albeit
with poor diastereoselectivity (entry 7). To improve the result,
further optimization of reaction conditions was carried out by
employing L5 as ligand (for the full evaluation of solvents,
temperature, and additives, see the Supporting Information). It
was revealed that solvent played an important role in
stereocontrol, while the addition of organic or inorganic base
decreased the reaction conversion as well as enantioselectivity.
Finally, the best result was obtained when the reaction was
conducted in EtOH at 10 °C for 72 h (entry 8, 78% yield, 99%
ee, 7:1 dr).
Inspired by nature’s way to synthesize polyketide and fatty
acids,8 we are particularly interested in catalytic asymmetric
decarboxylative addition reactions for the synthesis of chiral
carboxylic acid derivatives. Since Shair et al. reported the
asymmetric decarboxylative aldol reaction of methylmalonic
acid half-thioester and aldehydes in 2005,9 β-keto acids, malonic
acid half-thioesters (MAHTs), and 2-cyanoacetic acid have been
successfully employed in decarboxylative addition reactions.10
In contrast, malonic acid and malonic acid half-oxyesters
(MAHOs), which can act as nucleophilic equivalents of acetic
acid/ester via decarboxylation process, remain largely unex-
plored and unexploited in catalytic asymmetric decarboxylative
additions due to their poorer nucleophilic abilities.11,12
Recently, we made our initial efforts to address this problem:
in the promotion of Ni-oxazoline complexes, we successfully
achieved novel catalytic asymmetric decarboxylative aldol
reactions of malonic acid and half-oxyesters with various
carbonyls.13
Encouraged by these results as well as the importance of chiral
α-substituted lactones, two types of nucleophilic cyclic esters
surrogates, 2-oxotetrahydrofuran-3-carboxylic acid (OTHF-
CA)14 and 2-oxochromane-3-carboxylic acid as (OCCA)),15
were designed as potential decarboxylative donors for the
construction of α-substituted cyclic esters. Herein, we report a
nickel-oxazoline complex catalyzed highly enantio- and
diastereoselective decarboxylative aldol reaction of OTHFCA/
OCCA with various carbonyls, affording a facile access to α-
substituted β-hydroxy lactones in good yield with high
stereoselectivity (Scheme 1, eq 4).
OTHFCA 1 was readily synthesized according to the previous
literature.14 With this cyclic ester precursor in hand, our research
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With the optimal conditions in hand, the versatility of this
reaction was examined with respect to carbonyl substrates by
using 1 as donor, as described in Scheme 2. First, we studied the
Scheme 3. Catalytic Asymmetric Decarboxylative Aldol
Reaction of OCCA 4 and (E)-2-oxo-4-arylbut-3-enoates 2
a
Scheme 2. Catalytic Asymmetric Decarboxylative Aldol
Reaction of OTHFCA 1 and (E)-2-oxo-4-arylbut-3-enoates
a
2
a
General reaction conditions: 4 (0.2 mmol), 2 (0.1 mmol), L5 (22
mol %), and Ni(OAc)2·4H2O (20 mol %) in 1 mL of mixed solvents
(TFEA·EtOH = 9:1) at a specific temperature for 72 h; given are
isolated yield of major diastereoisomer. ee was determined by chiral
b
c
HPLC analysis. Reaction was carried out at 20 °C. Reaction was
carried out at 30 °C.
a
General reaction conditions: 1 (0.2 mmol), 2 (0.1 mmol), L5 (22
mol %), and Ni(OAc)2·4H2O (20 mol %) in 1 mL of EtOH at a
specific temperature for 72 h; given are isolated yields of major
diastereoisomer. ee was determined by chiral HPLC analysis.
Information). With these optimized conditions in hand, we next
examined the substrate scope, and a series of OCCAs as well as
(E)-2-oxo-4-arylbut-3-enoates were employed. As shown in
Scheme 3, different functional groups on carbonyl acceptors 2
were well tolerated and afforded the desired products in good to
excellent yields with high stereoselectivities in most cases (5a−
5g, 59−83%, 7:1−10:1 dr, 92−98% ee). However, the
substituents of OCCAs had an obvious influence on reaction
results. For example, OCCA with a methoxyl group at the 8-
position led to a decreased enantio- and diastereoselectivity
value of product 5i, while the 7-substituted one afforded the
desired product in satisfactory result (5j, 75%, 7:1 dr, 95% ee).
Additionally, 4-nitrobenzaldehyde and isatin also fit well
under modified conditions. In the presence of 20 mol % Ni (II)-
L3 complex, 4-nitrobenzaldehyde 6 and OTHFCA 1 were
smoothly converted into 3-(hydroxy(4-nitrophenyl)methyl)-
dihydrofuran-2(3H)-one 7 in 52% yield (major diastereomer)
with high enantioselectivity, albeit with 1.3:1 dr (Scheme 4).
When isatin acted as electrophile, 3-hydroxy-3-(2-oxotetrahy-
drofuran-3-yl)indolin-2-one was constructed with higher
reaction conversion as well as stereoselectivity (major
diastereomer, 87%, 7:1 dr, 96% ee). Unfortunately, other
aldehydes than nitro-substituted ones exhibited low reactivities,
while activated ketones such as α-keto esters and 1H-indene-
1,2(3H)-dione failed to give any products under the present
reaction conditions.
b
c
Reaction was carried out at 10 °C. Reaction was carried out at 20
d
°C. X-ray structure of 3h (ellipsoid contour at 30% probability).
effect of the ester moiety of 2 and found that changing iPr to Me
or Et brought little influence on the reaction conversion as well
as stereoselectivities. As a result, both 2b and 2c gave the desired
products 3b and 3c with good yields, diastereoselectivities and
excellent enantioselectivities. Subsequently, aryl substituents of
2 were also examined. It was shown that placing various
functional groups on the aromatic ring had very limited effect on
the reaction outcomes: isopropyl (E)-2-oxo-4-arylbut-3-enoate
bearing either an electron-donating or an electron-withdrawing
group on different positions of the benzene ring generally
furnished products in high yields and stereoselectivities (3d−
3m, 71−83%, 6:1−7:1 dr, 98−99% ee). The absolute
configuration of product 3h was assigned as (S,S)-configuration
by X-ray analysis (CCDC 2035137; see the Supporting
Information).
Further application of this asymmetric decarboxylative aldol
reaction was carried out by employing OCCAs as reactants.
However, the desired product 5a was obtained in moderate yield
and enantioselectivity and low diastereoselectivity when the
reaction of 4a and 2a was carried out under the standard
conditions described in Scheme 2. To improve the reaction
outcomes, a careful evaluation of solvents was next conducted,
which revealed that binary solvents of TFEA/EtOH (9/1) could
dramatically enhance the reaction outcomes, leading to 5a in
79% yield, 7:1 dr, and 98% ee (Scheme 3, product 5a; for further
details of screening optimal conditions, see the Supporting
Noticeably, a 5 mmol scale catalytic procedure was performed
in this reaction. As shown in Scheme 5, treatment of OTHFCA 1
(1.3 g, 10 mmol) with isopropyl (E)-4-(4-chlorophenyl)-2-
oxobut-3-enoate (1.26 g, 5 mmol) in the promotion of 10 mol %
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Scheme 4. Catalytic Asymmetric Decarboxylic Aldol
Reaction of OTHFCA 1 and Different Carbonyls
Scheme 7. Plausible Mechanism of Asymmetric
Decarboxylative Aldol Reaction
a
a
Isolated yield for 0.1 mmol scale reaction.
Scheme 5. 5 mmol-Scale Catalytic Procedure
Ni-L5 catalyst led to the corresponding product 3i in high yield
and enantioselectivity (for major diastereomer, 84%, 96% ee).
To demonstrate the synthetic utilities of our methodology,
further transformations of obtained adducts were next carried
out, as underlined in Scheme 6. For example, in the presence of
ability of ligand L5 exhibited in this aldol-decarboxylation
transformation, we suppose that the introduction of electron-
deficient pentafluorobenzyls into oxazoline may obviously affect
C−H/π interactions in catalytic transition states,20 thus
enabling a better stereochemical model and affording the
desired products in high stereoselectivity. To gain more insight
into this decarboxylative process, the high resolution mass
spectroscopy (HRMS) analysis of the reaction between 1 and
isopropyl (E)-4-(3-fluorophenyl)-2-oxobut-3-enoate was car-
ried out. Under standard conditions, two peaks at m/z
1089.1777 and 1091.1844 were observed, indicating inter-
mediates (IV) and (V) were reasonable.
