Lewis Acid Assisted Electrophilic Fluorine-Catalyzed Pinacol Rearrangement of Hydrobenzoin Substrates: One-Pot Synthesis of (±)-Latifine and (±)-Cherylline

Article abstract of DOI:10.1021/acs.joc.7b02587

A microwave-irradiated solvent-free pinacol rearrangement of hydrobenzoin substrates catalyzed by a combination of N-fluorobenzenesulfonimide and FeCl₃·6H₂O was developed. Its selectivity was first investigated by density functional theory (DFT) calculations. Then the functional group tolerance was examined by synthesizing a series of substrates designed based on the insight provided by the DFT calculations. The application of the methodology was demonstrated by the efficient one-pot synthesis of (±)-latifine and (±)-cherylline, both are 4-aryltetrahydroisoquinoline alkaloids isolated from Amaryllidacecae plants.

Full text of DOI:10.1021/acs.joc.7b02587

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Article
Lewis Acid-Assisted Electrophilic Fluorine-Catalyzed
Pinacol Rearrangement of Hydrobenzoin Substrates:
One-Pot Synthesis of (±)-Latifine and (±)-Cherylline
Hui Shi, Chuan Du, Xinhang Zhang, Fukai Xie, Xiaoyu Wang, Shanshan
Cui, Xiaoshi Peng, Maosheng Cheng, Bin Lin, and Yongxiang Liu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b02587 • Publication Date (Web): 10 Jan 2018
Downloaded from http://pubs.acs.org on January 10, 2018
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Lewis Acid-Assisted Electrophilic Fluorine-Catalyzed Pinacol
Rearrangement of Hydrobenzoin Substrates: One-Pot Synthesis of
(±)-Latifine and (±)-Cherylline
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Hui Shi,a,b Chuan Du,a,b Xinhang Zhang,a,b,c Fukai Xie,a,b Xiaoyu Wang,a,b Shanshan Cui,a,b
Xiaoshi Peng,a,b Maosheng Cheng,a,b Bin Lin,a,b∗ and Yongxiang Liua,b,c
∗
aKey Laboratory of StructureꢀBased Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry
of Education, Shenyang 110016, P. R. China.
bInstitute of Drug Research in Medicine Capital of China, Benxi 117000, P. R. China.
cWuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, P. R. China.
Abstract. A microwaveꢀirradiated solventꢀfree pinacol rearrangement of hydrobenzoin substrates
catalyzed by a combination of Nꢀfluorobenzenesulfonimide (NFSI) and FeCl3•6H2O was
developed. Its selectivity was first investigated by density functional theory (DFT) calculations.
Then the functional group tolerance was examined by synthesizing a series of substrates designed
based on the insight provided by the DFT calculations. The application of the methodology was
demonstrated by the efficient oneꢀpot synthesis of (±)ꢀlatifine and (±)ꢀcherylline, both are
4ꢀaryltetrahydroisoquinoline alkaloids isolated from Amaryllidacecae plants.
Introduction
The pinacol rearrangement is a classic transformation of vicinal diols leading to carbonyl
compounds. The uses of pinacol rearrangement and related transformations in the syntheses of
natural products and bioactive molecules were explored widely for their unique abilities in
constructing quaternary carbons and novel skeletons.1 Numerous efforts on developing mild and
environmentally friendly catalysts to replace hazardous stoichiometric reagents have been made
by utilizing solid acid catalysts and ionic liquids.2 However, circumvention of harsh conditions
and cumbersome procedures, predictable selectivity of the reaction, and utility of readily available
catalyst are still in urgent need for the further development of pinacol rearrangement under more
mild and robust conditions.
The precise control of selectivity of hydrobenzoin, a textbook substrate in various Brønsted
acidꢀ, Lewis acidꢀ and solid acidꢀcatalyzed pinacol rearrangements has remained a great challenge
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and has been influenced by many factors, such as catalysts, solvents, temperatures, etc.2f,3,4bꢀ4c The
resulting mixture of ketone and aldehyde, due to the similar migratory aptitude of phenyl group
and hydride is difficult to isolate, thus limiting the applications of this type of pinacol
rearrangement in organic synthesis. We intend to address this problem by tuning the electronic
nature of the phenyl groups in hydrobenzoin derivatives. Normally, the rearrangement can proceed
either via a concerted mechanism without a carbocation intermediate or via a stepwise mechanism
with a carbocation intermediate followed by a migration of the functional group in the presence of
strong Brønsted acids such as H2SO4, H3PO4 or Lewis acids like AlCl3.4 However, when the
migrating group is aryl, which facilitates the formation of carbocation, the stepwise mechanism is
predominantly favored.5 We therefore hypothesize that it is possible to orientate the formation of
carbocation by synthesizing the substrates, according to the mechanism of pinacol rearrangement,
with one electronꢀrich phenyl ring: the phenylꢀmigrated aldehyde product could be generated by
increasing the electron density of the other phenyl ring and the hydrideꢀmigrated ketone product
could be generated by decreasing electron density of the other phenyl ring.5 The hypothesis is
supported by DFT calculations performed by selecting two such types of substrates as examples
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Scheme 1. DFT Calculation on the Selectivity on the Pinacol Rearrangement of Hydrobenzoin
Substrates
prior to our pinacol rearrangement experiments.6 The computational results predicted that the
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formation of aldehyde product for the substrate was due to the migration of the phenyl ring and
the formation of ketone product for the substrate was due to the migration of the hydride based on
the calculated energy differences and the stability of the products (Scheme 1). The experiments
were designed with the substrates selected by following the computational predictions above. In
the end, the experimental results confirmed both our experimental design and computational
predictions.
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In recent studies, we have described a series of waterꢀtolerant Lewis acid catalysts,7 among
which NFSI was identified as a novel catalyst under the assistance of Lewis acids to catalyze
multiple kinds of transformations such as MeyerꢀSchuster rearrangement, BaeyerꢀVilliger
oxidation, Beckmann rearrangement, etc.7dꢀ7e The robust electrophilic fluorine catalysts, developed
by our group, were derived from the combination of NFSI and a variety of Lewis acids and could
shorten the reaction time, improve the yields and decrease the temperatures of a number of Lewis
acidꢀcatalyzed reactions markedly compared with those of reported with Lewis acids only.7e Our
precedent investigation, which revealed the Lewis acidity of the combination of NFSI and Lewis
acids and the action model between NFSI and Lewis acids, prompted us to examine the catalytic
ability of this novel catalyst in some reactions where harsh conditions are required such as pinacol
rearrangement described in this study. Based on the control of selectivity of hydrobenzoin
substrates suggested by DFT calculations, we aimed to develop
a practical and
selectivityꢀcontrollable NFSI/FeCl3•6H2Oꢀcatalyzed pinacol rearrangement of hydrobenzoin
substrates and to apply it to the efficient oneꢀpot synthesis of (±)ꢀlatifine and (±)ꢀcherylline, both
are 4ꢀaryltetrahydroisoquinoline alkaloids isolated from Amaryllidacecae plants. Compared with
the reported pinacol rearrangement of hydrobenzoin, this method provided a more mild and robust
condition for the controllable synthesis of both 2,2ꢀdiarylacetaldehydes and 2ꢀarylꢀ1ꢀarylethanones
only by changing the substitutents of the substrates.
