Electrochemical Trifluoromethylation of Glycals

Article abstract of DOI:10.1021/acs.joc.1c01318

Carbohydrates play essential roles in various physiological and pathological processes. Trifluoromethylated compounds have wide applications in the field of medicinal chemistry. Herein, we report a practical and efficient trifluoromethylation of glycals b

Full text of DOI:10.1021/acs.joc.1c01318

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Electrochemical Trifluoromethylation of Glycals
Miao Liu, Zhao-Xiang Luo, Tian Li, De-Cai Xiong,* and Xin-Shan Ye*
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ABSTRACT: Carbohydrates play essential roles in various physiological and
pathological processes. Trifluoromethylated compounds have wide applications
in the field of medicinal chemistry. Herein, we report a practical and efficient
trifluoromethylation of glycals by an electrochemical approach using
CF3SO2Na as the trifluoromethyl source and MnBr2 as the redox mediator.
A variety of trifluoromethylated glycals bearing different protective groups are
obtained in 60−90% yields with high regioselectivity. The successful capture of
a CF3 radical indicates that a radical mechanism is involved in this reaction.
Scheme 1. Electrochemical Trifluoromethylation
arbohydrates mainly exist in the form of glycoconjugates
and polysaccharides. They participate in many critical
C
biological processes such as immune response, inflammation,
virus infection, and sperm−egg recognition.1 Thus, carbohy-
drate-based drug discovery is becoming one of the frontiers in
medicinal chemistry. However, the druggability of most natural
carbohydrates is not good due to their structural complexity,
weak metabolic stability, and low biological activity.2 Therefore,
the structural modification of carbohydrates is crucial for the
identification of new carbohydrate-related drugs.3
Trifluoromethylation of bioactive natural compounds has
emerged as one of the promising modification strategies for drug
discovery.4 The introduction of the trifluoromethyl (CF3) group
could usually improve the lipophilicity, metabolic stability, and
bioavailability of compounds.5 As a result, the development of
efficient methods for the preparation of CF3-containing
compounds is in great demand. In the past few years, organic
electrochemistry has represented an environmentally friendly
and powerful alternative to traditional redox methods, wherein
the use of extra oxidants or reductants could be reduced or even
avoided.6 In this context, electro-trifluoromethylation via a free
radical mechanism has been widely studied and turned out to be
highly practical. Various trifluoromethylating reagents such as
CF3SO2Cl,7 CF3COOH,8 CF3SO2Na (Langlois’ reagent),9 and
Zn(CF3SO2)2 (Baran’s reagent)10 could be easily electrolyzed to
generate a reactive trifluoromethyl radical involving a diversity of
trifluoromethylations of alkenes,11 (hetero)arenes,12 vinyl
carboxylic acids,13 and thiophenols14 (Scheme 1a,b). Although
the trifluoromethylated endo- and exoglycals via copper and
photoredox catalysis have been successfully synthesized through
a radical mechanism,15 the electrochemical trifluoromethylation
of carbohydrates has not been reported so far.
an electrochemical trifluoromethylation of glycals using the
readily available CF3SO2Na as the trifluoromethyl source and
MnBr2 as the redox mediator (Scheme 1c).
Initially, benzylated glucal 1a was chosen as the model
substrate to evaluate the feasibility of the electrochemical
trifluoromethylation process using CF3SO2Na (2a) as the
trifluoromethyl (CF3) source, Pt as the anode and cathode, and
dry CH3CN as the solvent under a constant electric current of 2
mA at room temperature in an undivided cell (Table 1 and Table
Special Issue: Electrochemistry in Synthetic Organic
Chemistry
CF3SO2Na, as an inexpensive, readily available, and bench-
stable trifluoromethyl source, has attracted great attention and
has been widely used to prepare diverse trifluormethylated
compounds in the electrochemical trifluoromethylation.16 In
continuation of our research interests17 in the synthesis of
carbohydrates and carbohydrate-related drugs, we herein report
Received: June 5, 2021
https://doi.org/10.1021/acs.joc.1c01318
© XXXX American Chemical Society
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A

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Note
a
12−14). Meanwhile, when water was used as the cosolvent, the
corresponding lactols were also detected in the reaction
mixtures. Bu4NOTf, Bu4NPF6, or Me4NClO4 instead of
Bu4NClO4 as the supporting electrolyte also showed a decreased
conversion (Table 1, entries 15−17). Only 14% yield of the
desired product was detected in the absence of MnBr2 (Table 1,
entry 18). The yield of the electrochemical reaction declined
sharply in an atmosphere of air, indicating an inert atmosphere
was essential (Table 1, entry 19). As expected, the reaction could
not be carried out without an electric current (Table 1, entry
20).
Table 1. Optimization of Reaction Conditions
b
entry
variation from standard conditions
yield (%)
c
1
2
3
4
standard conditions
CF3SO2Na (2.0 equiv)
MnBr2 (0.20 equiv)
MnBr2 (0.05 equiv)
1.0 mA
80 (61)
62
60
30
23
78
72
33
10
42
6
0
trace
0
20
50
40
14%
trace
With the optimized reaction conditions in hand, we then
explored the substrate scope of this electrochemical trifluor-
omethylation of diverse types of glycals with CF3SO2Na (Table
2). The 3,4-dideoxy-glycals 1b−d with different functional
5
6
3.0 mA
7
50 °C
a b
,
8
r.t.
Table 2. Substrate Scope of Glycals
9
C(+)/C(−)
10
11
12
13
14
15
16
17
18
19
20
C(+)/Pt(−)
Pt(+)/C(−)
ClCH2CH2Cl instead of CH3CN
1,2-dimethoxyethane instead of CH3CN
CH3CN/H2O (3:1) instead of CH3CN
Bu4NOTf instead of Bu4NClO4
Bu4NPF6 instead of Bu4NClO4
Me4NClO4 instead of Bu4NClO4
without MnBr2
air
without current
no reaction
a
Reaction conditions: 1a (0.05 mmol), CF3SO2Na (0.15 mmol, 3.0
equiv), MnBr2 (0.005 mmol, 0.1 equiv), Bu4NClO4(0.10 mmol, 2.0
equiv), and dry CH3CN (4.0 mL) in an undivided cell with Pt as the
anode and cathode, constant current = 2.0 mA, 75 °C, under an argon
b
c
atmosphere, 4 h. Yield of the isolated product. Reaction conditions:
1a (0.25 mmol), CF3SO2Na (0.75 mmol, 3.0 equiv), MnBr2 (0.025
mmol, 0.1 equiv), Bu4NClO4 (0.50 mmol, 2.0 equiv), and dry
CH3CN (20.0 mL) in an undivided cell with Pt as the anode and
cathode, constant current = 2.0 mA, 75 °C, under an argon
atmosphere, 4 h.