Scheme 6. Transformation of α-Substituted β-Hydroxy
Butyrolactone Products
In summary, a highly enantioselective generation of α-
substituted butyrolactones and dihydrocoumarins with an all-
carbon quaternary stereocenter has been realized. The newly
decarboxylative aldol reaction of OTHFCA/OCCA took place
smoothly with a variety of carbonyl electrophiles via Ni-
bidentate oxazoline catalysis under mild conditions. The
afforded results demonstrated high levels of functional-group
compatibility attainable with this method. Remarkably, the
resulting adducts can be smoothly converted into corresponding
chiral alcohol derivatives through simple operations. Thus, the
present method provides access to synthetically relevant
building blocks with a fully substituted carbon stereocenter
that was hitherto difficult to prepare in enantioenriched form.
Further researches toward broadening this methodology are
currently underway in our laboratory.
Pd/C (10% w/w), 3d can be smoothly reduced to a aliphatic
tertiary alcohol 10 with a dihydrofuran-2(3H)-one substituent
in high yield and enantioselectivity. Besides, AlCl3 catalyzed
ring-opening reaction of adduct 3i by N-methylaniline afforded
multi-substituted 1,4-diol 11 with good yield and maintained
enantioselectivity.
On the basis of previous work13b and obtained results herein, a
nickel catalyzed aldol-decarboxylation mechanism was pro-
posed. As shown in Scheme 7, OTHFCA was efficiently
activated by Ni-bidentate oxazoline catalyst via nickel-
dicarbonyl interaction (I), thus affording the nucleophilic
intermediate (II) after enolization and deprotonation; sub-
sequently, intermediate (II) enantioselectively attacked carbon-
yl acceptors 2 from the Si face and produced corresponding
aldol-type adducts, which then cleaved CO2 to produce the
desired α-substituted β-hydroxy with an (S,S)-configuration.
The fact that higher yield and stereoselectivity were obtained
when EtOH was employed as solvent suggested EtOH may not
only play an important role in the H-transfer step18 but also act
as ligand/hydrogen-bond donor to stabilize the catalytic
transition state.19 As regards the outstanding enantiocontrol
EXPERIMENTAL SECTION
■
General Information. Chemicals were received from commercial
sources without further purification or prepared by literature methods.
1H NMR and 13C NMR spectra were measured on a 500 MHz Bruker
spectrometer, using CDCl3, DMSO, or acetone as the solvent with
tetramethylsilane (TMS) as the internal standard at room temperature.
1
Data for H NMR are reported as follows: chemical shift (δ ppm),
multiplicity, integration, and coupling constant (Hz). Data for 13C
NMR are reported in terms of chemical shift (δ ppm), multiplicity, and
coupling constant (Hz). HRMS (Micromass GCTMS) spectra were
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recorded on a P-SIMS-Gly of Bruker Daltonics Inc. HPLC analysis was
performed on a Shimdzu LC-20A. Chiralpak AS, AD, OD, were
purchased from Daicel Chemical Industries, Ltd. X-ray crystallographic
analysis was performed at the Bruker D8 Venture X-ray single crystal
diffractometer, at Shanghai Institute of Organic Chemistry (SIOC),
Chinese Academy of Sciences (CAS). Organic solutions were
concentrated under reduced pressure on a Buchi rotary evaporator.
Flash column chromatographic purification of products was accom-
plished using forced-flow chromatography on silica gel (300−400
mesh).
General Procedure for the Synthesis of 2-Oxotetrahydrofur-
an-3-carboxylic Acid (OTHFCA) 1.14 The 2-oxotetrahydrofuran-3-
carboxylic acid (OTHFCA) was prepared as follows: Under a N2
atmosphere, triethylamine hydrobromide (1.4 g, 7.7 mmol) was added
to a solution of cyclopropane-1,1-dicarboxylic acid (1 g, 7.7 mmol) in
CH3CN (20 mL). The mixture was heated to 75 °C in an oil bath and
left overnight (16 h) until the reaction completed. Afterward, the
reaction mixture was evaporated under vacuum, and the remaining
solid was dissolved in H2O, which was extracted with DCM (3 × 20
mL). Then, 10 mL of 10% of aqueous HCl was added into the aqueous
phase, and extracted with EtOAc (3 × 20 mL). The combined organic
layer was washed with saturated NaCl solution, dried over Na2SO4, and
concentrated to give the desired product 1 as an oil (0.9 g, 90% yield).
General Procedure for the Synthesis of β,γ-Unsaturated α-
Keto Esters 2a.16 A 100 mL round-bottom flask was charged with a
mixture of pyruvic acid (1.32 g, 15 mmol) and benzaldehyde (1.59 g, 15
mmol) in 5 mL of MeOH, and KOH (1.29 g, 23 mmol) dissolved in 5
mL of methanol, which was dropped to the mixture while maintaining
the temperature at 25 °C. Next, the yellow color of the solution
darkened to orange-red. A voluminous precipitate of yellow potassium
benzylidenepyruvate was accumulated when the temperature rose to 40
°C. The precipitate was filtered using a Buchner funnel and washed with
cold methanol to give potassium 2-oxo-4-phenylbut-3-enoate. The
solid was used in the next step without further purification.
The formed potassium 2-oxo-4-phenylbut-3-enoate (2.68 g, 12.5
mmol) was dissolved in isopropanol (17.5 mL), and then acetyl
chloride (3 mL, 35 mmol) was added dropwise with constant stirring at
0 °C. The reaction mixture was left to react for an additional 2 h at room
temperature. Afterward, the reaction mixture was heated to reflux
overnight until the reaction completed. The excess amount of
isopropanol was removed under reduced pressure. Then 8.5 mL of
H2O was added to the crude mixture, which was extracted with DCM (3
× 25 mL). The combined organic layers were washed with NaHCO3
solution, followed by saturated NaCl aqueous solution (30 mL). The
organic layers were collected, dried over anhydrous MgSO4, and then
concentrated under reduced pressure, to give the final product as a
yellow, viscous oil 2a (2.45 g, 90% yield).
General Procedure for the Synthesis of 2-Oxochromane-3-
carboxylic Acid 4.15 A Schlenk tube was equipped with a stirring bar
and charged with salicyaldehyde (61 mg, 0.5 mmol), malonic acid cyclic
isopropylidene ester (72 mg, 0.5 mmol), diethyl 1,4-dihydro-2,6-
dimethyl-3, and 5-pyridine dicarboxylate (129 mg, 0.5 mmol). 1 mL of
H2O was then added to the mixture. After reacting at room temperature
for 6 h, a saturated aqueous NaHCO3 solution was added to the
reaction until the pH is 8−9. The mixture was extracted with EtOAc (3
× 6 mL); 10% of aqueous HCl was then added to the aqueous layer
until the pH is 3−4. The solution was extracted with EtOAc (3 × 6 mL)
as well. The combined EtOAc was washed with saturated NaCl
solution, dried over Na2SO4, and concentrated to give a white solid of
product 4 (70% yield).
General Procedure for the Catalytic Decarboxylative Aldol
Reaction of 4 and 2. A clean and dried Schlenk tube was charged with
Ni(OAc)2·4H2O (20 mol %), ligand L5 (22 mol %), and 1.0 mL of
mixed solvents (TFEA:EtOH = 9:1). The mixture was stirred
vigorously at room temperature for half an hour. Subsequently, 4
(0.2 mmol, 2 equiv) and 2 (0.1 mmol, 1 equiv) were added, and the
resulting mixture was stirred at a specific temperature for 72 h until the
reaction completed. The reaction mixture was then purified through
flash column chromatography on a silica gel to yield the target products.
General Procedure for Millimole-Scale Catalytic Synthesis of
3i. A clean and dried 100 mL round-bottom flask was charged with
Ni(OAc)2·4H2O (10 mol %), ligand (11 mol %), and 25 mL of EtOH.
The mixture was stirred vigorously at room temperature for 1 h; then 1
(1.3 g, 10 mmol) and 2i (1.26 g, 5 mmol) were added. The resulting
mixture was stirred at 20 °C for 60 h. After completion of reaction
(monitored by TLC), the remaining solvent was removed in vacuum.
The crude product was purified by flash chromatography on silica gel
using hexanes/EtOAc (15:1−5:1) as eluent to give the desired product
3i as a white solid (1.42 g, 84% yield, 96% ee).
General Procedure for the Catalytic Asymmetric Synthesis of
7. A clean and dried Schlenk tube was charged with Ni(OAc)2·4H2O
(20 mol %), ligand L3 (22 mol %), and 1.0 mL of EtOH. The mixture
was stirred vigorously at room temperature for half an hour.
Subsequently, 1 (0.2 mmol, 2 equiv), 6 (0.1 mmol, 1 equiv), and 50
mg of 4A molecular sieves were added, and the resulting mixture was
stirred at 10 °C for 72 h until the reaction completed. The reaction
mixture was then purified through flash column chromatography on a
silica gel to yield the target products 7.
General Procedure for the Catalytic Asymmetric Synthesis of
9. A clean and dried Schlenk tube was charged with Ni(OAc)2·4H2O
(20 mol %), ligand L5 (22 mol %), and 1.0 mL of THF. The mixture
was stirred vigorously at room temperature for half an hour.