Results and Discussion
At first, a model vicinal diol substrate 1a was synthesized to test the reaction potential of the
combination of 5 mol% NFSI and 1 mol% FeCl3•6H2O, the optimal conditions obtained in our
precedent study (Scheme 2). It was found that the combination of NFSI and FeCl3•6H2O catalyzed
the pinacol rearrangement of substrate 1a at 40 °C in 15 min under the irradiation of microwave in
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the absence of solvents with a yield of 80%. In contrast, as a control catalyst, 1 mol% FeCl3•6H2O
itself did not catalyze the reaction at the same temperature at all and showed no trace of reaction
even at 100 °C. When 5 mol% NFSI was used as the only catalyst in the rearrangement reaction,
lower yield (20%) was obtained under the same conditions.Those results were in agreement with
our previous observation in MeyerꢀSchuster rearrangement and Beckmann rearrangement.7e It is
worth mentioning that the NFSI/FeCl3•6H2O system is superior to the same quantity of Brønsted
acid such as H2SO4, which gives trace amount of product under the same condition.
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The DFT calculations were carried out after we developed the very first model reaction and
before we examined the full scope of the newly developed methodology. It was predicted that
without any substitutions on both phenyl groups on the substrate (case a), the reaction would need
to cross the barrier of 24.78 kcal/mol (relative to the starting material) if the hydride migrated and
the barrier of 15.61 kcal/mol if the phenyl group migrated. When both substitutions were
electronꢀdonating methoxy groups or electronꢀwithdrawing nitro groups on both phenyl groups
(case b and d), the barrier was predicted to be much lower when the aryl group migrated than
when the hydride migrated due to the reason that aryl groups had better migratory aptitude than
hydride, even with one electronꢀwithdrawing group on the phenyl group. Since the barrier was
much lower for aryl migration, that should be the path that the reaction would follow. Indeed that
was observed experimentally. When one substitution was electronꢀdonating methoxy group and
the other was electronꢀwithdrawing nitro group on the phenyl group (case c), hydride migration
was expected to happen because the ketone product was more thermodynamically stable than the
aldehyde product. Such prediction was also consistent with the experimental observation (Scheme
1).
Subsequently, the scope of the transformation under the NFSI/FeCl3•6H2O system was
examined by using a series of synthetic secondary vicinal diol substrates, including both
unsymmetrical and symmetrical ones, based on the predictions from the prior DFT calculations.
The unsymmetrical secondary vicinal diols 1a-1e were prepared using methods reported in the
literature8 and subjected to the standard conditions leading to, with yields of at least 80%,
corresponding 2,2ꢀdiarylacetaldehydes 2a-2e with the migration of electronꢀrich phenyl rings,
which can better stabilize the positivelyꢀcharged intermediates than electronꢀdeficient ones. The
symmetrical pinacol substrates 1f-1h with electronꢀrich substitutions on phenyl rings were then
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examined to afford the 2,2ꢀdiarylacetaldehydes 2f-2h with excellent yields as expected (Scheme
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2).
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Scheme 2. Substrate Scope of Pinacol Rearrangement Resulting in the Formation of
2,2ꢀDiarylacetaldehydes
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Next, we prepared some unsymmetrical secondary vicinal diols that bear both electronꢀrich
and electronꢀdeficient phenyl groups shown in Scheme 3 to examine the migratory rules further.
According to the general stepwise mechanism, the reaction will be initiated by the formation of
carbocation on the electronꢀrich benzyl position, and the migration of hydride or electronꢀdeficient
phenyl ring will result in aldehyde or ketone products. In the DFT calculations, the end product of
the hydride migration pathway was more stable than that of the electronꢀdeficient phenyl ring
migration pathway (Scheme 1). In agreement with the theoretical calculations, in all cases, the
exclusiveness of hydride migration yielding 2ꢀarylꢀ1ꢀarylethanone as the only products indicated
that the electronic nature of the aryl rings could control the migratory aptitude to afford different
products.
Scheme 3. Substrate Scopes of Pinacol Rearrangement to Yield 2ꢀArylꢀ1ꢀarylethanones
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Scheme 4. Substrate Scopes of Pinacol Rearrangement to Yield αꢀTrisubstituted Ketones
Lastly, the tertiary pinacol substrates were examined under this reaction conditions. The
unsymmetrical tertiary pinacol substrates 1q-1s were first prepared to test the scopes. It was found
that the benzyl carbocation was formed prior to the migration of proximal group to give
αꢀtrisubstituted ketones 2q-2s. The symmetrical tertiary pinacol substrates 1t-1w were then
designed to examine the scopes further and the results were similar to those of the substrates 1q-1s.
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The symmetrical tertiary substrates 1x-1z with four same aromatic substitutions also gave
αꢀtrisubstituted ketone products with excellent yields (Scheme 4).
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Scheme 5. Proposed Mechanism for the Formation of 2f and 2i
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Based on the current results and our previous study,7e a plausible mechanism for the diverted
pathway of unsymmetrical secondary vicinal diols was proposed in Scheme 5. Activation of
hydroxyl groups of the substrates 1f and 1i by electrophilic fluorine promoted the formation of
carbocation 1f-2 and 1i-2 on the electronꢀrich benzyl position in both substrates. The different
migratory aptitudes of substituted phenyl groups and hydride led to the formation of the phenyl
migration product 2f and the hydride migration product 2i respectively.