a
Reaction conditions: glycals 1b−p (0.05 mmol), CF3SO2Na (0.15
mmol, 3.0 equiv), MnBr2 (0.005 mmol, 0.1 equiv), Bu4NClO4 (0.10
mmol, 2.0 equiv), and dry CH3CN (4.0 mL) in an undivided cell with
Pt as the anode and cathode, constant current = 2.0 mA, 75 °C, under
an argon atmosphere, 4−6 h. Yield of the isolated product. Reaction
conditions: 1d (0.50 mmol), CF3SO2Na (1.50 mmol, 3.0 equiv),
MnBr2 (0.025 mmol, 0.05 equiv), Bu4NClO4 (1.00 mmol, 2.0 equiv),
and dry CH3CN (10.0 mL) in an undivided cell with Pt as the anode
and cathode, constant current = 2.0 mA, 75 °C, under an argon
atmosphere, 6 h.
S1). Unfortunately, no desired 2-trifluoromethyl-substituted
glucal 3a was obtained (Table S1, entry 1). With Bu4NBr18 as
the additive, the reaction could proceed, albeit in a very low yield
(Table S1, entry 2). When the temperature was raised to 75 °C,
the yield increased slightly (Table S1, entry 3). To our delight,
b
c
19
using MnCl2 instead of Bu4NBr, a 40% isolated yield of the
desired product 3a was observed (Table S1, entry 4). Replacing
MnCl2 with MnBr2,20 an increased yield was obtained (Table 1,
entry 2; Table S1, entry 5). The yield could be elevated to 80%
when the amount of CF3SO2Na was increased to 3.0 equiv
(Table 1, entry 1). However, the yield could not be improved
whether the equivalent of MnBr2 was increased or decreased
(Table 1, entries 3 and 4). Moreover, the similar reaction
efficiency was achieved by increasing the electric current to 3.0
mA or reducing the reaction temperature to 50 °C (Table 1,
entries 6 and 7), whereas either the reduced electric current or
room temperature led to low conversion (Table 1, entries 5 and
8). Besides, changing the electrode materials resulted in a
noticeable loss in yield (Table 1, entries 9−11). Further
experiments showed that the reaction outcome was significantly
influenced by the solvent. Only a trace amount of product 3a was
isolated when CH3CN was replaced with 1,2-dimethoxyethane,
whereas when ClCH2CH2Cl or CH3CN/H2O (3:1) was
employed, no desired product 3a was detected (Table 1, entries
groups were investigated. Both 3,4-dideoxyglycals with electron-
withdrawing (acetyl, benzoyl) and electron-donating (benzyl)
groups could be successfully converted to the desired
trifluoromethylated products 3b−d in good yields in this
electrochemical oxidative process. Similarly, the treatment of
benzylated galactal 1e led to 2-trifluoromethyl galactal 3e in an
excellent yield (90%). Notably, galactals 1f−g with acid-
sensitive protecting groups such as p-methoxybenzyl (PMB)
and tert-butyldimethylsilyl (TBS) also furnished the corre-
sponding products 3f−g in moderate to good yields under the
standard conditions. However, product 3h was obtained in only
30% yield when peracetylated galactal 1h was used as the
substrate, which might be attributed to the effect of the three
electron-withdrawing acetyl groups. In addition, p-methoxy-
benzylated and tert-butyldimethylsilylated D-glucals delivered
the desired products 3i−j in 68−75% yields. Furthermore, the
B
https://doi.org/10.1021/acs.joc.1c01318
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benzylated L-rhamnal/L-arabinal/D-xylal and p-methoxybenzy-
lated L-rhamnal/L-arabinal were suitable substrates in this
electrochemical transformation, affording the corresponding
products 3k−o in 64−75% yields. To our delight, the conversion
of benzylated lactal 1p was also realized in good yield (70%).
To explore the reaction mechanism of the electro-oxidative
trifluoromethylation, radical trapping experiments were carried
out. After the addition of 3.0 equiv of radical scavengers such as
2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) and 1,1-diphe-
nylethylene, the conversion was almost completely suppressed,
and no desired product 3e was obtained. Meanwhile, the
trapping product 4 was detected by GC−MS (Scheme 2, Figure
S2), implying that the reaction might involve a radical
mechanism.
peak at 1.41 V (vs Ag/AgCl), along with an obvious catalytic
current, which could be attributed to the MnBr2 redox couple of
the CF3SO2Na-bound complex (Figure 1, red curve).
Based on the results of control experiments and cyclic
voltammetry experiments, a plausible reaction mechanism for
the electrochemical trifluoromethylation was illustrated in
Scheme 3. MnII was first oxidized to MnIII at the anode. The
Scheme 3. Plausible Reaction Mechanism for the
Electrochemical Trifluoromethylation
Scheme 2. Radical Trapping Experiments
Finally, cyclic voltammetry (CV) experiments were con-
ducted to investigate the reaction mechanism. As shown in
Figure 1, the obvious oxidation peaks of the redox mediator,
CF3 radical was produced from CF3SO2Na by the MnIII-
mediated oxidation via a single -electron transfer (SET)
process.21 The attack of the CF3 radical onto the double bond
of glucal 1a provided radical intermediate II, which could be
further oxidized and transformed to glycosyl oxocarbenium ion
III on the surface of an anode. Subsequently, the deprotonation
of intermediate III afforded the desired trifluoromethylated
product 3a. H+ could be correspondingly reduced to release H2
on the surface of the cathode.
In summary, an efficient protocol has been developed for the
electrochemical trifluoromethylation of a wide range of glycals
with different protective groups in a regioselective manner by
using inexpensive, easily available, and bench-stable CF3SO2Na
as the trifluoromethyl source and a catalytic amount of MnBr2 as
the redox mediator. Mechanistic studies have revealed that the
CF3 radical might come from CF3SO2Na via the MnII-mediated
oxidation process. We anticipate that this novel approach will
not only enrich the methods for trifluoromethylation
modification of carbohydrates but also promote the discovery
of carbohydrate-related drugs.