Subsequently, 1 (0.2 mmol, 2 equiv) and 8 (0.1 mmol, 1 equiv) were
added, and the resulting mixture was stirred at −10 °C for 72 h until the
reaction completed. The reaction mixture was then purified through
flash column chromatography on a silica gel to yield the target products
9.
Experimental Procedure for the Synthesis of Isopropyl 2-
Hydroxy-4-(naphthalene-2-yl)-2-(2-oxotetrahydrofuran-3-yl)-
butanoate 10. Compound 3d (36 mg, 0.1 mmol, 98% ee) was
dissolved in EtOH and allowed to react in the presence of Pd/C catalyst
(3.6 mg, 10% loading in 50% water) under a hydrogen atmosphere at
ambient temperature for 1 h. The catalyst was removed via filtration
through Celite, followed by removal of the solvent under vacuum. The
crude product was purified via flash chromatography on silica gel using
petroleum ether/EtOAc (15:1−8:1) as eluent, to give the final product
10 as a colorless liquid (33.8 mg, 95%, 94% ee).
Experimental Procedure for the Synthesis of Isopropyl (E)-2-
(4-Chlorostyryl)-2,5-dihydroxy-3-(methyl(phenyl)carbamoyl)-
pentanoate 11.17 To a solution of AlCl3 (73.2 mg, 0.4 mmol, 2 equiv)
in CH2Cl2 (1 mL) was added N-methylaniline (81 μL, 80 mg, 0.75
mmol, 3.75 equiv) slowly at 0 °C. When the solution turned dark, 3i (64
mg, 0.2 mmol, 99% ee) in CH2Cl2 (0.5 mL) was added at 0 °C, and the
mixture was stirred for 5 h at room temperature. To the gray-brown
suspension was added 1 mL of H2O, and the mixture was stirred for 30
min at 0 °C. The mixture was filtered through Celite, and the layers
were separated. The aqueous layer was extracted twice with CH2Cl2,
and the combined organic layers were washed with H2O, saturated
aqueous NaCl, NH4Cl solution, and finally with NaHCO3 (10%). The
combined organic layers were dried over MgSO4, filtered, and
concentrated. The crude product was purified via flash column
chromatography on silica gel using petroleum ether/EtOAc (2:1−
1:1) as eluent and concentrated to give the product 11 as a colorless
liquid (57.1 mg, 64% yield, 99% ee).
General Procedure for the Catalytic Decarboxylative Aldol
Reaction of 1 and 2. A clean and dried Schlenk tube was charged with
Ni(OAc)2·4H2O (20 mol %), ligand L5 (22 mol %), and 1.0 mL of
EtOH. The mixture was stirred vigorously at room temperature for half
an hour. Subsequently, 1 (0.2 mmol, 2 equiv) and 2a (0.1 mmol, 1
equiv) were added, and the resulting mixture was stirred at a
temperature of 10 °C for 72 h until the reaction completed. The
reaction mixture was then purified through flash column chromatog-
raphy on a silica gel to yield the target products.
iso-Propyl-(E)-2-hydroxy-2-(2-oxotetrahydrofuran-3-yl)-4-phen-
ylbut-3-enoate (3a). The compound was prepared according to the
typical procedure, which was purified using petroleum ether/EtOAc
(5:1, v/v) as eluent, obtained (23.7 mg, 78% yield) as a white solid. MP
25
= 90.6.8−92.5 °C, [α]D = +35.2 (c = 0.1 in EtOAc); enantiomeric
excess: 99%. Daicel Chiralpak AS, hexane/iso-propanol = 85/15, flow
rate 1.0 mL/min, 25 °C: tR (major) = 19.305 min, tR (minor) = 12.709
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min; 1H NMR (500 MHz, CDCl3) δ 7.47−7.37 (m, 2H), 7.32 (t, J = 7.6
Hz, 1H), 7.28−7.22 (m, 2H), 6.86 (d, J = 15.9 Hz, 1H), 6.42 (d, J = 15.9
Hz, 1H), 5.14−5.12 (m, 1H), 4.40 (td, J = 8.6, 5.4 Hz, 1H), 4.24 (td, J =
8.4, 7.1 Hz, 1H), 3.95 (s, 1H), 3.13 (dd, J = 9.4, 7.8 Hz, 1H), 2.41−2.23
(m, 2H), 1.31 (dd, J = 6.3, 4.1 Hz, 6H); 13C{1H} NMR (125 MHz,
CDCl3) δ 175.3, 172.2, 136.10, 131.5, 128.5, 128.0, 126.9, 126.9, 77.7,
71.1, 66.7, 46.7, 24.76, 21.6. HRMS (ESI-TOF) m/z: [M + H]+ Calcd
for C17H21O5 305.1384; found: 305.1371.
Methyl-(E)-2-hydroxy-2-(2-oxotetrahydrofuran-3-yl)-4-phenyl-
but-3-enoate (3b). The compound was prepared according to the
typical procedure, which was purified using petroleum ether/EtOAc
(4:1, v/v) as eluent, obtained (21.0 mg, 76% yield) as a colorless liquid;
[α]D25 = +27.4 (c = 0.11 in EtOAc), enantiomeric excess: 99%. Daicel
Chiralpak AS, hexane/iso-propanol = 85/15, flow rate 1.0 mL/min, 25
°C: tR (major) = 24.220 min, tR (minor) = 16.429 min. 1H NMR (500
MHz, CDCl3) δ 7.46−7.38 (m, 2H), 7.36−7.29 (m, 2H), 7.27−7.26
(m, 1H), 6.86 (d, J = 15.9 Hz, 1H), 6.41 (d, J = 15.9 Hz, 1H), 4.40 (td, J
= 8.5, 5.4 Hz, 1H), 4.24 (dt, J = 8.8, 7.6 Hz, 1H), 4.02 (s, 1H), 3.85 (s,
3H), 3.12 (dd, J = 9.4, 8.1 Hz, 1H), 2.50−2.20 (m, 2H); 13C{1H} NMR
(125 MHz, CDCl3) δ 175.5, 173.2, 135.8, 131.6, 128.6, 128.1, 126.9,
126.5, 77.9, 66.8, 53.6, 46.9, 24.8. HRMS (ESI-TOF) m/z:[M + Na]+
Calcd for C15H16O5Na 299.0890; found: 299.0882.
77.8, 71.2, 66.7, 46.6, 24.6, 21.6, 21.6; HRMS (ESI-TOF) m/z: [M +
H]+ Calcd for C17H20FO5 323.1289; found: 323.1302.
iso-Propyl-(E)-4-(3-fluorophenyl)-2-hydroxy-2-(2-oxotetrahydro-
furan-3-yl)but-3-enoate (3f). This compound was prepared according
to the typical procedure, which was purified using petroleum ether/
EtOAc (5:1, v/v) as eluent, obtained (26.5 mg, 82% yield) as a white
25
solid. MP = 89.6−91.1 °C, [α]D = +31.9 (c = 0.1 in EtOAc),
enantiomeric excess: 99%. Daicel Chiralpak AS, hexane/iso-propanol =
85/15, flow rate 1.0 mL/min, 25 °C: tR (major) = 11.077 min, tR
(minor) = 19.346 min. 1H NMR (500 MHz, CDCl3) δ 7.35−7.20 (m,
1H), 7.17 (dt, J = 7.7, 1.2 Hz, 1H), 7.11 (dt, J = 10.1, 2.1 Hz, 1H), 7.02−
6.90 (m, 1H), 6.84 (d, J = 15.8 Hz, 1H), 6.42 (d, J = 15.8 Hz, 1H),
5.15−5.12 (m, 1H), 4.40 (td, J = 8.6, 5.4 Hz, 1H), 4.25 (td, J = 8.4, 6.9
Hz, 1H) 3.96 (s, 1H), 3.13 (dd, J = 9.5, 7.6 Hz, 1H), 2.56−1.98 (m,
2H), 1.32 (dd, J = 6.3, 4.2 Hz, 6H); 13C{1H} NMR (125 MHz, CDCl3)
δ175.1, 172.1, 163.0 (d, J = 245.3 Hz), 138.4 (d, J = 7.8 Hz), 130.4 (d, J
= 2.6 Hz), 130.0 (d, J = 8.3 Hz), 128.3, 122.9 (d, J = 2.7 Hz), 114.8 (d, J
= 21.4 Hz), 113.3 (d, J = 21.8 Hz), 77.6, 71.3, 66.7, 46.6, 24.6, 21.6.