Inspired by the precise control of the products obtained in the NFSI/FeCl3•6H2Oꢀcatalyzed
pinacol rearrangement, we designed a practical synthetic route to the naturally occurring
isoqunoline alkaloids (±)ꢀlatifine and (±)ꢀcherylline.9 The pinacol substrates 3a and 3b were
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synthesized readily by a Wittig/epoxidation/ring opening oneꢀpot protocol utilizing substituted
benzaldehydes as starting materials. The syntheses of (±)ꢀlatifine (4a) and (±)ꢀcherylline (4b) were
achieved by the NFSI/FeCl3•6H2Oꢀcatalyzed pinacol rearrangement as the key step followed by
oneꢀpot reductive amination/PictetꢀSpengler and hydrogenation reactions with excellent yields, in
which four chemical bonds including two C−C and two C−N bonds were constructed and only one
isolation step was required (Scheme 6). The oneꢀpot synthetic method afforded a rapid access to
the isoqunoline natural products and analogues.
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Scheme 6. OneꢀPot Synthesis of (±)ꢀLatifine and (±)ꢀCherylline Using Pinacol Rearrangement as
the Key Step
Conclusions
A readily available and environmentally friendly NFSI/FeCl3•6H2O system in catalyzing pinacol
rearrangement under mild and neat conditions was developed. The functional group tolerance of
the methodology was examined by a series of designed substrates. The influence of electronic
effect on migration sequence was probed by both DFT calculations and experimental results. The
synthetic applications of the methodology were demonstrated by the oneꢀpot syntheses of two
alkaloid natural products (±)ꢀlatifine and (±)ꢀcherylline, affording a unique and efficient method in
the preparation of isoqunoline derivatives. The efforts on preparing bioactive small molecules by
the oneꢀpot method are currently underway in our laboratory.
Experimental Section
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General Experimental Methods. Reagents were obtained commercially and used without further
purification. Tetrahydrofuran was distilled from sodium under a nitrogen atmosphere. TLC
analysis of reaction mixtures was performed on silica gel Fꢀ254 TLC plates. Flash
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chromatography was performed using silica gel (200−300 mesh). H and 13C NMR spectra were
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recorded in CDCl3, DMSOꢀd6 or CD3OD on a 600 MHz instrument. HRꢀESIMS was carried out
with electrospray ionization (ESI) using a QꢀTOF mass spectrometer. IR spectra were recorded as
thin film on an FTꢀIR spectrometer. Melting points (mp) were tested on a capillary melting point
apparatus. Microwave reactions were performed using microwave oven CEM Discover in sealed
reaction vessels. The temperature was monitored using an internal vertically focused IR
temperature sensor.
General Procedures for the Synthesis of Propargylic Alcohols 1a-1e, 1i-1p.
Under argon atmosphere, the butyllithium (2.5 M in hexanes, 0.54 mL, 1.3 mmol) was added
to a solution of phosphonium bromide salts (1.3 mmol) in anhydrous THF at −20 °C and the
resulting red solution was stirred at this temperature for 1 h. A solution of the aldehydes (1.3 mmol)
in anhydrous THF was added dropwise and the resulting solution was allowed to warm to room
temperature for 2ꢀ6 h. The resulting suspension was poured into water and extracted with ethyl
acetate. The combined organic layers were washed with a saturated aqueous solution of NH4Cl
and brine, after drying over anhydrous Na2SO4, the solvent was removed in vacuo to give a crude
material, which was used without further purification in the next step.
The cis/transꢀstilbenes (2 mmol) obtained above were dissolved in dichloromethane (20 mL)
and the solution was cooled to 0 °C, then mꢀCPBA (863 mg, 5 mmol) was added. After stirring at
room temperature for 15 h, the mixture was extracted with dichloromethane. The combined
organic layers were washed with 5% NaHCO3 solution and brine. After drying over anhydrous
Na2SO4, the solvent was removed in vacuo to give a crude material.
The crude stilbene oxides were dissolved in THF (10 mL), then a solution of sodium
hydroxide (240 mg, 6 mmol) in water (5 mL) was added. After stirring at room temperature for 3 h,
the mixture was extracted with ethyl acetate. The combined organic layers were washed with a
saturated aqueous solution of NH4Cl and brine. After drying over anhydrous Na2SO4, the solvent
was removed in vacuo to give a crude material, which was purified by a flash column
chromatography on silica gel to afford the products 1a-1e, 1i-1p.
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1-(Benzo[d][1,3]dioxol-5-yl)-2-(4-methoxyphenyl)ethane-1,2-diol (1b). Purified by a flash
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column chromatography on silica gel with petroleum ether/ethyl acetate (3:1) as an eluent to give
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the product 1b (277 mg) as a white solid with a yield of 48%: mp 105.9–107.3 C; The ratio of
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major isomer and minor isomer is 5.6:1; 1H NMR (600 MHz, DMSOꢀd6) (major isomer) δ 7.01 (d,
J = 8.7 Hz, 2H), 6.74 (d, J = 8.7 Hz, 2H), 6.75–6.73 (m, 2H), 6.49 (dd, J = 8.0, 1.5 Hz, 1H), 5.92
(dd, J = 3.5, 0.8 Hz, 2H), 5.26 (d, J = 3.8 Hz, 1H), 5.21 (d, J = 3.7 Hz, 1H), 4.48–4.44 (m, 2H),
3.68 (s, 3H); (minor isomer) δ 7.14 (d, J = 8.7 Hz, 2H), 6.82–6.80 (m, 2H), 6.74 (d, J = 8.7 Hz,
2H), 6.64 (dd, J = 8.0, 1.5 Hz, 1H), 5.95 (s, 2H), 5.11 (d, J = 4.4 Hz, 1H), 5.06 (d, J = 4.4 Hz, 1H),
4.48–4.44 (m, 2H), 3.71 (s, 3H); 13C NMR (150 MHz, DMSOꢀd6) (major isomer) δ 158.0, 146.4,
145.8, 136.5, 134.3, 128.3, 120.5, 112.7, 107.6, 107.2, 100.5, 77.5, 77.2, 54.9; (minor isomer)
158.1, 146.5, 145.8, 137.4, 135.3, 128.4, 120.6, 112.7, 107.8, 107.1, 100.5, 76.8, 76.5, 55.0; IR
(thin film, cmꢀ1) 3394, 3071, 3009, 2900, 2837, 1612, 1516, 1488, 1442, 1250, 1178, 1037; HRMS
(ESI) m/z [M+Na]+ calcd. for C16H16NaO5 311.0895, found 311.0891.