Figure 1. Cyclic voltammetry of CF3SO2Na, MnBr2, and the mixture of
MnBr2 and CF3SO2Na. Conditions: A glassy carbon disk electrode
(diameter is 3.0 mm, PTFE shroud) used as a working electrode, a
platinum wire used as a counter electrode, Ag/AgCl electrode (3.5 M
KCl solution) used as a reference electrode, Bu4NClO4 (0.10 M in
MeCN), under an argon atmosphere, cyclic voltammogram at 0.05 V/s
with MnBr2 (2 mM), CF3SO2Na (8 mM) or MnBr2 (2 mM), and
CF3SO2Na (8 mM).
EXPERIMENTAL SECTION
■
General Information. Unless otherwise noted, all reagents were
purchased from commercial suppliers and were used directly without
further purification. CH2Cl2 and CH3CN were distilled over calcium
hydride prior to use. Reactions were monitored by thin-layer
chromatography (TLC). Spots were visualized with a solution of
concentrated sulfuric acid (5 mL) in CH3CH2OH (95 mL) or a
solution of (NH4)6Mo7O24·4H2O (12.00 g, 9.7 mmol) and Ce-
(NH4)2(NO3)6 (0.25 g, 0.45 mmol) in sulfuric acid (5%, 250 mL).
Flash column chromatography was carried out on silica gel (300−400
MnBr2, were recorded at 0.84 and 1.22 V (vs Ag/AgCl) (Figure
1, blue curve), which could be attributed to the direct oxidation
of MnII and the bromide ion (Br−).20 CF3SO2Na showed a
higher oxidation potential than that of MnBr2 (1.31 V vs 0.84
and 1.22 V, Figure 1, green curve), indicating MnBr2 is more
easily to be oxidized at the anode. Furthermore, the CV of the
mixture of MnBr2 and CF3SO2Na exhibited a new oxidation
1
mesh). H, 19F, and 13C NMR spectra were recorded in CDCl3 on a
Bruker AV 400 (400 MHz) or Bruker AV 600 (600 MHz) at room
temperature. The following abbreviations are used to indicate
multiplicity: s = singlet, d = doublet, t = triplet, q = quartet, m =
C
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Note
multiplet, dd = doublet of doublets, and br = broad. High-resolution
mass spectra data were recorded on a Waters Xevo G2 Q-TOF mass
spectrometer. Pt electrodes were purchased from Xuzhou Xinke
Instrument Corp. The potentiostats were purchased from Taobao.com,
HYELEC 3005B. Cyclic voltammetry was conducted in Metronm
Autolab. Compounds 1a and 1h are commercially available.
Compounds 1e, 1f, 1l, and 1m were synthesized according to the
reported literature.22
3,4,6-Tri-O-(p-methoxybenzyl)-D-glucal (1i). To a solution of the
commercially available 3,4,6-tri-O-acetyl-D-glucal (1.0 g, 3.67 mmol) in
CH3OH (20.0 mL) was added CH3ONa (20.0 mg, 0.37 mmol) slowly
at 0 °C. The reaction mixture was stirred at room temperature for 1 h
and evaporated in vacuo. Then the residue was dissolved in dry DMF
(20.0 mL), and NaH (880.8 mg, 22.02 mmol, 60%) and PMBCl (2.2
mL, 16.51 mmol) were successively added at 0 °C. The reaction
mixture was stirred at room temperature for 5 h. After completion, the
mixture was quenched with CH3OH at 0 °C, diluted with ethyl acetate,
washed with saturated aqueous NH4Cl, saturated aqueous NaHCO3,
and saturated aqueous NaCl, dried over anhydrous Na2SO4, and
evaporated in vacuo. The residue was purified by flash column
chromatography to give compound 1i as a yellow oil (eluent: petroleum
ether/ethyl acetate = 8:1 (v/v); 1.3 g, 72% yield). 1H NMR (400 MHz,
CDCl3): δ 7.29−7.26 (m, 4H), 7.18−7.15 (m, 2H), 6.90−6.83 (m,
6H), 6.43 (dd, J = 6.1, 1.1 Hz, 1H), 4.86 (dd, J = 6.1, 2.6 Hz, 1H), 4.76
(d, J = 10.9 Hz, 1H), 4.63−4.49 (m, 5H), 4.19 (dd, J = 4.3, 1.9 Hz, 1H),
4.06−4.01 (m, 1H), 3.83 (s, 3H), 3.82 (s, 6H), 3.82−3.73 (m, 3H).
The 1H NMR data for 1i coincide with the reported data.24
Preparation of Glycals. 2-Acetoxymethyl-3,4-dihydro-2H-pyran
(1b). To a solution of the commercially available 2-hydroxymethyl-3,4-
dihydro-2H-pyran (1.0 g, 8.77 mmol) in dry pyridine (8.0 mL) was
added acetic anhydride (1.23 mL, 13.16 mmol) at 0 °C slowly. The
reaction mixture was stirred at room temperature for 3 h. The mixture
was diluted with ethyl acetate, washed with water, saturated aqueous
NH4Cl, saturated aqueous NaHCO3, and saturated aqueous NaCl,
dried over anhydrous Na2SO4, and evaporated in vacuo. The residue
was purified by flash column chromatography to give compound 1b as a
yellow oil (eluent: petroleum ether/ethyl acetate = 10:1 (v/v); 1.2 g,
85% yield). 1H NMR (400 MHz, CDCl3): δ 6.39 (d, J = 6.1 Hz, 1H),
4.74−4.70 (m, 1H), 4.24−4.12 (m, 2H), 4.08−4.01 (m, 1H), 2.18−
2.07 (m, 4H), 2.05−1.95 (m, 1H), 1.89−1.81 (m, 1H), 1.75−1.63 (m,
1H). The 1H NMR data for 1b coincide with the reported data.23
2-Benzyloxymethyl-3,4-dihydro-2H-pyran (1c). To a solution of
the commercially available 2-hydroxymethyl-3,4-dihydro-2H-pyran
(1.0 g, 8.77 mmol) in dry DMF (10.0 mL) were added NaH (701.6
mg, 17.54 mmol, 60%) and BnBr (1.5 mL, 13.15 mmol) at 0 °C slowly.