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C17H20FO5 323.1289;
found: 323.1289.
iso-Propyl-(E)-4-(4-fluorophenyl)-2-hydroxy-2-(2-oxotetrahydro-
furan-3-yl)but-3-enoate (3g). This compound was prepared according
to the typical procedure, which was purified using petroleum ether/
EtOAc (5:1, v/v) as eluent, obtained (26.2 mg, 81% yield) as a white
Ethyl-(E)-2-hydroxy-2-(2-oxotetrahydrofuran-3-yl)-4-phenylbut-
3-enoate (3c). This compound was prepared according to the typical
25
solid. MP = 88.0−89.2 °C, [α]D = +32.9 (c = 0.1 in EtOAc),
procedure, which was purified using petroleum ether/EtOAc (4:1, v/v)
25
enantiomeric excess: 99%. Daicel Chiralpak AS, hexane/iso-propanol =
85/15, flow rate 1.0 mL/min, 25 °C: tR (major) = 21.355 min, tR
(minor) = 13.094 min. 1H NMR (500 MHz, CDCl3) δ 7.37 (dd, J = 8.6,
5.5 Hz, 2H), 7.00 (t, J = 8.6 Hz, 2H), 6.82 (d, J = 15.8 Hz, 1H), 6.34 (d, J
= 15.9 Hz, 1H), 5.28−5.02 (m, 1H), 4.50−4.32 (m, 1H), 4.25 (td, J =
8.4, 6.8 Hz, 1H), 3.93 (s, 1H), 3.13 (dd, J = 9.6, 7.6 Hz, 1H), 2.42−2.22
(m, 2H), 1.31 (dd, J = 6.3, 4.0 Hz, 6H); 13C{1H} NMR (125 MHz,
CDCl3) δ 175.2, 172.2, δ 162.5 (d, J = 247.3 Hz), 132.2 (d, J = 3.3 Hz),
130.3, 128.5 (d, J = 8.1 Hz), 126.7 (d, J = 2.3 Hz), 115.5, 115.4, 77.7,
71.2, 66.7, 46.6, 24.6, 21.6. HRMS (ESI-TOF) m/z: [M + H]+ Calcd
for C17H20FO5 323.1289; found: 323.1300.
as eluent, obtained (21.8 mg, 75% yield) as a colorless liquid. [α]D
=
+28.9 (c = 0.12 in EtOAc), enantiomeric excess: 98%. Daicel Chiralpak
AS, hexane/iso-propanol = 85/15, flow rate 1.0 mL/min, 25 °C: tR
(major) = 21.578 min, tR (minor) = 14.063 min. 1H NMR (500 MHz,
CDCl3) δ 7.45−7.38 (m, 2H), 7.35−7.29 (m, 1H), 7.29−7.23 (m, 2H),
6.86 (d, J = 15.9 Hz, 1H), 6.43 (d, J = 15.9 Hz, 1H), 4.40 (td, J = 8.6, 5.4
Hz, 1H), 4.36−4.27 (m, 2H), 4.24 (dt, J = 8.7, 7.4 Hz, 1H), 3.99 (s,
1H), 3.13 (dd, J = 9.4, 7.9 Hz, 1H), 2.54−2.18 (m, 2H), 1.33 (t, J = 7.1
Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 175.4, 172.7, 136.0,
131.5, 128.5, 128.1, 126.94, 126.8, 77.8, 66.8, 62.9, 46.8, 24.7, 14.1.
HRMS (ESI-TOF) m/z [M + H]+ Calcd for C16H19O5 291.1227;
found: 291.1224.
iso-Propyl-(E)-2-hydroxy-4-(naphthalen-2-yl)-2-(2-oxotetrahy-
drofuran-3-yl)but-3-enoate (3d). This compound was prepared
according to the typical procedure, which was purified using petroleum
ether/EtOAc (5:1, v/v) as eluent, obtained (27.3 mg, 77% yield) as a
white solid. MP = 126.0−127.1 °C, [α]D25 = +42.1 (c = 0.1 in EtOAc),
enantiomeric excess: 98%. Daicel Chiralpak AS, hexane/iso-propanol =
85/15, flow rate 1.0 mL/min, 25 °C: tR (major) = 27.805 min, tR
(minor) = 16.296 min. 1H NMR (500 MHz, CDCl3) δ 7.86−7.70 (m,
4H), 7.61 (dd, J = 8.4, 1.8 Hz, 1H), 7.49−7.40 (m, 2H), 7.02 (d, J = 15.9
Hz, 1H), 6.55 (d, J = 15.9 Hz, 1H), 5.17−5.12 (m, 1H), 4.41 (td, J = 8.5,
5.4 Hz, 1H), 4.25 (td, J = 8.3, 7.1 Hz, 1H), 4.00 (s, 1H), 3.17 (dd, J =
9.5, 7.8 Hz, 1H), 2.51−2.17 (m, 2H), 1.32 (dd, J = 6.3, 2.8 Hz, 6H);
13C{1H} NMR (125 MHz, CDCl3) δ 175.4, 172.3, 133.5, 133.5, 133.2,
iso-Propyl-(E)-4-(4-bromophenyl)-2-hydroxy-2-(2-oxotetrahy-
drofuran-3-yl)but-3-enoate (3h). This compound was prepared
according to the typical procedure, which was purified using petroleum
ether/EtOAc (5:1, v/v) as eluent, obtained (31.4 mg, 82% yield) as a
white solid. MP = 134−135.5 °C, [α]D25 = +41.0 (c = 0.1 in EtOAc)
enantiomeric excess: 98%. Daicel Chiralpak AS, hexane/iso-propanol =
85/15, flow rate 1.0 mL/min, 25 °C: tR (major) = 22.992 min, tR
(minor) = 14.100 min. 1H NMR (500 MHz, CDCl3) δ 7.44 (d, J = 8.4
Hz, 2H), 7.30−7.23 (m, 2H), 6.80 (d, J = 15.8 Hz, 1H), 6.41 (d, J = 15.8
Hz, 1H), 5.16−5.11 (m, 1H), 4.51−4.33 (m, 1H), 4.33−4.13 (m, 1H),
3.92 (s, 1H), 3.12 (dd, J = 9.5, 7.6 Hz, 1H), 2.49−2.10 (m, 2H), 1.31 (d,
J = 5.7 Hz, 6H); 13C{1H} NMR (125 MHz, CDCl3) δ 175.1, 172.1,
135.0, 131.6, 130.3, 128.4, 127.7, 121.9, 77.7, 71.3, 66.7, 46.5, 24.6,
21.6. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C17H20BrO5
383.0489; found: 383.0497.
131.6, 128.2, 128.1, 127.6, 127.3, 127.1, 126.3, 126.0, 123.8, 77.8, 71.2,
66.8, 46.7, 24.7, 21.6, 21.6. HRMS (ESI-TOF) m/z: [M + H]+ Calcd
for C21H23O5 355.1540; found: 355.1532.
iso-Propyl-(E)-4-(4-chlorophenyl)-2-hydroxy-2-(2-oxotetrahydro-
furan-3-yl)but-3-enoate (3i). This compound was prepared according
to the typical procedure, which was purified using petroleum ether/
EtOAc (5:1, v/v) as eluent, obtained (27.8 mg, 82% yield) as a white
iso-Propyl-(E)-4-(2-fluorophenyl)-2-hydroxy-2-(2-oxotetrahydro-
furan-3-yl)but-3-enoate (3e). This compound was prepared according
to the typical procedure, which was purified using petroleum ether/
EtOAc (5:1, v/v) as eluent, obtained (26.7 mg, 83% yield) as a white
25
solid. MP = 139.6−141.5 °C, [α]D = +32.4 (c = 0.1 in EtOAc),
enantiomeric excess: 99%. Daicel Chiralpak AS, hexane/iso-propanol =
85/15, flow rate 1.0 mL/min, 25 °C: tR (major) = 21.083 min, tR
(minor) = 13.688 min. 1H NMR (500 MHz, CDCl3) δ 7.33 (d, J = 8.3
Hz, 2H), 7.28 (d, J = 8.3 Hz, 2H), 6.81 (d, J = 15.9 Hz, 1H), 6.40 (d, J =
15.8 Hz, 1H), 5.16−5.11 (m, 1H), 4.40 (td, J = 8.6, 5.4 Hz, 1H), 4.27-
4.24 (m, 1H), 3.95 (s, 1H), 3.13 (dd, J = 9.5, 7.6 Hz, 1H), 2.37−2.26
(m, 2H), 1.31 (t, J = 5.6 Hz, 6H); 13C{1H} NMR (125 MHz, CDCl3) δ
175.2, 172.1, 134.6, 133.7, 130.3, 128.7, 128.1, 127.6, 77.7, 71.3, 66.7,
46.6, 24.6, 21.6. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C17H20ClO5 361.0813; found: 361.0824.