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1-(4-(Benzyloxy)phenyl)-2-(3-bromo-4,5-dimethoxyphenyl)ethane-1,2-diol (1c). Purified by a
flash column chromatography on silica gel with petroleum ether/ethyl acetate (2:1) as an eluent to
give the product 1c (429 mg) as a yellow oil with a yield of 56%: 1H NMR (600 MHz, DMSOꢀd6)
δ 7.16 (d, J = 8.6 Hz, 2H), 7.08 (s, 1H), 6.95 (s, 1H), 6.79 (d, J = 8.6 Hz, 2H), 5.38 (d, J = 5.5 Hz,
1H), 5.17 (d, J = 5.4 Hz, 1H), 4.80 (t, J = 5.2 Hz, 1H), 4.61 (t, J = 5.1 Hz, 1H), 3.74 (s, 3H), 3.72
(s, 3H) , 3.70 (s, 3H); 13C NMR (150 MHz, DMSOꢀd6) δ 158.7, 148.7, 148.2, 135.2, 134.3, 128.2,
115.0, 113.2, 113.0, 112.3, 76.0, 75.8, 56.2, 55.9, 55.3; IR (thin film, cmꢀ1) 3424, 3000, 2923, 1607,
1508, 1251, 1157, 1030; HRMS (ESI) m/z [MꢀH]ꢀ calcd. for C17H18BrO5 381.0343, found
381.0335.
1-(Benzo[d][1,3]dioxol-5-yl)-2-(3,4,5-trimethoxyphenyl)ethane-1,2-diol (1d). Purified by a flash
column chromatography on silica gel with petroleum ether/ethyl acetate (2:1) as an eluent to give
o
the product 1d (306 mg) as a white solid with a yield of 44%: mp 102.7–122.5 C; The ratio of
major isomer and minor isomer is 7.7:1; 1H NMR (600 MHz, DMSOꢀd6) (major isomer) δ 6.85 (d,
J = 1.4 Hz, 1H), 6.78 (d, J = 7.9 Hz, 1H), 6.69 (dd, J = 8.0, 1.5 Hz, 1H), 6.53 (s, 2H), 5.96 (dd, J =
4.3, 0.9 Hz, 2H), 5.20–5.08 (m, 2H), 4.50–4.42 (m, 2H), 3.70 (s, 6H), 3.63 (s, 3H); (minor isomer)
δ 6.75 – 6.72 (m, 2H), 6.59 (dd, J = 8.0, 1.4 Hz, 1H), 6.41 (s, 2H), 5.93 (dd, J = 5.5, 0.8 Hz, 2H),
5.30 (d, J = 4.0 Hz, 1H), 5.25 (d, J = 4.0 Hz, 1H), 4.49–4.44 (m, 2H), 3.65 (s, 6H), 3.60 (s, 3H);
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13C NMR (150 MHz, DMSOꢀd6) (major isomer) δ 152.1, 146.5, 145.9, 139.1, 137.4, 136.2, 120.7,
107.9, 107.1, 104.6, 100.5, 77.1, 76.8, 60.0, 55.7; (minor isomer) 152.0, 146.5, 145.8, 138.2,
136.8, 136.1, 120.4, 107.6, 107.2, 104.4, 100.5, 77.7, 77.4, 59.8, 55.0; IR (thin film, cmꢀ1) 3501,
3413, 2933, 2878, 1632, 1597, 1501, 1483, 1462, 1420, 1238, 1126, 1037; HRMS (ESI) m/z
[M+Na]+ calcd. for C18H20NaO7 371.1107, found 371.1097.
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1-(4-Methoxyphenyl)-2-(4-nitrophenyl)ethane-1,2-diol (1i). Purified by
a flash column
chromatography on silica gel with petroleum ether/ethyl acetate (3:1) as an eluent to give the
product 1i (260 mg) as a yellow oil with a yield of 45%: The ratio of major isomer and minor
isomer is 1.3:1; 1H NMR (600 MHz, DMSOꢀd6) (major isomer) δ 8.05 (d, J = 8.7 Hz, 2H), 7.36 (d,
J = 8.7 Hz, 2H), 7.01 (d, J = 8.6 Hz, 2H), 6.74 (d, J = 8.6 Hz, 2H), 5.65 (d, J = 4.4 Hz, 1H), 5.43
(d, J = 4.4 Hz, 1H), 4.76 (t, J = 5.0 Hz, 1H), 4.62 (t, J = 5.0 Hz, 1H), 3.68 (s, 3H); (minor isomer)
8.12 (d, J = 8.7 Hz, 2H), 7.48 (d, J = 8.7 Hz, 2H), 7.15 (d, J = 8.6 Hz, 2H), 6.82 (d, J = 8.6 Hz,
2H), 5.54 (d, J = 4.8 Hz, 1H), 5.30 (d, J = 4.8 Hz, 1H), 4.68 (t, J = 5.0 Hz, 1H), 4.55 (t, J = 5.0 Hz,
1H), 3.71 (s, 3H); 13C NMR (150 MHz, DMSOꢀd6) (major isomer) δ 158.6, 151.1, 146.7, 134.0,
128.7, 122.7, 113.1, 76.9, 76.9, 55.3; (minor isomer) 158.6, 151.8, 146.7, 135.1, 128.9, 128.6,
122.8, 113.2, 76.8, 76.6, 55.3; IR (thin film, cmꢀ1) 3460, 2918, 2846, 1604, 1512, 1345, 1244,
1075, 1023; HRMS (ESI) m/z [M+Na]+ calcd. for C15H15NNaO5 312.0842, found 312.0845.
1-(4-Methoxyphenyl)-2-(2-nitrophenyl)ethane-1,2-diol (1j). Purified by
a flash column
chromatography on silica gel with petroleum ether/ethyl acetate (3:1) as an eluent to give the
o
1
product 1j (243 mg) as a yellow solid with a yield of 42%: mp 96–98 C; H NMR (600 MHz,
DMSOꢀd6) δ 7.75 (dd, J = 8.1, 0.8 Hz, 1H), 7.59 – 7.52 (m, 2H), 7.44 – 7.39 (m, 1H), 7.00 (d, J =
8.6 Hz, 2H), 6.75 (d, J = 8.7 Hz, 2H), 5.66 (d, J = 5.2 Hz, 1H), 5.36 (d, J = 5.3 Hz, 1H), 5.25 (t, J
= 5.0 Hz, 1H), 4.64 (t, J = 5.0 Hz, 1H), 3.69 (s, 3H); 13C NMR (150 MHz, DMSOꢀd6) δ 158.6,
148.8, 137.3, 134.4, 132.4, 130.3, 128.2, 128.1, 123.7, 113.2, 75.9, 72.0, 55.3; IR (thin film, cmꢀ1)
3418, 2920, 2360, 1609, 1516, 1345, 1249, 1030; HRMS (ESI) m/z [M+Na]+ calcd. for
C15H15NNaO5 312.0842, found 312.0845.