The reaction mixture was stirred at room temperature for 5 h. After
completion, the mixture was quenched with CH3OH at 0 °C, diluted
with ethyl acetate, washed with saturated aqueous NH4Cl, saturated
aqueous NaHCO3, and saturated aqueous NaCl, dried over anhydrous
Na2SO4, and evaporated in vacuo. The residue was purified by flash
column chromatography to give compound 1c as a yellow oil (eluent:
petroleum ether/ethyl acetate = 10:1 (v/v); 1.6 g, 90% yield). 1H NMR
(400 MHz, CDCl3): δ 7.39−7.27 (m, 5H), 6.40 (d, J = 6.2 Hz, 1H),
4.71−4.65 (m, 1H), 4.64−4.55 (m, 2H), 4.06−3.99 (m, 1H), 3.59 (dd,
J = 10.2, 6.3 Hz, 1H), 3.52 (dd, J = 10.2, 4.3 Hz, 1H), 2.15−2.04 (m,
1H), 2.01−1.91 (m, 1H), 1.89−1.81 (m, 1H), 1.74−1.64 (m, 1H). The
1H NMR data for 1c coincide with the reported data.24
3,4,6-Tri-O-tert-butyldimethylsilyl-D-glucal (1j). Following the
procedure for the synthesis of compound 1g, compound 1j was
obtained starting from commercially available 3,4,6-tri-O-acetyl-D-
glucal (2.0 g, 7.34 mmol) as a yellow oil (eluent: petroleum ether/ethyl
acetate = 30:1 (v/v); 2.3 g, 65% yield). 1H NMR (400 MHz, CDCl3): δ
6.32 (d, J = 6.3 Hz, 1H), 4.72−4.67 (m, 1H), 4.02−3.97 (m, 1H),
3.96−3.86 (m, 2H), 3.81−3.72 (m, 2H), 0.90 (s, 9H), 0.888 (s, 9H),
0.887 (s, 9H), 0.10 (s, 6H), 0.079 (s, 3H), 0.076 (s, 3H), 0.06 (s, 3H),
1
0.05 (s, 3H). The H NMR data for 1j coincide with the reported
data.25
3,4-Di-O-benzyl-L-rhamnal (1k). Following the procedure for the
synthesis of compound 1c, compound 1k was obtained starting from L-
rhamnal (477.1 mg, 3.67 mmol) as a yellow oil (eluent: petroleum
ether/ethyl acetate = 8:1 (v/v); 967.0 mg, 85% yield). 1H NMR (400
MHz, CDCl3): δ 7.37−7.27 (m, 10H), 6.36 (dd, J = 6.2, 1.4 Hz, 1H),
4.90−4.81 (m, 2H), 4.73−4.64 (m, 2H), 4.57 (d, J = 11.7 Hz, 1H),
4.23−4.18 (m, 1H), 4.02−3.90 (m, 1H), 3.49 (dd, J = 9.0, 6.5 Hz, 1H),
1.38 (d, J = 6.4 Hz, 3H). The 1H NMR data for 1k coincide with the
reported data.26
2-Benzoylmethyl-3,4-dihydro-2H-pyran (1d). To a solution of the
commercially available 2-hydroxymethyl-3,4-dihydro-2H-pyran (1.0 g,
8.77 mmol) in dry pyridine (8.0 mL) was added BzCl (1.53 mL, 13.15
mmol) at 0 °C slowly. The reaction mixture was stirred at room
temperature for 3 h. After completion, the mixture was quenched with
CH3OH at 0 °C, diluted with ethyl acetate, washed with 1 M HCl
solution, saturated aqueous NaHCO3, and saturated aqueous NaCl,
dried over anhydrous Na2SO4, and evaporated in vacuo. The residue
was purified by flash column chromatography to give compound 1d as a
yellow oil (eluent: petroleum ether/ethyl acetate = 8:1 (v/v); 1.6 g,
83% yield). 1H NMR (400 MHz, CDCl3): δ 8.11−8.03 (m, 2H), 7.60−
7.54 (m, 1H), 7.47−7.42 (m, 2H), 6.40 (d, J = 6.2 Hz, 1H), 4.75−4.71
(m, 1H), 4.43 (d, J = 5.2 Hz, 2H), 4.22−4.13 (m, 1H), 2.20−2.10 (m,
1H), 2.10−2.00 (m, 1H), 1.98−1.90 (m, 1H), 1.86−1.74 (m, 1H). The
1H NMR data for 1d coincide with the reported data.24
3,4,6-Tri-O-tert-butyldimethylsilyl-D-galactal (1g). To a solution
of the commercially available 3,4,6-tri-O-acetyl-D-galactal (2.0 g, 7.34
mmol) in CH3OH (40.0 mL) was added CH3ONa (40.0 mg, 0.74
mmol) slowly at 0 °C. The reaction mixture was stirred at room
temperature for 1 h and evaporated in vacuo. Then the residue was
dissolved in dry DMF (15.0 mL), imidazole (3.0 g, 43.92 mmol), and
TBSCl (5.0 g, 33.03 mmol) were successively added at 0 °C. The
reaction mixture was stirred at room temperature for 5 h. After
completion, the mixture was quenched with H2O, diluted with ethyl
acetate, washed with saturated aqueous NaCl, dried over anhydrous
Na2SO4, and evaporated in vacuo. The residue was purified by flash
column chromatography to give compound 1g as a yellow oil (eluent:
petroleum ether/ethyl acetate = 30:1 (v/v); 2.5 g, 70% yield). 1H NMR
(400 MHz, CDCl3): δ 6.24 (d, J = 6.1 Hz, 1H), 4.72−4.63 (m, 1H),
4.12−4.04 (m, 4H), 3.88 (d, J = 8.1 Hz, 1H), 0.93 (s, 9H), 0.92 (s,
18H), 0.122 (s, 3H), 0.118 (s, 3H), 0.09 (s, 6H), 0.08 (s, 6H). The 1H
NMR data for 1g coincide with the reported data.25
3,4-Di-O-(p-methoxybenzyl)-L-arabinal (1n). Following the proce-
dure for the synthesis of compound 1i, compound 1n was obtained
starting from 3,4-di-O-acetyl-L-arabinal (928.6 mg, 4.64 mmol) as a
yellow oil (eluent: petroleum ether/ethyl acetate = 9:1 (v/v); 1.1 g,
80% yield). 1H NMR (400 MHz, CDCl3): δ 7.35−7.26 (m, 4H), 6.95−
6.86 (m, 4H), 6.41 (d, J = 6.0 Hz, 1H), 4.89−4.83 (m, 1H), 4.66 (s,
2H), 4.63 (d, J = 11.8 Hz, 1H), 4.54 (d, J = 11.8 Hz, 1H), 4.07−3.93 (m,
3H), 3.833 (s, 3H), 3.829 (s, 3H), 3.76−3.71 (m, 1H). The 1H NMR
data for 1n coincide with the reported data.15b
3,4-Di-O-benzyl-D-xylal (1o). Following the procedure for the
synthesis of compound 1c, compound 1o was obtained starting from D-
xylal (425.5 mg, 3.67 mmol) as a yellow oil (eluent: petroleum ether/
ethyl acetate = 8:1 (v/v); 956.0 mg, 88% yield). 1H NMR (400 MHz,
CDCl3): δ 7.40−7.27 (m, 10H), 6.55 (d, J = 6.2 Hz, 1H), 4.95−4.91
(m, 1H), 4.70−4.50 (m, 4H), 4.14−4.08 (m, 1H), 3.96 (dd, J = 11.7,
1.9 Hz, 1H), 3.84 (t, J = 3.4 Hz, 1H), 3.67 (t, J = 3.3 Hz, 1H). The 1H
NMR data for 1o coincide with the reported data.15b
2,3,3′,4,6,6′-Hexa-O-benzyl-D-lactal (1p). To a solution of the
commercially available D-lactose (10.0 g, 29.24 mmol) in dry pyridine
(60 mL) was added acetic anhydride (43.9 mL, 0.47 mol) at 0 °C
slowly. The reaction mixture was stirred at room temperature for 5 h.
