Synthesis of C6 acetylenic alcohols

Article abstract of DOI:10.14233/ajchem.2015.17094

C₆ acetylenic alcohols are important intermediates in the synthesis of Vitamin A and carotenoids. New synthesis methods of the C₆ acetylenic alcohols and their four derivatives are reported. These designed synthesis methods are useful improvement to the present methodologies. Structures of these compounds are confirmed by ¹H NMR, IR and mass spectra analysis.

Full text of DOI:10.14233/ajchem.2015.17094

Asian Journal of Chemistry; Vol. 27, No. 2 (2015), 635-638
ASIAN JOURNAL OF CHEMISTRY
http://dx.doi.org/10.14233/ajchem.2015.17094
Synthesis of C6 Acetylenic Alcohols
*
SHUAI PU, AI GUI ZHANG, SHAO FENG ZHANG and YU LIANG WANG
College of Chemistry, Sichuan University, Chengdu 610064, P.R. China
*Corresponding author: Tel: +86 15378195811; E-mail: chemwang2008@163.com; 13980956073@163.com
Received: 21 January 2014; Accepted: 11 April 2014; Published online: 10 January 2015;
AJC-16635
C6 acetylenic alcohols are important intermediates in the synthesis of Vitamin A and carotenoids. New synthesis methods of the C6
acetylenic alcohols and their four derivatives are reported. These designed synthesis methods are useful improvement to the present
methodologies. Structures of these compounds are confirmed by 1H NMR, IR and mass spectra analysis.
Keywords: C6 acetylenic alcohols, Vitamin A, Carotenoids.
is extremely hazardous; 2) liquid ammonia as the solvent
requires extreme low temperatures in industry, which is costly
and energy-consuming; 3) metallic sodium or potassium used
for the preparation of metal acetylide is highly flammable and
difficult to handle industrially.
INTRODUCTION
C6 acetylenic alcohols and their derivatives 1 and 2 (Fig. 1)
are important intermediates in the synthesis of Vitamin A and
carotenoids which play key roles in many physiological proce-
sses such as vision, reproduction, immune competence, cell
differentiation and brain function1-3. Compound 1 and 2 (Fig. 1)
can be coupling with carbonyl compounds followed by a serial
of transformations to give Vitamin A4 and other carotenoids
such as zeaxanthix4, canthaxanthin5 and astaxanthin6,7. There-
fore, it is important to find a better way to prepare C6 acetylenic
alcohols and their derivatives in organic synthesis.
To avoid the prior disadvantages, we proposed herein
a new method for the synthesis of C6 acetylenic alcohols
(Scheme-I). In contrast to the current methods, this safe
alternative synthetic route has no requirement of hazardous
reagents and no extremely low temperatures.
O
O
a
b
OH
OTMS
4
3
c
d
OR
OR
OH
CH3
OH
CHO
,
,
,
Si(CH3)3
H
R
OH
CH(OEt)
O
5
6
2
1
2
Scheme-I: Synthetic route of C6 acetylenic alcohols compounds 2 and 5;
Reagents and conditions: (a) TMSCl, Et3N, CH2Cl2, 0-5, 2 h;
(b), [i] ethynylmagnesium bromide, THF, 0-5 °C; [ii] dilute HCl;
(c) [i] CrO3, pyridine, dichloromethane, 0-5 °C, 0.5 h; [ii] 20 %
H2SO4, EtOH, N2, 60 °C, 5-8 h; (d) NaBH4, EtOH, r.t., 1h
Fig. 1. Structures of C6 acetylenic alcohols compounds 1 and 2
The current methods to access C6 acetylenic alcohols are
based upon the ethynylation reactions of methyl vinyl ketone
with sodium acetylide at -55 °C in liquid ammonia8-11. Then the
ethynylation product 3-methylpent-1-en-4-yn-3-ol 1 (Fig. 1,
R = H) can smoothly isomerized with dilute sulphuric acid to
yield the primary alcohol, 3-methylpent-2-en-4-yn-1-ol 2
(Fig. 1, R = H). However, this method may cause three potential
safety hazards: 1) methyl vinyl ketone with lachrymatory effect
In order to develop new method for the synthesis of
VitaminA and carotenoids, we designed and synthesized four
acetylenic alcohol derivatives 7, 8, 10 and 11 (Scheme-II),
which shared the same characteristics of six-carbon backbones
bearing an alkynyl group. These four acetylenic alcohol