1-(4-Methoxyphenyl)-2-(3-nitrophenyl)ethane-1,2-diol (1k). Purified by
a flash column
chromatography on silica gel with petroleum ether/ethyl acetate (2:1) as an eluent to give the
o
product 1k (225 mg) as a yellow solid with a yield of 39%: mp 69–71 C; The ratio of major
isomer and minor isomer is 3:1; 1H NMR (600 MHz, DMSOꢀd6) (major isomer) δ 8.03–8.01 (m,
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1H), 7.95–7.94 (m, 1H), 7.52–7.45 (m, 2H), 7.02 (d, J = 8.6 Hz, 2H), 6.74 (d, J = 8.6 Hz, 2H),
5.66 (d, J = 4.6 Hz, 1H), 5.42 (d, J = 4.6 Hz, 1H), 4.79 (t, J = 4.9 Hz, 1H), 4.63 (t, J = 4.9 Hz, 1H),
3.68 (s, 3H); (minor isomer) 8.10–8.06 (m, 2H), 7.62–7.52 (m, 2H), 7.16 (d, J = 8.6 Hz, 2H), 6.82
(d, J = 8.6 Hz, 2H), 5.56 (d, J = 4.6 Hz, 1H), 5.30 (d, J = 4.6 Hz, 1H), 4.68 (t, J = 5.6 Hz, 1H),
4.55 (t, J = 5.6 Hz, 1H), 3.72 (s, 3H); 13C NMR (150 MHz, DMSOꢀd6) (major isomer) δ 158.2,
147.1, 145.0, 133.9, 133.7, 128.6, 128.2, 121.7, 121.6, 112.7, 76.4, 76.2, 55.0; (minor isomer)
158.3, 147.2, 145.7, 134.8, 134.3, 128.7, 128.3, 122.0, 121.6, 112.9, 76.4, 76.2, 55.0; IR (thin film,
cmꢀ1) 3414, 3089, 3004, 2916, 2838, 1612, 1528, 1351, 1249, 1176; HRMS (ESI) m/z [M+Na]+
calcd. for C15H15NNaO5 312.0842, found 312.0845.
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4-(1,2-Dihydroxy-2-(4-methoxyphenyl)ethyl)benzonitrile (1l). Purified by a flash column
chromatography on silica gel with petroleum ether/ethyl acetate (2:1) as an eluent to give the
product 1l (231 mg) as a white solid with a yield of 43%: mp 63–65 oC; The ratio of major isomer
and minor isomer is 1.6:1;1H NMR (600 MHz, DMSOꢀd6) (major isomer) δ 7.66–7.61 (m, 2H),
7.27 (d, J = 8.2 Hz, 2H), 6.99 (d, J = 8.6 Hz, 2H), 6.76–6.72 (m, 2H), 5.58 (d, J = 4.5 Hz, 1H),
5.39 (d, J = 4.3 Hz, 1H), 4.70–4.67 (m, 1H), 4.60–4.56 (m, 1H), 3.68 (s, 3H); (minor isomer)
7.71–7.67 (m, 2H), 7.39 (d, J = 8.2 Hz, 2H), 7.12 (d, J = 8.6 Hz, 2H), 6.85–6.78 (m, 2H), 5.46 (d,
J = 4.8 Hz, 1H), 5.26 (d, J = 4.6 Hz, 1H), 4.64–4.60 (m, 1H), 4.55–4.49 (m, 1H), 3.71 (s, 3H); 13
C
NMR (150 MHz, DMSOꢀd6) (major isomer) δ 158.2, 148.4, 133.7, 131.2, 128.2, 128.1, 119.1,
112.7, 109.3, 76.8, 76.5, 54.9; (minor isomer) 158.2, 149.2, 134.7, 131.2, 128.4, 128.3, 119.1,
112.8, 109.3, 76.6, 76.2, 55.0; IR (thin film, cmꢀ1) 3362, 3002, 2918, 2842, 2227, 1610, 1512,
1247, 1027; HRMS (ESI) m/z [MꢀH]ꢀ calcd. for C16H14NO3 268.0979, found 268.0978.
1-(2,3-Dichlorophenyl)-2-(4-methoxyphenyl)ethane-1,2-diol (1m). Purified by a flash column
chromatography on silica gel with petroleum ether/ethyl acetate (3:1) as an eluent to give the
product 1m (318 mg) as a colorless oil with a yield of 51%: The ratio of major isomer and minor
isomer is 6.3:1;1H NMR (600 MHz, DMSOꢀd6) (major isomer) δ 7.48 (d, J = 7.8 Hz, 1H), 7.30 (d,
J = 7.8 Hz, 1H), 7.25 (t, J = 7.8 Hz, 1H), 7.11 (d, J = 8.5 Hz, 2H), 6.80 (d, J = 8.5 Hz, 2H), 5.53 (d,
J = 4.4 Hz, 1H), 5.31 (d, J = 4.4 Hz, 1H), 5.11 (t, J = 5.2 Hz, 1H), 4.62 (t, J = 5.2 Hz, 1H), 3.71 (s,
3H); (minor isomer) δ 7.58 (d, J = 7.8 Hz, 1H), 7.50 (d, J = 7.8 Hz, 1H), 7.35 (t, J = 7.8 Hz, 1H),
7.19 (d, J = 8.5 Hz, 2H), 6.82 (d, J = 8.5 Hz, 2H), 5.58 (d, J = 5.6 Hz, 1H), 5.30 (d, J = 5.6 Hz,
1H), 5.01 (t, J = 5.0 Hz, 1H), 4.65 (t, J = 5.0 Hz, 1H), 3.71 (s, 3H); 13C NMR (150 MHz,
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DMSOꢀd6) (major isomer) δ 158.2, 143.4, 134.6, 130.9, 129.3, 128.8, 128.3, 127.8, 127.5, 112.9,
74.9, 74.1, 56.0; (minor isomer) 158.3, 143.6, 134.3, 130.8, 130.1, 128.7, 128.6, 127.3, 127.4,
112.7, 75.4, 73.6, 56.0; IR (thin film, cmꢀ1) 3411, 3000, 2955, 2933, 1612, 1513, 1250, 1177, 1035;
HRMS (ESI) m/z [M+Na]+ calcd. for C15H14Cl2NaO3 335.0212, found 335.0214.