After completion, the mixture was diluted with ethyl acetate, washed
with water, 1 M HCl solution, saturated aqueous NaHCO3, and
saturated aqueous NaCl, dried over anhydrous Na2SO4, and evaporated
in vacuo. The residue was dissolved in dry CH2Cl2 (50.0 mL), and 33%
HBr/HOAc (30 mL) was added at 0 °C slowly. The reaction mixture
was stirred at room temperature for 2 h, diluted with CH2Cl2, washed
with water, saturated aqueous NaHCO3, and saturated aqueous NaCl,
dried over anhydrous Na2SO4, and evaporated in vacuo. The residue
was dissolved in acetone (20.0 mL), and then NaH2PO4 (41.3 g, 0.28
mol) and Zn dust (13.1 g, 0.20 mol) were added. The reaction mixture
was stirred at room temperature for 10 min, and H2O (8.0 mL) was
D
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added. The reaction mixture was stirred at room temperature for 6 h.
After completion, the mixture was quenched with H2O and extracted
with ethyl acetate. The organic layers were combined, washed with
water, dried over anhydrous Na2SO4, and evaporated in vacuo. The
residue was purified by flash column chromatography to give
2,3,3′,4,6,6′-hexa-O-acetyl-D-lactal as a yellow oil (eluent: petroleum
ether/ethyl acetate = 4:1 (v/v); 11.1 g, 68% yield). 2,3,3′,4,6,6′-Hexa-
O-acetyl-D-lactal (5.0 g, 8.9 mmol) was dissolved in CH3OH (40.0 mL),
and CH3ONa (48.06 mg, 0.89 mmol) was added slowly at 0 °C. The
reaction mixture was stirred at room temperature for 1 h and
evaporated in vacuo. Then the residue was dissolved in dry DMF
(50.0 mL), and NaH (5.7 g, 0.14 mol, 60%) and BnBr (12.7 mL, 0.10
mol) were successively added at 0 °C. The reaction mixture was stirred
at room temperature for 5 h. After completion, the mixture was
quenched with CH3OH at 0 °C, diluted with ethyl acetate, washed with
saturated aqueous NH4Cl, saturated aqueous NaHCO3, and saturated
aqueous NaCl, dried over anhydrous Na2SO4, and evaporated in vacuo.
The residue was purified by flash column chromatography to give
compound 1p as a yellow oil (eluent: petroleum ether/ethyl acetate =
8:1 (v/v); 6.7 g, 89% yield). 1H NMR (400 MHz, CDCl3): δ 7.37−7.19
(m, 30H), 6.43 (d, J = 6.3 Hz, 1H), 4.93 (d, J = 11.6 Hz, 1H), 4.87 (dd, J
= 6.1, 3.6 Hz, 1H), 4.83 (d, J = 10.8 Hz, 1H), 4.75−4.66 (m, 3H), 4.62−
4.53 (m, 4H), 4.47 (s, 2H), 4.37 (d, J = 11.8 Hz, 1H), 4.32 (d, J = 11.7
Hz, 1H), 4.26 (dd, J = 9.2, 5.5 Hz, 1H), 4.17−4.10 (m, 2H), 3.89−3.74
(m, 3H), 3.67 (dd, J = 10.7, 3.5 Hz, 1H), 3.58−3.41 (m, 4H). 13C{1H}
NMR (101 MHz, CDCl3): δ 144.5, 138.80, 138.75, 138.7, 138.5, 138.1,
137.9, 128.41, 128.36, 128.31, 128.25, 128.22, 128.18, 127.9, 127.8,
127.7, 127.6, 127.5, 127.3, 102.9, 99.8, 82.3, 79.5, 75.9, 75.2, 74.6, 73.6,
73.53, 73.49, 73.3, 73.2, 73.0, 72.3, 70.4, 68.6, 68.0. HRMS (ESI): m/z
[M + NH4]+ calcd for C54H60NO9, 866.4263; found, 866.4282.
Electrochemical Trifluoromethylation. General Procedure A.
An oven-dried three-neck flask fitted with a stir bar was charged with
glycal (0.05 mmol), NaSO2CF3 (23.4 mg, 0.15 mmol), Bu4NClO4
(34.2 mg, 0.10 mmol), MnBr2 (1.0 mg, 0.005 mmol), and dry CH3CN
(4.0 mL). The flask was equipped with two platinum electrodes (2.0 ×
1.5 × 0.01 cm3). Then the reaction flask was sealed, degassed, and filled
with argon. The electrolysis was conducted at 75 °C under an argon
atmosphere with a constant current of 2.0 mA for 4−6 h. After
completion, the reaction mixture was concentrated in vacuo and eluted
by flash column chromatography with petroleum ether/ethyl acetate to
give the desired product.
Hz, 1H), 3.77 (dd, J = 10.4, 6.9 Hz, 1H), 3.66 (dd, J = 10.5, 5.1 Hz, 1H).
The 1H NMR data for 3a coincide with the reported data.27
2-Acetoxymethyl-5-trifluoromethyl-3,4-dihydro-2H-pyran (3b).
According to the general procedure A of the electrochemical
trifluoromethylation, compound 3b was obtained as a yellow oil (9.9
mg, 88%) after flash column chromatography (petroleum ether/ethyl
acetate = 10:1, v/v). 1H NMR (400 MHz, CDCl3): δ 6.99 (d, J = 1.3 Hz,
1H), 4.25 (dd, J = 11.8, 3.7 Hz, 1H), 4.18 (dd, J = 11.8, 6.3 Hz, 1H),
4.13−4.07 (m, 1H), 2.26−2.19 (m, 2H), 2.11 (s, 3H), 2.02−1.93 (m,
1H), 1.79−1.67 (m, 1H). The 1H NMR data for 3b coincide with the
reported data.15b
2-Benzyloxymethyl-5-trifluoromethyl-3,4-dihydro-2H-pyran (3c).