25
solid. MP = 86.8−88.2 °C, [α]D = +30.8 (c = 0.1 in EtOAc),
enantiomeric excess: 99%. Daicel Chiralpak AS, hexane/iso-propanol =
85/15, flow rate 1.0 mL/min, 25 °C: tR (major) = 16.467 min, tR
(minor) = 12.147 min. 1H NMR (500 MHz, CDCl3) δ 7.48 (td, J = 7.7,
1.8 Hz, 1H), 7.22 (dd, J = 8.5, 1.7 Hz, 1H), 7.10 (td, J = 7.5, 1.2 Hz,
1H), 7.03 (d, J = 11.0, 8.3, 1.2 Hz, 1H), 6.98 (d, J = 16.1 Hz, 1H), δ 6.55
(d, J = 16.1 Hz, 1H), 5.15−5.13 (m, 1H), 4.40 (td, J = 8.6, 5.5 Hz, 1H),
4.25 (td, J = 8.3, 7.0 Hz, 1H), 3.95 (s, 1H), 3.15 (dd, J = 9.5, 7.7 Hz,
1H), 2.53−2.21 (m, 2H), 1.32 (dd, J = 6.3, 3.4 Hz, 6H); 13C{1H} NMR
(125 MHz, CDCl3) δ 175.2, 172.1, 160.4 (d, J = 250.1 Hz), 129.7 (d, J =
5.5 Hz), 129.3 (d, J = 8.3 Hz), 128.2 (d, J = 3.2 Hz), 124.2 (d, J = 3.2
Hz), 124.1 (d, J = 3.6 Hz), 123.9 (d, J = 12.0 Hz), 115.7 (d, J = 22.1 Hz),
iso-Propyl-(E)-4-(2,6-dichlorophenyl)-2-hydroxy-2-(2-oxotetra-
hydrofuran-3-yl)but-3-enoate (3j). This compound was prepared
according to the typical procedure, which was purified using petroleum
ether/EtOAc (5:1) as eluent, obtained (30.2 mg, 81% yield) as a white
4830
https://dx.doi.org/10.1021/acs.joc.0c02854
J. Org. Chem. 2021, 86, 4825−4834

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
25
solid. MP = 142−143.1 °C, [α]D = +34.0 (c = 0.1 in EtOAc),
151.1, 136.0, 131.8, 128.6, 128.3, 128.2, 127.9, 126.8, 126.7, 124.5,
122.5, 116.6, 77.1, 70.8, 48.9, 26.9, 21.7, 21.6. HRMS (ESI): HRMS
(ESI-TOF) m/z: [M + H]+ Calcd for C22H23O5 367.1540; found:
367.1542.
enantiomeric excess: 98%. Daicel Chiralpak AS, hexane/iso-propanol =
85/15, flow rate 1.0 mL/min, 25 °C: tR (major) = 12.418 min, tR
(minor) = 10.922 min. 1H NMR (500 MHz, CDCl3) δ 7.31 (d, J = 8.0
Hz, 2H), 7.10 (t, J = 8.0 Hz, 1H), 6.90 (d, J = 16.2 Hz, 1H), 6.47 (d, J =
16.2 Hz, 1H), 5.19−5.14 (m, 1H), 4.42 (td, J = 8.4, 5.4 Hz, 1H), 4.28−
4.24 (m, 1H), 3.14 (t, J = 8.8 Hz, 1H), 2.43−2.31 (m, 2H), 1.32 (dd, J =
6.2, 2.6 Hz, 6H); 13C{1H} NMR (125 MHz, CDCl3) δ 175.2, 171.9,
135.3, 134.5, 133.7, 128.5, 128.4, 128.4, 125.5, 77.6, 71.2, 66.7, 46.6,
24.7, 21.6. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C17H19Cl2O5
373.0604; found: 373.0605.
iso-Propyl-(E)-4-(4-fluorophenyl)-2-hydroxy-2-(2-oxochroman-3-
yl)but-3-enoate (5b). This compound was prepared according to the
typical procedure, which was purified using petroleum ether/EtOAc
(15:1, v/v) as eluent, obtained (30.7 mg, 80% yield) as a colorless
liquid. [α]D25 = +26.0 (c = 0.12 in EtOAc), enantiomeric excess: 92%.
Daicel Chiralpak AS, hexane/iso-propanol = 95/5, flow rate 1.0 mL/
1
min, 25 °C: tR (major) = 20.407 min, tR (minor) = 15.720 min. H
iso-Propyl-(E)-2-hydroxy-2-(2-oxotetrahydrofuran-3-yl)-4-(p-
tolyl)but-3-enoate (3k). This compound was prepared according to
the typical procedure, which was purified using petroleum ether/EtOAc
(5:1) as eluent, obtained (25.2 mg, 79% yield) as a white solid. MP =
NMR (500 MHz, CDCl3) δ 7.37 (m, 2H), 7.29−7.21 (m, 1H), 7.17 (d,
J = 7.5 Hz, 1H), 7.11−7.08 (m, 3H), 7.07−6.98 (m, 1H), 6.89 (dd, J =
16.0, 3.0 Hz, 1H), 6.30 (d, J = 15.9 Hz, 1H), 5.19−5.15 (m, 1H), 3.91
(s, 1H), 3.39 (dd, J = 15.5, 12.7 Hz, 1H), 3.19 (dd, J = 12.6, 6.1 Hz, 1H),
3.04 (dd, J = 15.5, 6.1 Hz, 1H), 1.33 (d, J = 6.2 Hz, 6H); 13C{1H} NMR
(125 MHz, CDCl3) δ 172.1, 168.2, 151.1, 132.2, 130.6, 128.5, 128.4,
127.9, 126.5, 124.6, 122.4, 116.6, 115.7, 115.5, 77.2 70.9, 48.8, 26.8,
21.7, 21.6. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H22FO5
385.1446; found: 385.1441.
25
109.3−111.2 °C, [α]D = +37.6 (c = 0.1 in EtOAc), enantiomeric
excess: 98%. Daicel Chiralpak AS, hexane/iso-propanol = 85/15, flow
rate 1.0 m/min, 25 °C: tR (major) = 16.798 min, tR (minor) = 12.242
min; 1H NMR (500 MHz, CDCl3) δ 7.30 (d, J = 8.1 Hz, 2H), 7.12 (d, J
= 7.9 Hz, 2H), 6.81 (d, J = 15.9 Hz, 1H), 6.37 (d, J = 15.8 Hz, 1H),
5.15−5.10 (m, 1H), 4.39 (td, J = 8.5, 5.4 Hz, 1H), 4.28−4.19 (m, 1H),
3.93 (s, 1H), 3.12 (dd, J = 9.4, 7.9 Hz, 1H), 2.38−2.35 (m, 1H), 2.34 (s,
3H) 2.32−2.24 (m, 1H), 1.31 (dd, J = 6.3, 4.6 Hz, 6H); 13C{1H} NMR
(125 MHz, CDCl3) δ 175.4, 172.3, 137.9, 133.3, 131.3, 129.2, 126.8,
125.8, 77.7, 71.0, 66.7, 46.7, 24.8, 21.6, 21.2. HRMS (ESI-TOF) m/z:
[M + Na]+ Calcd for C18H22O5Na 341.1359; found: 341.1363.
iso-Propyl-(E)-4-(3,4-dimethylphenyl)-2-hydroxy-2-(2-oxotetra-
hydrofuran-3-yl)but-3-enoate (3l). This compound was prepared
according to the typical procedure, which was purified using petroleum
ether/EtOAc (5:1, v/v) as eluent, obtained (23.6 mg,71% yield) as a
white solid. MP = 113.8−113.9 °C, [α]D25 = +35.4 (c = 0.1 in EtOAc),
enantiomeric excess: 98%. Daicel Chiralpak AS, hexane/iso-propanol =
85/15, flow rate 1.0 mL/min, 25 °C: tR (major) = 13.479 min, tR
(minor) = 10.328 min. 1H NMR (500 MHz, CDCl3) δ 7.19 (d, J = 1.8
Hz, 1H), 7.14 (dd, J = 7.7, 1.9 Hz, 1H), 7.07 (d, J = 7.8 Hz, 1H), 6.78 (d,
J = 15.8 Hz, 1H), 6.36 (d, J = 15.9 Hz, 1H), 5.15−5.10 (m, 1H), 4.39
(td, J = 8.5, 5.4 Hz, 1H), 4.28−4.19 (m, 1H), 3.91 (s, 1H), 3.12 (dd, J =
9.4, 8.0 Hz, 1H), 2.42−2.28 (m, 2H), 2.25 (d, J = 4.1 Hz, 6H), 1.31 (dd,
J = 6.3, 4.0 Hz, 6H); 13C{1H} NMR (125 MHz, CDCl3) δ 175.4, 172.3,
136.6, 136.6, 133.7, 131.4, 129.8, 128.0, 125.7, 124.4, 77.7, 71.0, 66.7,
46.8, 24.8, 21.6, 21.6, 19.7, 19.5. HRMS (ESI-TOF) m/z: [M + H]+
Calcd for C19H25O5 333.1697; found: 333.1693.
iso-Propyl-(E)-4-(4-bromophenyl)-2-hydroxy-2-(2-oxochroman-
3-yl)but-3-enoate (5c). This compound was prepared according to the
typical procedure, which was purified using petroleum ether/EtOAc
(15:1, v/v) as eluent, obtained (36.1 mg, 81% yield) as a colorless
liquid. [α]D25 = +29.5 (c = 0.1 in EtOAc), enantiomeric excess: 94%.