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1-(2-Bromo-5-fluorophenyl)-2-(4-methoxyphenyl)ethane-1,2-diol (1o). Purified by a flash
column chromatography on silica gel with petroleum ether/ethyl acetate (3:1) as an eluent to give
the product 1o (292 mg) as a yellow solid with a yield of 43%: mp 56–58 oC; 1H NMR (600 MHz,
DMSOꢀd6) δ 7.53 (dt, J = 10.0, 5.0 Hz, 1H), 7.06–6.97 (m, 4H), 6.80–6.76 (m, 2H), 5.57 (d, J =
4.8 Hz, 1H), 5.34 (d, J = 4.4 Hz, 1H), 4.97 (t, J = 4.5 Hz, 1H), 4.63 (t, J = 4.7 Hz, 1H), 3.70 (s,
3H); 13C NMR (150 MHz, DMSOꢀd6) δ 161.2 (d, 1JCF = 243.3 Hz), 158.3, 144.8 (d, 3JCF = 7.1 Hz),
133.9, 133.2 (d, 3JCF = 7.9 Hz), 128.6, 117.1 (d, 4JCF = 2.7 Hz), 116.2 (d, 2JCF = 23.5 Hz), 115.8 (d,
2JCF = 22.7 Hz), 112.7, 75.2, 75.1, 55.0; IR (thin film, cmꢀ1) 3415, 3073, 2934, 2837, 1612, 1580,
1250, 1176, 1027; HRMS (ESI) m/z [M+Na]+ calcd. for C15H14BrFNaO3 363.0003, found
363.0011.
1-(2-Bromo-5-chlorophenyl)-2-(4-methoxyphenyl)ethane-1,2-diol (1p). Purified by a flash
column chromatography on silica gel with petroleum ether/ethyl acetate (3:1) as an eluent to give
1
the product 1p (313 mg) as a yellow oil with a yield of 44%: H NMR (600 MHz, DMSOꢀd6) δ
7.52 (d, J = 8.5 Hz, 1H), 7.25 (d, J = 2.6 Hz, 1H), 7.21 (dd, J = 8.5, 2.7 Hz, 1H), 7.06 (d, J = 8.6
Hz, 2H), 6.79 (d, J = 8.6 Hz, 2H), 5.57 (d, J = 4.8 Hz, 1H), 5.34 (d, J = 4.2 Hz, 1H), 4.96 (t, J =
5.0 Hz, 1H), 4.62 (d, J = 4.2 Hz, 1H), 3.71 (s, 3H); 13C NMR (150 MHz, DMSOꢀd6) δ 158.7,
144.7, 134.4, 133.6, 132.3, 129.7, 128.9, 128.8, 121.5, 113.1, 75.7, 75.5, 55.4; IR (thin film, cmꢀ1)
3369, 3003, 2918, 2842, 1644, 1512, 1459, 1247, 1026; HRMS (ESI) m/z [MꢀH]ꢀ calcd. for
C15H13BrClO3 354.9742, found 354.9738.
General Procedures for the Synthesis of Propargylic Alcohols 1f-1g.
A suspension of benzaldehydes (1.89 mmol) and magnesium turnings (1.0 g, 42 mmol) in
ammonium chloride aqueous solution (0.1 M, 10 mL) was stirred overnight under an atmosphere
of air at room temperature. The reaction was quenched with dilute HCl solution and extracted with
ethyl acetate three times. The combined organic layers were washed with a saturated aqueous
solution of NaHCO3 and brine. After drying over anhydrous Na2SO4, the solvent was removed in
vacuo, and the residue was purified by a flash column chromatography on silica gel to afford the
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General Procedures for the Synthesis of Propargylic Alcohol 1h.
The solution of piperonyl aldehyde (1.5 g, 10 mmol) and magnesium turnings (1.2 g, 50
mmol) in methanol was added in a flask, which was fitted with a reflux condenser. One seed
iodine was added while stirring the solution vigorously at room temperature. A vigorous reaction
occurred after a short while. After the reaction was complete (monitored by TLC), the mixture was
quenched with 2 M acetic acid and extracted with ethyl acetate three times. The combined organic
layers were washed with a saturated aqueous solution of NaHCO3 and brine. After drying over
anhydrous Na2SO4, the solvent was removed in vacuo, and the residue was purified by a flash
column chromatography on silica gel to afford the product 1h.
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General Procedures for the Synthesis of Propargylic Alcohols 1t-1w.
The solution of aryl ketones (10 mmol), aluminium powder (0.81 g, 30 mmol) and KOH (5.0
g, 90 mmol) in methanol (10 mL) was added in a flask, which was fitted with a reflux condenser.
The mixture was stirred at room temperature for 3 h. After the reaction was complete (monitored
by TLC), the reaction mixture was filtered to remove unreacted aluminium powder and water was
added to the filtrate. The filtrate was extracted with dichloromethane three times and the combined
organic layers were washed with brine. After drying over anhydrous Na2SO4, the solvent was
removed in vacuo, and the residue was purified by a flash column chromatography on silica gel to
afford the products 1t-1w.
General Procedures for the Synthesis of Propargylic Alcohols 1x-1z.
A mixture of diaryl ketones (10 mmol), Zn powder (5.2 g, 80 mmol), ZnCl2 (1.1 g, 8 mmol)
and 50% aqueous solution of THF (10 mL) was added in a flask and stirred at room temperature
for 3 h. After the reaction was complete (monitored by TLC), the reaction mixture was combined
with 3 N HCl (5 mL) and filtered to remove the Zn powder. The filtrate was extracted with ethyl
acetate three times and the combined organic layers were washed with brine. After drying over
anhydrous Na2SO4, the solvent was removed in vacuo to give a crude material, which was purified
by a flash column chromatography on silica gel to afford the products 1xꢀ1z.
General Procedures for the Synthesis of Propargylic Alcohols 1q-1s.
To a 100 mL roundꢀbottomed flask equipped with a dropping funnel was added magnesium
turnings (0.6 g, 25 mmol) in dry DMF (25 mL). After cooling the flask in an ice–salt bath, a
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mixture of aromatic ketone (5 mmol), acetone (2.9 g, 50 mmol) and trimethylchlorosilane (2.7 g,
25 mmol) in DMF (20 mL) was added under magnetic stirring over 30 min. The reaction mixture
was allowed to stir at room temperature overnight and was extracted with ethyl acetate. After
evaporation of the solvent under reduced pressure, the crude material was dissolved into methanol
with stirring. A 5% aqueous solution of sulfuric acid was carefully added into the methanol
solution and the reaction mixture was stirred for 6 h at room temperature. After neutralization, the
reaction mixture was extracted with ethyl acetate. The combined organic layers were washed with
a saturated aqueous solution of NaHCO3 and brine. The combined extracts were dried over
anhydrous Na2SO4, the solvent was removed in vacuo, and the residue was purified by a flash
column chromatography on silica gel to afford the products 1q-1s.