According to the general procedure A of the electrochemical
trifluoromethylation, compound 3c was obtained as a yellow oil (10.7
mg, 79%) after flash column chromatography (petroleum ether/ethyl
1
acetate = 15:1, v/v). H NMR (400 MHz, CDCl3): δ 7.39−7.27 (m,
5H), 6.99 (d, J = 1.2 Hz, 1H), 4.64−4.53 (m, 2H), 4.09−4.04 (m, 1H),
3.64−3.55 (m, 2H), 2.23−2.13 (m, 2H), 2.02−1.92 (m, 1H), 1.82−
1
1.68 (m, 1H). The H NMR data for 3c coincide with the reported
data.15b
2-Benzoylmethyl-5-trifluoromethyl-3,4-dihydro-2H-pyran (3d).
According to the general procedure A of the electrochemical
trifluoromethylation, compound 3d was obtained as a yellow oil
(10.2 mg, 71%) after flash column chromatography (petroleum ether/
ethyl acetate = 8:1, v/v). According to the general procedure C of the
electrochemical trifluoromethylation, compound 3d was obtained as a
yellow oil (84.4 mg, 59%) after flash column chromatography
(petroleum ether/ethyl acetate = 8:1, v/v). 1H NMR (400 MHz,
CDCl3): δ 8.11−8.01 (m, 2H), 7.59 (t, J = 8.0 Hz, 1H), 7.46 (t, J = 7.7
Hz, 2H), 7.02 (d, J = 0.5 Hz, 1H), 4.53−4.41 (m, 2H), 4.33−4.16 (m,
1H), 2.29−2.25 (m, 2H), 2.06−2.05 (m, 1H), 1.91−1.76 (m, 1H). The
1H NMR data for 3d coincide with the reported data.15b
2-Trifluoromethyl-3,4,6-tri-O-benzyl-D-galactal (3e). According to
the general procedure A of the electrochemical trifluoromethylation,
compound 3e was obtained as a yellow oil (21.8 mg, 90%) after flash
column chromatography (petroleum ether/ethyl acetate = 15:1, v/v).
1H NMR (400 MHz, CDCl3): δ 7.36−7.26 (m, 15H), 6.93 (s, 1H),
4.78−4.73 (m, 2H), 4.68−4.52 (m, 3H), 4.49−4.42 (m, 2H), 4.30 (d, J
= 3.0 Hz, 1H), 3.96−3.90 (m, 2H), 3.83 (dd, J = 11.3, 2.9 Hz, 1H). The
1H NMR data for 3e coincide with the reported data.27
2-Trifluoromethyl-3,4,6-tri-O-(p-methoxybenzyl)-D-galactal (3f).
According to the general procedure A of the electrochemical
trifluoromethylation, compound 3f was obtained as a yellow oil (20.1
mg, 70%) after flash column chromatography (petroleum ether/ethyl
acetate = 10:1, v/v). 1H NMR (400 MHz, CDCl3): δ 7.24−7.18 (m,
6H), 6.90 (d, J = 1.0 Hz, 1H), 6.89−6.83 (m, 6H), 4.68 (dd, J = 11.1, 6.0
Hz, 2H), 4.59−4.45 (m, 3H), 4.42−4.37 (m, 1H), 4.35 (d, J = 11.5 Hz,
1H), 4.25 (d, J = 3.2 Hz, 1H), 3.89 (t, J = 3.9 Hz, 1H), 3.85 (dd, J = 10.9,
8.6 Hz, 1H), 3.81 (s, 9H), 3.76 (dd, J = 11.2, 3.1 Hz, 1H). The 1H NMR
data for 3f coincide with the reported data.15b
General Procedure B. An oven-dried three-neck flask fitted with a
stir bar was charged with glycal (0.25 mmol), NaSO2CF3 (117.0 mg,
0.75 mmol), Bu4NClO4 (171.0 mg, 0.50 mmol), MnBr2 (5.0 mg, 0.025
mmol), and dry CH3CN (20.0 mL). The flask was equipped with two
platinum electrodes (2.0 × 1.5 × 0.01 cm3). Then the reaction flask was
sealed, degassed, and filled with argon. The electrolysis was conducted
at 75 °C under an argon atmosphere with a constant current of 2.0 mA
for 4 h. After completion, the reaction mixture was concentrated in
vacuo and eluted by flash column chromatography with petroleum
ether/ethyl acetate to give the desired product.
2-Trifluoromethyl-3,4,6-tri-O-tert-butyldimethylsilyl-D-galactal
(3g). According to the general procedure A of the electrochemical
trifluoromethylation, compound 3g was obtained as a yellow oil (23.6
mg, 85%) after flash column chromatography (petroleum ether/ethyl
acetate = 60:1, v/v). 1H NMR (400 MHz, CDCl3): δ 6.89 (d, J = 1.4 Hz,
1H), 4.26−4.19 (m, 2H), 4.16−4.10 (m, 1H), 4.04−4.01 (m, 1H), 3.92
(d, J = 12.1 Hz, 1H), 0.94 (s, 9H), 0.89 (s, 9H), 0.88 (s, 9H), 0.153 (s,
3H), 0.151 (s, 3H), 0.11 (s, 6H), 0.054 (s, 3H), 0.052 (s, 3H). 19F NMR
(376 MHz, CDCl3): δ −61.28. 13C{1H} NMR (101 MHz, CDCl3): δ
147.1 (q, J = 7.0 Hz), 124.7 (q, J = 270.0 Hz), 106.1 (q, J = 30.4 Hz),
80.8, 69.6, 63.1, 60.9, 26.2, 26.0, 25.8, 18.5, 18.4, 18.2, −3.7, −4.2, −5.0,
−5.2, −5.3, −5.6. HRMS (ESI): m/z [M + H]+ calcd for
C25H52F3O4Si3, 557.3120; found, 557.3126.