Daicel Chiralpak AS, hexane/iso-propanol = 95/5, flow rate 1.0 mL/
1
min, 25 °C: tR (major) = 19.537 min, tR (minor) = 15.728 min. H
NMR (500 MHz, CDCl3) δ 7.54−7.39 (m, 2H), 7.27−7.25 (m, 3H),
7.16 (d, J = 7.4 Hz, 1H), 7.09 (td, J = 7.5, 1.2 Hz, 1H), 7.05 (d, J = 8.1
Hz, 1H), 6.87 (d, J = 15.9 Hz, 1H), 6.38 (d, J = 15.8 Hz, 1H), 5.20−5.15
(m, 1H), 3.91 (s, 1H), 3.39 (dd, J = 15.4, 12.7 Hz, 1H), 3.19 (dd, J =
12.6, 6.1 Hz, 1H), 3.03 (dd, J = 15.5, 6.1 Hz, 1H), 1.33 (dd, J = 6.3, 1.8
Hz, 6H); 13C{1H} NMR (125 MHz, CDCl3) δ 172.0, 168.1, 151.1,
134.9, 131.7, 130.6, 128.3, 127.9, 127.5, 124.6, 122.3, 122.0, 116.6, 77.2,
71.0, 48.7, 26.7, 21.6, 21.6. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd
for C22H21BrO5Na 467.0465; found: 467.0451.
iso-Propyl-(E)-4-(4-chlorophenyl)-2-hydroxy-(2-oxochroman-3-
yl)but-3-enoate (5d). This compound was prepared according to the
typical procedure, which was purified using petroleum ether/EtOAc
(15:1, v/v) as eluent, obtained (33.3 mg, 83% yield) as a colorless
liquid. [α]D25 = +24.2 (c = 0.11 in EtOAc), enantiomeric excess: 93%.
Daicel Chiralpak AS, hexane/iso-propanol = 95/5, flow rate 1.0 mL/
iso-Propyl-(E)-2-hydroxy-4-(4-methoxyphenyl)-2-(2-oxotetrahy-
drofuran-3-yl)but-3-enoate (3m). This compound was prepared
according to the typical procedure, which was purified using petroleum
ether/EtOAc (5:1, v/v) as eluent, obtained (25.7 mg, 77% yield) as a
white solid. MP = 107.3−109.2 °C, [α]D25 = +34.2 (c = 0.1 in EtOAc),
enantiomeric excess: 98%. Daicel Chiralpak AS, hexane/iso-propanol =
95/5, flow rate 1.0 mL/min, 25 °C: tR (major) = 30.843 min, tR (minor)
= 24.951 min; 1H NMR (500 MHz, CDCl3) δ 7.34 (d, J = 8.7 Hz, 2H),
6.85 (d, J = 8.7 Hz, 2H), 6.78 (d, J = 15.9 Hz, 1H), 6.29 (d, J = 15.9 Hz,
1H), 5.17−5.06 (m, 1H), 4.39 (td, J = 8.6, 5.4 Hz, 1H), 4.28−4.18 (m,
1H), 3.92 (s, 1H), 3.80 (s, 3H), 3.12 (dd, J = 9.4, 7.8 Hz, 1H), 2.39−
2.25 (m, 2H), 1.31 (dd, J = 6.3, 3.5 Hz, 6H); 13C{1H} NMR (125 MHz,
CDCl3) δ δ 175.4, 172.4, 159.6, 130.9, 128.9, 128.2, 124.7, 114.0, 77.8,
71.0, 66.7, 55.3, 46.8, 24.8, 21.7, 21.6. HRMS (ESI-TOF) m/z: [M +
H]+ Calcd for C18H23O6 335.1489; found: 335.1485.
1
min, 25 °C: tR (major) = 20.345 min, tR (minor) = 15.018 min. H
NMR (500 MHz, CDCl3) δ 7.35−7.28 (m, 4H), 7.28−7.23 (m, 1H),
7.19−7.14 (m, 1H), 7.09 (td, J = 7.5, 1.2 Hz, 1H), 7.05 (dd, J = 8.2, 1.1
Hz, 1H), 6.88 (d, J = 15.9 Hz, 1H), 6.36 (d, J = 15.8 Hz, 1H), 5.19−5.16
(m, 1H), 3.91 (s, 1H), 3.39 (dd, J = 15.5, 12.6 Hz, 1H), 3.19 (dd, J =
12.6, 6.1 Hz, 1H), 3.03 (dd, J = 15.5, 6.1 Hz, 1H), 1.33 (dd, J = 6.3, 1.5
Hz, 6H); 13C{1H} NMR (125 MHz, CDCl3) δ 172.0, 168.1, 151.1,
134.5, 133.8, 130.6, 128.8, 128.3, 128.0, 127.9, 127.4, 124.6, 122.3,
116.6, 77.2, 71.0, 48.8, 26.7, 21.6, 21.6. HRMS (ESI-TOF) m/z: [M +
H]+ Calcd for C22H22ClO5 401.1150; found: 401.1164.
iso-Propyl-(E)-2-hydroxy-2-(2-oxochroman-3-yl)-4-(p-tolyl)but-
3-enoate (5e). This compound was prepared according to the typical
procedure, which was purified using petroleum ether/EtOAc (15:1, v/
25
v) as eluent, obtained (29.3 mg, 77% yield) as a colorless liquid. [α]D
= +24.5 (c = 0.1 in EtOAc), enantiomeric excess: 95%. Daicel Chiralpak
AS, hexane/iso-propanol = 85/15, flow rate 1.0 mL/min, 25 °C: tR
(major) = 17.772 min, tR (minor) = 13.253 min. 1H NMR (500 MHz,
CDCl3) δ 7.31 (d, J = 7.8 Hz, 2H), 7.26 (d, J = 5.3 Hz, 1H), 7.17−7.14
(m, 3H), 7.09 (t, J = 7.4 Hz, 1H), 7.05 (d, J = 8.1 Hz, 1H), 6.89 (d, J =
15.9 Hz, 1H), 6.33 (d, J = 15.8 Hz, 1H), 5.20−5.15 (m, 1H), 3.93 (s,
1H), 3.42 (dd, J = 15.3, 13.1 Hz, 1H), 3.17 (dd, J = 13.0, 6.1 Hz, 1H),
3.05 (dd, J = 15.4, 6.1 Hz, 1H), 2.35 (s, 3H), 1.32 (dd, J = 6.3, 3.3 Hz,
6H); 13C{1H} NMR (125 MHz, CDCl3) δ 172.2, 168.5, 151.1, 138.1,
133.2, 131.6, 129.3, 128.6, 128.3, 127.9, 126.7, 126.5, 125.6, 124.5,
122.5, 116.5, 77.1, 70.7, 49.0, 26.9, 21.7, 21.6, 21.2. HRMS (ESI):
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H25O5 381.1697;
found: 381.1696.