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General Procedures for the Synthesis of Aldehydes and Ketones 2a-2z.
A mixture of FeCl3•6H2O (0.3 mg, 1 umol), NFSI (1.6 mg, 5 umol) and diols 1a-1z (0.1
mmol) was stirred for 5 min. Then the mixture was irradiated under microwaves for 15 min until
the starting material disappeared (monitored by TLC). The crude mixture was purified by a flash
column chromatography on silica gel to afford the products 2a-2z.
2-(Benzo[d][1,3]dioxol-5-yl)-2-(4-methoxyphenyl)acetaldehyde (2b). Purified by a flash column
chromatography on silica gel with petroleum ether/ethyl acetate (20:1) as an eluent to give the
product 2b (24 mg) as a colorless oil with a yield of 88%: 1H NMR (600 MHz, CDCl3) δ 9.87 (d, J
= 2.4 Hz, 1H), 7.15–7.10 (m, 2H), 6.94–6.89 (m, 2H), 6.80 (d, J = 7.9 Hz, 1H), 6.69–6.64 (m, 2H),
5.95 (s, 2H), 4.75 (d, J = 2.4 Hz, 1H), 3.81 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 198.7, 159.3,
148.4, 147.3, 130.5, 130.4, 128.4, 122.5, 114.7, 109.6, 108.8, 101.4, 63.0, 55.5; IR (thin film, cmꢀ1)
3423, 2927, 2837, 2721, 1723, 1649, 1632, 1609, 1511, 1487, 1440, 1253; HRMS (ESI) m/z
[M+Na]+ calcd. for C16H14NaO4 293.0790, found 293.0787.
2-(3-Bromo-4,5-dimethoxyphenyl)-2-(4-methoxyphenyl) acetaldehyde (2c). Purified by a flash
column chromatography on silica gel with petroleum ether/ethyl acetate (30:1) as an eluent to give
the product 2c (34 mg) as a colorless oil with a yield of 94%: 1H NMR (600 MHz, CDCl3) δ 9.94
(s, 1H), 7.27 (s, 1H), 7.15 (d, J = 8.7 Hz, 2H), 7.10 (s, 1H), 6.93 (d, J = 8.7 Hz, 2H), 6.61 (s, 1H),
5.34 (s, 1H); 13C NMR (150 MHz, CDCl3) δ 198.2, 159.1, 148.9, 148.5, 130.4, 128.3, 127.1, 115.8,
115.4, 114.4, 113.1, 62.1, 56.1, 56.0, 55.2; IR (thin film, cmꢀ1) 3447, 2921, 2850, 1646, 1507,
1458, 1383, 1260; HRMS (ESI) m/z [M+Na]+ calcd. for C17H17BrNaO4 387.0202, found
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2-(Benzo[d][1,3]dioxol-5-yl)-2-(3,4,5-trimethoxyphenyl)acetaldehyde (2d). Purified by a flash
column chromatography on silica gel with petroleum ether/ethyl acetate (15:1) as an eluent to give
the product 2d (29 mg) as a colorless oil with a yield of 81%: 1H NMR (600 MHz, CDCl3) δ 9.87
(d, J = 2.5 Hz, 1H), 6.82 (d, J = 7.9 Hz, 1H), 6.71–6.66 (m, 2H), 6.40 (s, 2H), 5.97 (s, 2H), 4.73 (d,
J = 2.5 Hz, 1H), 3.84 (s, 3H), 3.82 (s, 6H); 13C NMR (150 MHz, CDCl3) δ 198.3, 153.9, 148.4,
147.4, 137.7, 131.9, 129.9, 122.6, 109.6, 108.9, 106.4, 101.5, 63.8, 61.1, 56.4; IR (thin film, cmꢀ1)
3432, 2937, 2838, 2724, 1723, 1651, 1632, 1609, 1589, 1488, 1419, 1245; HRMS (ESI) m/z
[M+Na]+ calcd. for C18H18NaO6 353.1001, found 353.0997.
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2-(4-Methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)acetaldehyde (2e). Purified by a flash column
chromatography on silica gel with petroleum ether/ethyl acetate (10:1) as an eluent to give the
product 2e (30 mg) as a colorless oil with a yield of 96%: 1H NMR (600 MHz, DMSOꢀd6) δ 9.90
(d, J = 2.0 Hz, 1H), 7.24–7.19 (m, 1H), 6.96–6.90 (m, 1H), 6.59 (d, J = 11.1 Hz, 1H), 4.94 (d, J =
1.8 Hz, 1H), 3.73 (s, 6H), 3.73 (s, 3H), 3.63 (s, 3H); 13C NMR (150 MHz, DMSOꢀd6) δ 200.3,
158.8, 153.5, 137.0, 133.5, 130.5, 129.5, 114.5, 106.8, 62.6, 60.4, 56.3, 55.4; IR (thin film, cmꢀ1)
3448, 2935, 2839, 1725, 1648, 1586, 1508, 1460, 1414, 1254; HRMS (ESI) m/z [MꢀH]ꢀ calcd. for
C18H19O5 315.1238, found 315.1241.
2,2-Bis(3,4,5-trimethoxyphenyl)acetaldehyde (2g). Purified by a flash column chromatography on
silica gel with petroleum ether/ethyl acetate (20:1) as an eluent to give the product 2g (36 mg) as a
colorless oil with a yield of 95%: 1H NMR (600 MHz, DMSOꢀd6) δ 9.93 (d, J = 2.1 Hz, 1H), 6.65
(s, 4H), 4.89 (d, J = 2.0 Hz, 1H), 3.75 (s, 12H), 3.63 (s, 6H); 13C NMR (150 MHz, DMSOꢀd6) δ
200.3, 153.4, 137.1, 133.3, 106.8, 63.5, 60.4, 56.4; IR (thin film, cmꢀ1) 3425, 2920, 2850, 1723,
1590, 1506, 1461, 1417; HRMS (ESI) m/z [MꢀH]ꢀ calcd. for C20H23O7 375.1449, found 375.1447.