General Procedure C. An oven-dried three-neck flask fitted with a
stir bar was charged with glycal (0.50 mmol), NaSO2CF3 (234.0 mg,
1.50 mmol), Bu4NClO4 (342.0 mg, 1.00 mmol), MnBr2 (5.0 mg, 0.025
mmol), and dry CH3CN (10.0 mL). The flask was equipped with two
platinum electrodes (2.0 × 1.5 × 0.01 cm3). Then the reaction flask was
sealed, degassed, and filled with argon. The electrolysis was conducted
at 75 °C under an argon atmosphere with a constant current of 2.0 mA
for 6 h. After completion, the reaction mixture was concentrated in
vacuo and eluted by flash column chromatography with petroleum
ether/ethyl acetate to give the desired product.
2-Trifluoromethyl-3,4,6-tri-O-benzyl-D-glucal (3a). According to
the general procedure A of the electrochemical trifluoromethylation,
compound 3a was obtained as a yellow oil (19.4 mg, 80%) after flash
column chromatography (petroleum ether/ethyl acetate = 15:1, v/v).
According to the general procedure B of the electrochemical
trifluoromethylation, compound 3a was obtained as a yellow oil (73.8
mg, 61%) after flash column chromatography (petroleum ether/ethyl
2-Trifluoromethyl-3,4,6-tri-O-acetyl-D-galactal (3h). According to
the general procedure A of the electrochemical trifluoromethylation,
compound 3h was obtained as a yellow oil (5.1 mg, 30%) after flash
column chromatography (petroleum ether/ethyl acetate = 20:1, v/v).
1H NMR (400 MHz, CDCl3): δ 7.09 (s, 1H), 5.84 (d, J = 5.0 Hz, 1H),
1
acetate = 15:1, v/v). H NMR (400 MHz, CDCl3): δ 7.44−7.14 (m,
15H), 7.06 (s, 1H), 4.57−4.43 (m, 7H), 4.09 (s, 1H), 3.89 (t, J = 3.2
5.45 (dd, J = 4.3, 3.1 Hz, 1H), 4.47−4.43 (m, 1H), 4.42−4.35 (m, 1H),
E
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Note
4.27 (dd, J = 11.8, 4.1 Hz, 1H), 2.12 (s, 3H), 2.10 (s, 3H), 2.07 (s, 3H).
The 1H NMR data for 3h coincide with the reported data.15b
2′-Trifluoromethyl-2,3,3′,4,6,6′-hexa-O-benzyl-D-lactal (3p). Ac-
cording to the general procedure A of the electrochemical
trifluoromethylation, compound 3p was obtained as a yellow oil
(32.1 mg, 70%) after flash column chromatography (petroleum ether/
2-Trifluoromethyl-3,4,6-tri-O-(p-methoxybenzyl)-D-glucal (3i).
According to the general procedure A of the electrochemical
trifluoromethylation, compound 3i was obtained as a yellow oil (21.5
mg, 75%) after flash column chromatography (petroleum ether/ethyl
1
ethyl acetate = 6:1, v/v). H NMR (400 MHz, CDCl3): δ 7.34−7.22
(m, 30H), 7.05 (d, J = 1.5 Hz, 1H), 4.93 (d, J = 11.7 Hz, 1H), 4.79 (d, J
= 10.8 Hz, 1H), 4.77−4.54 (m, 7H), 4.49−4.33 (m, 5H), 4.26 (s, 1H),
4.23 (t, J = 2.5 Hz, 1H), 3.86 (d, J = 2.9 Hz, 1H), 3.81−3.74 (m, 2H),
3.61 (dd, J = 10.5, 5.1 Hz, 1H), 3.54−3.42 (m, 4H). 19F NMR (376
MHz, CDCl3): δ −62.60. 13C{1H} NMR (151 MHz, CDCl3): δ 147.7
(q, J = 6.7 Hz), 138.5, 138.4, 137.78, 137.75, 128.5, 128.4, 128.32,
128.25, 127.9, 127.8, 127.73, 127.67, 127.64, 127.62, 127.5, 124.9 (q, J
= 270.3 Hz), 103.6 (q, J = 30.9 Hz), 102.8, 82.0, 79.0, 75.8, 75.2, 74.6,
73.7, 73.6, 73.5, 73.3, 73.2, 72.1, 70.9, 68.9, 68.8, 67.4. HRMS (ESI): m/
z [M + HCOO]− calcd for C56H56F3O11, 961.3780; found, 961.3771.
1
acetate = 10:1, v/v). H NMR (400 MHz, CDCl3): δ 7.21−7.13 (m,
6H), 7.03 (d, J = 1.5 Hz, 1H), 6.89−6.80 (m, 6H), 4.54−4.36 (m, 7H),
4.04 (d, J = 1.8 Hz, 1H), 3.83 (t, J = 3.4 Hz, 1H), 3.81 (s, 6H), 3.80 (s,
3H), 3.72 (dd, J = 10.5, 6.9 Hz, 1H), 3.61 (dd, J = 10.5, 5.0 Hz, 1H).
The 1H NMR data for 3i coincide with the reported data.15b
2-Trifluoromethyl-3,4,6-tri-O-tert-butyldimethylsilyl-D-glucal (3j).
According to the general procedure A of the electrochemical
trifluoromethylation, compound 3j was obtained as a yellow oil (18.9
mg, 68%) after flash column chromatography (petroleum ether/ethyl
acetate = 60:1, v/v). 1H NMR (400 MHz, CDCl3): δ 6.99 (d, J = 1.7 Hz,
1H), 4.22−4.18 (m, 1H), 4.01 (s, 1H), 3.96 (dd, J = 11.6, 8.2 Hz, 1H),
3.91−3.88 (m, 1H), 3.75 (dd, J = 11.6, 4.5 Hz, 1H), 0.90 (s, 9H), 0.87
(s, 9H), 0.86 (s, 9H), 0.11 (s, 3H), 0.09 (s, 9H), 0.06 (s, 3H), 0.05 (s,
3H). 19F NMR (376 MHz, CDCl3): δ −62.79. 13C{1H} NMR (151
MHz, CDCl3): δ 146.6 (q, J = 6.9 Hz), 125.3 (q, J = 264.2 Hz), 103.9
(q, J = 30.4 Hz), 81.4, 67.9, 63.3, 61.4, 25.9, 25.6, 25.5, 18.4, 17.83,
17.80, −4.2, −4.7, −5.2, −5.3, −5.6. HRMS (ESI): m/z [M + HCOO]−
calcd for C26H52F3O6Si3, 601.3029; found, 601.3030.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c01318.