iso-Propyl-(E)-2-hydroxy-2-(2-oxochroman-3-yl)-4-phenylbut-3-
enoate (5a). This compound was prepared according to the typical
procedure, which was purified using petroleum ether/EtOAc (15:1, v/
25
v) as eluent, obtained (28.9 mg, 79% yield) as a colorless liquid. [α]D
= +21.7 (c = 0.11 in EtOAc), enantiomeric excess: 98%. Daicel
Chiralpak AS, hexane/iso-propanol = 95/5, flow rate 1.0 mL/min, 25
°C: tR (major) = 20.555 min, tR (minor) = 14.958 min. 1H NMR (500
MHz, CDCl3) δ 7.41 (d, J = 7.7 Hz, 2H), 7.34 (dd, J = 8.4, 6.7 Hz, 2H),
7.30−7.22 (m, 2H), 7.16 (d, J = 7.5 Hz, 1H), 7.09 (td, J = 7.5, 1.3 Hz,
1H), 7.07−7.02 (m, 1H), 6.93 (d, J = 15.8 Hz, 1H), 6.39 (d, J = 15.8 Hz,
1H), 5.19−5.16 (m, 1H), 3.93 (s, 1H), 3.41 (dd, J = 15.4, 12.9 Hz, 1H),
3.18 (dd, J = 12.9, 6.1 Hz, 1H), 3.05 (dd, J = 15.4, 6.1 Hz, 1H), 1.33 (dd,
J = 6.3, 2.3 Hz, 6H); 13C{1H} NMR (125 MHz, CDCl3) δ 172.2, 168.4,
4831
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The Journal of Organic Chemistry
pubs.acs.org/joc
Note
iso-Propyl-(E)-2-hydroxy-4(4-methoxyphenyl)-2-(2-oxochro-
man-3-yl)but-3-enoate (5f). This compound was prepared according
to the typical procedure, which was purified using petroleum ether/
EtOAc (15:1, v/v) as eluent, obtained (23.4 mg, 59% yield) as a
colorless liquid. [α]D25 = +24.0 (c = 0.1 in EtOAc), enantiomeric excess:
93%. Daicel Chiralpak AS, hexane/iso-propanol = 85/15, flow rate 1.0
mL/min, 25 °C: tR (major) = 30.448 min, tR (minor) = 36.755 min. 1H
NMR (500 MHz, CDCl3) δ 7.39−7.31 (m, 2H), 7.28−7.21 (m, 1H),
7.16 (d, J = 7.4 Hz, 1H), 7.09 (t, J = 7.4 Hz, 1H), 7.05−7.04 (m, 1H),
6.90−6.82 (m, 3H), 6.24 (d, J = 15.8 Hz, 1H), 5.17 (m, 1H), 3.92 (s,
1H), 3.82 (s, 3H), 3.50−3.36 (m, 1H), 3.16 (dd, J = 12.9, 6.1 Hz, 1H),
3.06 (d, J = 15.5, 6.1 Hz, 1H), 1.33 (dd, J = 6.3, 3.4 Hz, 6H); 13C{1H}
NMR (125 MHz, CDCl3) δ 172.3, 168.5, 159.6, 151.1, 131.2, 128.7,
128.3, 128.1, 127.9, 124.5, 124.3, 122.5, 116.5, 114.0, 77.1, 70.7, 55.3,
49.0, 29.7, 26.9, 21.7, 21.6. HRMS (ESI): HRMS (ESI-TOF) m/z: [M
+ H]+ Calcd for C23H25O6 397.1646; found: 397.1653.
Daicel Chiralpak AS, hexane/iso-propanol = 95/5, flow rate 1.0 mL/
min, 25 °C: tR (major) = 28.661 min, tR (minor) = 18.116 min. H
1
NMR (500 MHz, CDCl3) δ 7.46−7.38 (m, 2H), 7.37−7.31 (m, 2H),
7.30−7.27 (m, 1H), 7.05 (d, J = 8.4 Hz, 1H), 6.92 (d, J = 15.9 Hz, 1H),
6.64 (dd, J = 8.4, 2.6 Hz, 1H), 6.60 (d, J = 2.5 Hz, 1H), 6.37 (d, J = 15.8
Hz, 1H), 5.20−5.15 (m, 1H), 3.92 (s, 1H), 3.78 (s, 3H), 3.33 (ddd, J =
15.2, 12.9, 1.1 Hz, 1H), 3.16 (dd, J = 12.8, 6.1 Hz, 1H), 2.99 (dd, J =
15.2, 6.1 Hz, 1H), 1.32 (dd, J = 6.3, 2.7 Hz, 6H); 13C{1H} NMR (125
MHz, CDCl3) δ 172.2, 168.3, 159.7, 151.8, 136.0, 131.7, 128.6, 128.4,
128.1, 126.8, 126.7, 114.1, 110.6, 102.2, 77.1, 70.8, 55.5, 49.2, 26.2,
21.7, 21,6. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H25O6
397.1646; found: 397.1647.
3-Hydroxy(4-nitrophenyl)methyl)dihydrofuran-2-(3H)-one (7).
This compound was prepared according to the typical procedure,
which was purified using petroleum ether/EtOAc (3:1, v/v) as eluent,
obtained (12.4 mg, 52% yield) as a yellow solid. MP = 139.8−141.6 °C,
[α]D25 = +17.9 (c = 0.1 in EtOAc), enantiomeric excess: 93%. Daicel
Chiralpak AS-H, hexane/iso-propanol = 80/20, flow rate 1.0 mL/min,
iso-Propyl-(E)-4-(3,4-dimethylphenyl)-2-hydroxy-2-(2-oxochro-
man-3-yl)but-3-enoate (5g). This compound was prepared according
to the typical procedure, which was purified using petroleum ether/
EtOAc (15:1, v/v) as eluent, obtained (29.2 mg, 74% yield) as a
colorless liquid. [α]D25 = +20.7 (c = 0.1 in EtOAc), enantiomeric excess:
93%. Daicel Chiralpak AS, hexane/iso-propanol = 95/5, flow rate 1.0
mL/min, 25 °C: tR (major) = 17.323 min, tR (minor) = 11.383 min. 1H
NMR (500 MHz, CDCl3) δ 7.30−7.22 (m, 1H), 7.22−7.12 (m, 3H),
7.12−7.06 (m, 2H), 7.04 (dd, J = 8.1, 1.1 Hz, 1H), 6.86 (d, J = 15.8 Hz,
1H), 6.31 (d, J = 15.9 Hz, 1H), 5.18−5.16 (m, 1H), 3.92 (s, 1H), 3.42
(dd, J = 15.4, 13.1 Hz, 1H), 3.16 (dd, J = 13.0, 6.1 Hz, 1H), 3.05 (dd, J =
15.5, 6.1 Hz, 1H), 2.26 (d, J = 4.9 Hz, 6H), 1.32 (dd, J = 6.3, 4.8 Hz,
6H); 13C{1H} NMR (125 MHz, CDCl3) δ 172.3, 168.5, 151.1, 136.8,
136.8, 133.6, 131.8, 129.9, 128.3, 128.0, 127.9, 125.4, 124.5, 124.4,
122.6, 116.5, 77.0, 70.7, 49.1, 26.9, 21.7, 21.6, 19.7, 19.5. HRMS (ESI-
TOF) m/z: [M + H]+ Calcd for C24H27O5 395.1853; found: 395.1858.
iso-Propyl-(E)-2-hydroxy-2-(6-methyl-2-oxochroman-3-yl)-4-
phenylbut-3-enoate(5h). This compound was prepared according to
the typical procedure, which was purified using petroleum ether/EtOAc
(15:1, v/v) as eluent, obtained (30.5 mg, 80% yield) as a colorless
liquid. [α]D25 = +29.1 (c = 0.1 in EtOAc), enantiomeric excess: 95%.
Daicel Chiralpak AS, hexane/iso-propanol = 85/15, flow rate 1.0 mL/
1
25 °C: tR (major) = 14.462 min, tR (minor) = 21.597 min. H NMR
(500 MHz, CDCl3) δ 8.25 (d, J = 8.8 Hz, 2H), 7.60 (d, J = 8.7 Hz, 2H),
4.97 (d, J = 8.7 Hz, 1H), 4.52 (s, 1H), 4.39−4.35 (m, 1H), 4.22−4.06
(m, 1H), 2.88 (dt, J = 11.5, 8.9 Hz, 1H), 2.17−1.92 (m, 2H); 13C{1H}
NMR (125 MHz, CDCl3) δ 178.4, 147.9, 147.4, 127.4, 123.9, 73.7,
67.0, 46.1, 25.7. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C11H12NO5 238.0710; found: 238.0709.
3-Hydroxy-3-(2-oxotetrahydrofuran-3-yl)indolin-2-one (9). This
compound was prepared according to the typical procedure, which was
purified using DCM/EtOAc (3:1, v/v) as eluent, obtained (20.4 mg, 87
yield) as an off-white solid, enantiomeric excess: 96%. Daicel Chiralpak
AD-H, hexane/iso-propanol = 90/10, flow rate 1.0 mL/min, 25 °C: tR
(major) = 25.897 min, tR (minor) = 21.243 min. 1H NMR (500 MHz,
Acetone-d6) δ 9.46 (s, 1H), 7.53 (dd, J = 7.5, 1.1 Hz, 1H), 7.27 (td, J =
7.7, 1.3 Hz, 1H), 7.01 (td, J = 7.6, 1.0 Hz, 1H), 6.92 (d, J = 7.9 Hz, 1H),
5.44 (s, 1H), 4.36 (td, J = 8.7, 3.8 Hz, 1H), 4.27 (td, J = 8.8, 7.6 Hz, 1H),
3.42 (t, J = 9.8 Hz, 1H), 2.51−2.34 (m, 2H); 13C{1H} NMR (125 MHz,
Acetone-d6) δ178.1, 176.7, 143.5, 130.8, 129.9, 125.7, 122.9, 110.9,
76.2, 67.4, 46.2, 24.6. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C11H12NO5 234.0761; found: 234.0763.
1
min, 25 °C: tR (major) = 23.600 min, tR (minor) = 13.961 min. H
iso-Propyl-2-hydroxy-4-(naphthalen-2-yl)-2-(2-oxotetrahydro-
furan-3-yl)butanoate (10). This compound was prepared according to
the typical procedure, which was purified using petroleum ether/EtOAc
(10:1, v/v) as eluent, obtained (33.8 mg, 95% yield) as a colorless
liquid. [α]D25 = +38.2 (c = 0.12 in EtOAc), enantiomeric excess: 94%.