1-(2-Bromo-5-chlorophenyl)-2-(4-methoxyphenyl)ethanone (2p). Purified by a flash column
chromatography on silica gel with petroleum ether/ethyl acetate (20:1) as an eluent to give the
product 2p (21 mg) as a colorless oil with a yield of 63%: 1H NMR (600 MHz, CDCl3) δ 7.54–
7.51 (m, 1H), 7.28–7.23 (m, 2H), 7.17–7.13 (m, 2H), 6.89–6.85 (m, 2H), 4.16 (s, 2H), 3.80 (s, 3H);
13C NMR (150 MHz, CDCl3) δ 200.6, 158.8, 142.7, 134.6, 133.6, 130.7, 128.4, 124.8, 116.4,
114.1, 55.2, 48.4; IR (thin film, cmꢀ1) 3447, 3066, 3002, 2957, 2930, 2837, 1701, 1663, 1607,
1512, 1458, 1250, 1175; HRMS (ESI): m/z [MꢀH]ꢀ calcd. for C15H11BrClO2 336.9636, found
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Procedures for the One-Pot Synthesis of (±)ꢀLatifine and (±)ꢀCherylline.
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The aldehydes 3a-1 and 3b-1 were prepared according to the general procedures for the
synthesis of aldehydes and ketones 2aꢀ2z.
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To a solution of the acetaldehyde 3a-1 or 3b-1 (1.5 mmol) in a mixture of anhydrous DCM
and MeOH (20 mL, 1:1, v/v) was added a solution of methylamine in THF (2 M, 3.8 mL, 7.5
mmol) at 0 °C and the resulting transparent solution was stirred under a nitrogen atmosphere for 2
h at room temperature. Then NaBH4 (113 mg, 3 mmol) was added and the mixture was stirred at
room temperature for 2 h. After the reaction was complete (monitored by TLC), the mixture was
diluted with DCM. The combined organic layers were washed with saturated aqueous NH4Cl
solution and brine. After drying over anhydrous Na2SO4, the solvent was removed in vacuo to give
the crude product 3a-3 or 3b-3 to be used in the next step without further purification.
A mixture of the amine 3a-3 or 3b-3 (1.5 mmol), formaldehyde (69 mg, 2.3 mmol) and acetic
acid (8 mL) was stirred at 90 °C under a nitrogen atmosphere for 4 h. After completion of the
reaction (monitored by TLC), it was cooled to room temperature. The reaction mixture was
basified with a saturated aqueous solution of NaHCO3. This basified solution was extracted by
ethyl acetate. The combined organic layers were washed with a saturated aqueous solution of
NH4Cl and brine. After drying over anhydrous Na2SO4, the solvent was removed in vacuo to give
a crude product 3a-4 or 3b-4 to be used in the next step without further purification.
To a solution of the crude product 3a-4 or 3b-4 (1.5 mmol) obtained above in EtOH (5 mL)
was added 10% Pd/C (14.5 mg) at room temperature and the mixture was stirred under a hydrogen
atmosphere at the same temperature for 6 h. After the reaction completed, the insoluble material
was removed by filtration. The filtrate was concentrated and purified by a flash column
chromatography on silica gel with CHCl3/MeOH (10:1, v/v) as eluent to give the product 4a or 4b.
The spectroscopic data are identical with those reported.9aꢀ9b
4-(4-Hydroxyphenyl)-6-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinolin-5-ol, acetate salt (4a).
Purified by a flash column chromatography on silica gel with dichloromethane/methyl alcohol
(10:1) as an eluent to give the product 4a (256 mg) as a colorless oil with a yield of 60%: 1H NMR
(600 MHz, CD3OD) δ 6.90 (t, J = 8.1 Hz, 3H), 6.68 (dd, J = 11.8, 8.5 Hz, 3H), 4.43 (t, J = 6.2 Hz,
1H), 4.07 (d, J = 14.5 Hz, 1H), 3.90 (d, J = 14.6 Hz, 1H), 3.82 (s, 3H), 3.36 (dd, J = 12.1, 6.2 Hz,
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1H), 3.08 (dd, J = 12.1, 6.3 Hz, 1H), 2.65 (s, 3H), 1.92 (s, 3H); 13C NMR (150 MHz, CD3OD) δ
177.4, 157.0, 148.3, 145.7, 135.1, 129.9, 125.3, 122.7, 117.9, 116.1, 111.6, 61.6, 57.5, 56.5, 44.7,
39.8, 22.2.
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4-(4-Hydroxyphenyl)-6-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ol, acetate salt (4b).
Purified by a flash column chromatography on silica gel with dichloromethane/methyl alcohol
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(10:1) as an eluent to give the product 4b (258 mg) as a colorless oil with a yield of 61%: H
NMR (600 MHz, CD3OD) δ 7.02 (d, J = 8.3 Hz, 2H), 6.76 (d, J = 8.3 Hz, 2H), 6.59 (s, 1H), 6.35
(s, 1H), 4.27 (dd, J = 10.5, 6.0 Hz, 1H), 4.00 (d, J = 14.6 Hz, 1H), 3.87 (d, J = 14.6 Hz, 1H), 3.60
(s, 3H), 3.34 (d, J = 6.0 Hz, 1H), 2.83 (t, J = 11.4 Hz, 1H), 2.67 (s, 3H), 1.92 (s, 2H); 13C NMR
(150 MHz, CD3OD) δ 178.5, 157.7, 148.6, 146.7, 134.5, 131.1, 128.5, 125.3, 116.5, 113.5, 112.8,
61.5, 57.5, 56.2, 44.6, 44.4, 22.8.
Computational Methods.
All of the DFT calculations conducted in this study were carried out using the GAUSSIAN 09
series of programs. DFT method B3LYP with a standard 6ꢀ31G (d) basis set was used for the
geometry optimizations. The local minima and transition state were confirmed by frequency
analysis with zero negative frequency and one negative frequency respectively.
ASSOCIATED CONTENT
1
The Supporting Information is available free of charge on the ACS Publications website. H and
13C NMR spectra for all compounds (PDF), the computational details.
AUTHOR INFORMATION
Corresponding Author
Email: randybinlin@gmail.com; yongxiang.liu@syphu.edu.cn.
ORCID
Yongxiang Liu: 0000ꢀ0003ꢀ0364ꢀ0137
Notes
The authors declare no competing financial interest.
Acknowledgements
We are grateful to the Natural Science Foundation of Liaoning Province of China (NO.
20170540855) and the foundation of Liaoning Province Education Administration of China (NO.
2017LQN08) for financial support. We acknowledge the program for innovative research team of
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the Ministry of Education and the program for Liaoning innovative research team in university.
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