■
sı
Copies of 1H, 19F and 13C{1H} NMR spectra of
compounds (PDF)
FAIR data, including the primary NMR FID files, for
compounds 1b−1d, 1g, 1i−1k, 1n−1p, and 3a−3p (ZIP)
2-Trifluoromethyl-3,4-di-O-benzyl-L-rhamnal (3k). According to
the general procedure A of the electrochemical trifluoromethylation,
compound 3k was obtained as a yellow oil (14.2 mg, 75%) after flash
column chromatography (petroleum ether/ethyl acetate = 10:1, v/v).
1H NMR (400 MHz, CDCl3): δ 7.39−7.27 (m, 10H), 7.02 (d, J = 1.2
Hz, 1H), 4.65−4.59 (m, 2H), 4.57−4.52 (m, 2H), 4.43−4.35 (m, 1H),
4.14 (d, J = 3.1 Hz, 1H), 3.60 (t, J = 3.7 Hz, 1H), 1.38 (d, J = 7.0 Hz,
3H). The 1H NMR data for 3k coincide with the reported data.15b
2-Trifluoromethyl-3,4-di-O-(p-methoxybenzyl)-L-rhamnal (3l).
According to the general procedure A of the electrochemical
trifluoromethylation, compound 3l was obtained as a yellow oil (14.0
mg, 64%) after flash column chromatography (petroleum ether/ethyl
AUTHOR INFORMATION
Corresponding Authors
■
De-Cai Xiong − State Key Laboratory of Natural and
Biomimetic Drugs, School of Pharmaceutical Sciences, Peking
University, Beijing 100191, China; State Key Laboratory of
Pharmaceutical Biotechnology, Nanjing University, Nanjing,
Jiangsu 210023, China; orcid.org/0000-0002-5187-
9313; Email: decai@bjmu.edu.cn
Xin-Shan Ye − State Key Laboratory of Natural and Biomimetic
Drugs, School of Pharmaceutical Sciences, Peking University,
Beijing 100191, China; orcid.org/0000-0003-4113-
506X; Email: xinshan@bjmu.edu.cn
1
acetate = 9:1, v/v). H NMR (400 MHz, CDCl3): δ 7.25−7.18 (m,
4H), 7.00 (d, J = 1.1 Hz, 1H), 6.91−6.84 (m, 4H), 4.58−4.53 (m, 2H),
4.50−4.46 (m, 2H), 4.38−4.29 (m, 1H), 4.11 (d, J = 3.2 Hz, 1H), 3.81
(s, 3H), 3.80 (s, 3H), 3.56 (t, J = 3.8 Hz, 1H), 1.36 (d, J = 6.9 Hz, 3H).
The 1H NMR data for 3l coincide with the reported data.15b
Authors
2-Trifluoromethyl-3,4-di-O-benzyl-L-arabinal (3m). According to
the general procedure A of the electrochemical trifluoromethylation,
compound 3m was obtained as a yellow oil (12.9 mg, 71%) after flash
column chromatography (petroleum ether/ethyl acetate = 10:1, v/v).
1H NMR (400 MHz, CDCl3): δ 7.39−7.27 (m, 10H), 6.97 (d, J = 1.5
Hz, 1H), 4.90 (d, J = 10.9 Hz, 1H), 4.75−4.61 (m, 3H), 4.30 (d, J = 2.3
Hz, 1H), 4.17−4.07 (m, 2H), 3.80−3.75 (m, 1H). The 1H NMR data
for 3m coincide with the reported data.15b
2-Trifluoromethyl-3,4-di-O-(p-methoxybenzyl)-L-arabinal (3n).
According to the general procedure A of the electrochemical
trifluoromethylation, compound 3n was obtained as a yellow oil
(15.5 mg, 73%) after flash column chromatography (petroleum ether/
ethyl acetate = 10:1, v/v). 1H NMR (400 MHz, CDCl3): δ 7.30−7.26
(m, 4H), 6.95 (d, J = 1.4 Hz, 1H), 6.92−6.84 (m, 4H), 4.82 (d, J = 10.5
Hz, 1H), 4.66−4.61 (m, 2H), 4.56 (d, J = 11.5 Hz, 1H), 4.25 (d, J = 2.2
Hz, 1H), 4.13−4.02 (m, 2H), 3.82 (s, 3H), 3.80 (s, 3H), 3.77−3.71 (m,
1H). The 1H NMR data for 3n coincide with the reported data.15b
2-Trifluoromethyl-3,4-di-O-benzyl-D-xylal (3o). According to the
general procedure A of the electrochemical trifluoromethylation,
compound 3o was obtained as a yellow oil (11.8 mg, 65%) after flash
column chromatography (petroleum ether/ethyl acetate = 15:1, v/v).
1H NMR (400 MHz, CDCl3): δ 7.39−7.27 (m, 10H), 7.16 (d, J = 1.4
Hz, 1H), 4.62−4.48 (m, 4H), 4.29−4.24 (m, 1H), 4.03−3.96 (m, 2H),
3.65−3.63 (m, 1H). 19F NMR (376 MHz, CDCl3): δ −62.77. 13C{1H}
NMR (101 MHz, CDCl3): δ 149.9 (q, J = 6.9 Hz), 137.5, 137.4, 128.6,
128.5, 128.11, 128.05, 127.8, 125.0 (q, J = 270.7 Hz), 103.5 (q, J = 31.1
Hz), 72.0, 71.1, 69.9, 66.4, 64.2. HRMS (ESI): m/z [M + NH4]+ calcd
for C20H23F3NO3, 382.1625; found, 382.1624.
Miao Liu − State Key Laboratory of Natural and Biomimetic
Drugs, School of Pharmaceutical Sciences, Peking University,
Beijing 100191, China
Zhao-Xiang Luo − State Key Laboratory of Natural and
Biomimetic Drugs, School of Pharmaceutical Sciences, Peking
University, Beijing 100191, China
Tian Li − State Key Laboratory of Natural and Biomimetic
Drugs, School of Pharmaceutical Sciences, Peking University,
Beijing 100191, China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c01318
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was financially supported by grants from the National
Natural Science Foundation of China (21772006 and
91853122), the National Key Research and Development
Program of China (2018YFA0507602), the Beijing Outstanding
Young Scientist Program (BJJWZYJH01201910001001), the
Open Fund of State Key Laboratory of Pharmaceutical
Biotechnology, Nanjing University, China (KF-GN-202106),
and the Fundamental Research Funds for the Central
Universities.
F
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Note
(12) Mei, H. B.; Pajkert, R.; Wang, L.; Li, Z. Y.; Roschenthaler, G. V.;
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(13) Hong, H. L.; Li, Y. B.; Chen, L.; Li, B.; Zhu, Z. Z.; Chen, X. W.;
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