636 Pu et al.
Asian J. Chem.
OH), 2.49 (s, 1H, ethynyl), 1.96 (ddd, J = 14.4, 10.0 4.4 Hz, 1H),
1.79 (ddd, J = 14.5, 4.5, 3.6 Hz, 1H), 1.51 (s, 3H, CH3).
OTMS
a
OTMS
Synthesis of 3-methylpent-2-en-4-ynal (6): CrO3 (0.6
mol) was slowly added over pyridine (1.2 mol) in dry dichloro-
methane (150 mL). After 15-20 min, dry celite (20 g) was
added and then a solution of diol compound 5 (0.1 mol) in
dry dichloromethane (10 mL) was slowly added. When most
of the starting diol was consumed, the reaction mixture was
filtered through a pad of silica. The filtrate was treated with
hydroquinone (0.01 mol) and a solution of 20 % H2SO4
(30 mL) and EtOH (10 mL). The mixture was heated to distill
dichloromethane and then was heated for 7-8 h at 60 °C in
nitrogen atmosphere. When the reaction was completed, the
aqueous layer was extracted with diethyl ether (3 × 10 mL).
The combined organic layer was washed with brine, dried with
Na2SO4 and evaporated. The residue was distilled to afford a
pale yellow liquid. Yield 25 %, b.p. 44-47°C/5 mmHg (lit.17
58-60°C/10 mmHg); FT-IR (film) (cm-1): 3266, 2843, 2089,
1669, 1598, 1379, 1175; 1H NMR (400 MHz, CDCl3): δ (ppm)
= 10.04 (d, J = 8 Hz, 1H, CHO), 6.24 (dd, J = 8.2, 1.6 Hz, 1H,
C = CH), 3.58 (s, 1H, ethynyl), 2.15 (d, J = 1.6 Hz, 3H, CH3);
GC-MS: 94.
7
OH
OH
b
O
OEt
O
5
OEt
8
O
O
O
c
d
e
O
OEt
O
OEt
OH
OH
O
3
9
10
11
Scheme-II: Synthetic route of C6 acetylenic alcohol derivatives compounds
7, 8, 10 and 11; Reagents and conditions: (a) TMSCl, Et3N,
CH2Cl2, 0-5 °C, 10 h; (b) ethyl vinyl ether, pyridine, p-TsOH,
CH2Cl2, r.t., 12 h; (c) ethyl vinyl ether, pyridine, p-TsOH,
CH2Cl2, r.t., 3 h; (d) [i] ethynylmagnesium bromide, THF, 0-5
°C; [ii] saturated NH4Cl; (e) HCl (g), EtOH, r.t., 1.5 h
derivatives could be potentially utilized in the synthesis of
Vitamin A and carotenoids.
EXPERIMENTAL
Most of the chemical reagents used in this study were
acquired from commercial sources without further purification.
Solvents were purchased and dried using standard methods.
The IR spectra were recorded on a Perkin-Elemer 16PC-FT
spectrometer. HR-MS spectral were acquired with theAgilent
6210 (DOF-MAS) spectrometer (Agilent Inc., Santa Clara,
CA, USA) using the electrospray ionisation (ESI) method
and GC-MS spectral were recorded on an Agilent 6890N GC
connected to anAgilent 5975 mass selective detector. 1H NMR
spectra were recorded on a varian Unity Inova-400 spectro-
meter (Varian Inc., Palo Alto, CA, USA) with CDCl3 as the
solvent and tetramethylsilane (TMS) as the internal standard.
Spectral data of known compounds 412, 513, 614, 215 are in
accordance with previous reports.
Synthesis of 3-methylpent-2-en-4-yn-1-ol (2, R = H):
NaBH4 (31.3 mmol) was added in batches to a solution of
compound 6 (10.4 mmol) in ethanol (10 mL) at 25 °C. The
reaction mixture was stirred for 3 h at the same temperature.
The reaction was quenched with H2O and extracted with ethyl
acetate (3 × 5 mL). The solvent was evaporated and the residue
was distilled to afford colorless oil. The combined organic