Daicel Chiralpak OD, hexane/iso-propanol = 90/10, flow rate 1.0 mL/
NMR (500 MH, CDCl3) δ 7.45−7.38 (m, 2H), 7.36−7.30 (m, 2H),
7.31−7.23 (m, 1H), 7.03 (dd, J = 8.4, 2.0 Hz, 1H), 6.95 (dd, J = 11.8,
2.0 Hz, 2H), 6.91 (d, J = 5.7 Hz, 1H), 6.38 (d, J = 15.9 Hz, 1H), 5.18−
5.16 (m, 1H), 3.95 (s, 1H), 3.45−3.30 (m, 1H), 3.16 (dd, J = 12.9, 6.1
Hz, 1H), 3.00 (dd, J = 15.5, 6.1 Hz, 1H), 2.29 (s, 3H), 1.32 (dd, J = 6.2,
1.8 Hz, 6H); 13C{1H} NMR (125 MHz, CDCl3) δ 172.2, 168.6, 149.0,
136.0, 134.2, 131.7, 128.7, 128.6, 128.4, 128.1, 126.8, 126.8, 122.1,
116.2, 77.2, 70.7, 49.1, 26.8, 21.7, 21.6, 20.7. HRMS (ESI-TOF) m/z:
[M + H]+ Calcd for C23H25O5 381.1697; found: 381.1698.
1
min, 25 °C: tR (major) = 19.05 min, tR (minor) = 18 min. H NMR
(500 MHz, CDCl3) δ 7.85−7.72 (m, 3H), 7.61 (d, J = 1.7 Hz, 1H),
7.45−7.41 (m, 2H), 7.32 (dd, J = 8.3, 1.8 Hz, 1H), 5.11−5.09 (m, 1H),
4.38 (td, J = 8.4, 5.2 Hz, 1H), 4.26−4.17 (m, 1H), 3.86 (s, 1H), 3.03−
2.89 (m, 2H), 2.74−2.70 (m, 1H), 2.64−2.53 (m, 1H), 2.30−2.17 (m,
3H), 1.31 (dd, J = 6.3, 4.3 Hz, 6H); 13C{1H} NMR (125 MHz, CDCl3)
δ 175.9, 173.5, 138.5, 133.5, 132.0, 128.0, 127.6, 127.4, 127.1, 126.4,
125.9, 125.2, 77.5, 70.7, 66.6, 46.0, 37.8, 30.1, 24.7, 21.7, 21.7. HRMS
(ESI-TOF) m/z: [M + H]+ Calcd for C21H25O5 357.1697; found:
357.1709.
iso-Propyl-(E)-2-hydroxy-2-(8-methoxy-2-oxochroman-3-yl)-4-
phenylbut-3-enoate (5i). This compound was prepared according to
the typical procedure, which was purified using PE (petroleum ether)/
EtOAc (15:1, v/v) as eluent, obtained (26.5 mg, 67% yield) as a
colorless liquid. [α]D25 = +27.7 (c = 0.1 in EtOAc), enantiomeric excess:
74%. Daicel Chiralpak OD, hexane/iso-propanol = 95/5, flow rate 1.0
mL/min, 25 °C: tR (major) = 30.363 min, tR (minor) = 23.653 min. 1H
NMR (500 MHz, CDCl3) δ 7.40 (d, J = 7.3 Hz, 2H), 7.35 (dd, J = 8.2,
6.8 Hz, 2H), 7.30−7.25 (m, 1H), 7.04 (t, J = 7.9 Hz, 1H), 6.93 (d, J =
15.8 Hz, 1H), 6.85 (d, J = 8.2 Hz, 1H), 6.74 (d, J = 7.6 Hz, 1H), 6.38 (d,
J = 15.9 Hz, 1H), 5.20−5.15 (m, 1H), 3.95 (s, 1H), 3.88 (s, 3H), 3.53−
3.36 (m, 1H), 3.16 (dd, J = 13.3, 6.0 Hz, 1H), 3.04 (dd, J = 15.5, 6.0 Hz,
1H), 1.32 (dd, J = 6.2, 3.6 Hz, 6H); 13C{1H} NMR (125 MHz, CDCl3)
δ 172.1, 167.8, 147.5, 140.4, 136.1, 131.8, 128.6, 128.2, 126.9, 126.8,
124.5, 123.8, 119.4, 111.2,77.1 70.7, 56.1, 49.0, 27.1, 21.7, 21.6. HRMS
(ESI-TOF) m/z: [M + H]+ Calcd for C23H25O6 397.1646; found:
397.1643.
iso-Propyl-(E)-2,5-dihydroxy-3-(methyl(phenyl)carbamoyl)-2-
styrylpentanoate (11). This compound was prepared according to the
typical procedure, which was purified using petroleum ether/EtOAc
(2:1, v/v) as eluent, obtained (57.1 mg; 64 yield) as a colorless liquid.
[α]D25 = +28.1 (c = 0.1 in EtOAc), enantiomeric excess: 99%. Daicel
Chiralpak AS, hexane/iso-propanol = 80/20, flow rate 1.0 mL/min, 25
1
°C: tR (major) = 6.548 min, tR (minor) = 5.040 min. H NMR (500
MHz, Acetone-d6) δ 7.53−7.46 (m, 4H), 7.45−7.37 (m, 3H), 7.35−
7.25 (m, 2H), 6.75 (d, J = 15.8 Hz, 1H), 6.31 (d, J = 15.8 Hz, 1H), 5.15
(s, 1H), 4.96−4.90 (m, 1H), 3.51−3.64 (m, 2H), 3.45 (s, 1H), δ 3.24
(dd, J = 10.4, 3.5 Hz, 1H), 3.14 (s, 3H), 2.21−2.10 (m, 1H), 1.71−1.60
(m, 1H), 1.17 (d, J = 6.3 Hz, 6H); 13C{1H} NMR (126 MHz, CDCl3) δ
173.9, 171.4, 143.0, 134.5, 133.6, 130.1, 129.7, 129.4, 128.8, 128.3,
127.9, 127.49, 79.2, 69.9, 60.4, 45.6, 37.7, 32.2, 21.6, 21.4. HRMS (ESI-
TOF) m/z: [M + Na]+ Calcd for C24H28ClNO5Na 468.1548; found:
468.1563.
iso-Propyl-(E)-2-hydroxy-2-(7-methoxy-2-oxochroman-3-yl)-4-
phenylbut-3-enoate (5j). This compound was prepared according to
the typical procedure, which was purified using petroleum ether/EtOAc
(15:1, v/v) as eluent, obtained (29.8 mg, 75% yield) as a colorless
liquid. [α]D25 = +31.1 (c = 0.1 in EtOAc), enantiomeric excess: 95%.
4832
https://dx.doi.org/10.1021/acs.joc.0c02854
J. Org. Chem. 2021, 86, 4825−4834

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
Med. Chem. 2016, 24, 5823−5833. (e) Nascimento de Oliveira, M.;
Fournier, J.; Arseniyadis, S.; Cossy, J. A Palladium-Catalyzed
Asymmetric Allylic Alkylation Approach to α-Quaternary γ-Butyr-
olactones. Org. Lett. 2017, 19 (1), 14−17.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02854.
■
sı
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NMR and HPLC spectra, and crystallographic data for 3h
(PDF)
Accession Codes
CCDC 2035137 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_
request@ccdc.cam.ac.uk, or by contacting The Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge
CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Authors
■
Xingen Hu − College of Chemistry and Materials Engineering,
Wenzhou University, Wenzhou 325035, China;
Email: hxgwzu@126.com
Jun Jiang − College of Chemistry and Materials Engineering,
Wenzhou University, Wenzhou 325035, China; orcid.org/
0000-0001-5815-1600; Email: junjiang@wzu.edu.cn
Authors
Lingchen He − College of Chemistry and Materials Engineering,
Wenzhou University, Wenzhou 325035, China
Ebrahim-Alkhalil M. A. Ahmed − College of Chemistry and
Materials Engineering, Wenzhou University, Wenzhou
325035, China; orcid.org/0000-0002-8658-8110
Hongxin Liu − College of Chemistry and Materials Engineering,
Wenzhou University, Wenzhou 325035, China; orcid.org/
0000-0001-5401-2953
Hong-ping Xiao − College of Chemistry and Materials
Engineering, Wenzhou University, Wenzhou 325035, China
Juan Li − College of Chemistry and Materials Engineering,
Wenzhou University, Wenzhou 325035, China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02854
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors gratefully acknowledge the National Natural
Science Foundation of China (21571144), the Zhejiang
Provincial Natural Science Foundation of China (LY18B020011
and LQ19B020004), and the Foundation of Zhejiang Educa-
tional Committee (Y201839490).
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