layer was washed with brine, dried with Na2SO4 and concen-
trate in vacuo. The residue was purified by column chromato-
graphy on silica gel (petroleum ether/ethyl acetate = 10:1) to
afford a yellow oil. Yield 95 %, FT-IR (film) (cm-1): 3293,
1
2926, 2875, 2094, 1630, 1435, 1379, 1243, 1086, 1006; H
Synthesis of 4-(trimethylsilyloxy)butan-2-one (4):
Chlorotrimethylsilane (0.9 mol) was added dropwise to the
mixture of compound 3 (0.75 mol) and triethylamine (0.98
mol) in dry dichloromethane (300 mL) at 0-5 °C. After the
addition was completed, the reaction mixture was stirred at
room temperature for 2 h as required to complete the reaction
(monitored by TLC). The precipitated solid was filtered off
and washed with dichloromethane. The filtrate was condensed
in vacuo and then distilled to afford a colorless liquid. Yield
95 %, b.p. 52-54 °C/10 mmHg (lit.16 52 °C/10 mmHg); FT-IR
(film) (cm-1): 2955, 2896, 1713, 1358, 1248, 1175, 1101, 876,
840; 1H NMR (400 MHz, CDCl3): δ (ppm) = 3.84 [t, J = 6.4
Hz, 2H, CH2OSi(CH3)3], 2.63 (t, J = 6.4 Hz, 2H, COCH2),
2.16 (s, 3H, CH3CO), 0.10 [s, 9H, Si(CH3)3]; GC-MS: 160.
Synthesis of 3-methylpent-4-yne-1,3-diol (5):A solution
of compound 4 (0.375 mol) in THF (30 mL) was added
dropwise to ethynylmagnesium bromide14 (0.75 mol) at 0-5 °C
over a period of 1 h.After addition of compound 4 the reaction
mixture was hydrolyzed with 5 % HCl. The aqueous layer
was extracted with ethyl acetate (4 × 50 mL), the combined
extracts were dried Na2SO4 and evaporated and the residue
was distilled to afford a colorless oil. Yield 55 %, b.p. 76-78
°C/3 mmHg; FT-IR (film) (cm-1): 3369, 3294, 2933, 2110,
NMR (400 MHz, CDCl3): δ (ppm) = 5.95 (ddd, J = 6.7, 3.7,
0.7 Hz, 1H, C = CH), 4.33 (dd, J = 6.8, 0.8 Hz, 1H, CH2OH),
3.19 (s, 1H, ethynyl), 2.28 (s, 1H, OH), 1.90 (d, J = 1.2 Hz,
3H, CH3); GC-MS: 96.
Synthesis of 3,5-bis(trimethylsilyloxy)-3-methylpent-
1-yne (7): Chlorotrimethylsilane (0.12 mol) was added
dropwise to the mixture of compound 5 (0.05 mol) and
triethylamine (0.13 mol) in dry dichloromethane (40 mL) at
0-5 °C.After the addition was completed, the reaction mixture
was stirred at room temperature for 9 h as required to complete
the reaction (monitored by TLC). The precipitated solid was
filtered off and washed with dichloromethane. The filtrate was
condensed in vacuo and then distilled to afford a colorless
liquid. Yield 91 %, b.p. 64-68 °C/13 mmHg; FT-IR (film)
(cm-1): 3307, 2955, 2899, 2106, 1677, 1369, 1251, 1085, 837;
1H NMR (400 MHz, CDCl3): δ (ppm) = 3.81 [t, J = 6.8 Hz,
2H, -CH2OSi(CH3)3], 2.47 (s, 1H, ethynyl), 1.97-1.90 (m, 2H,
CH2), 0.19 [s, 9H, Si(CH3)3], 0.14 [s, 9H, Si(CH3)3]; HR-MS
(ESI): Calcd. for C12H26NaO2Si2 [M + Na]+: 281.1369, Found
281.1363.
Synthesis of 3,5-bis(1-ethoxyethoxy)-3-methylpent-1-
yne (8): p-Toluenesulfonic acid monohydrate (40 mmol) was
added to pyridine (43 mmol) with stirring in dichloromethane
(350 mL) at room temperature (slightly exothermic). After
1
1374; H NMR (400 MHz, CDCl3): δ (ppm) = 4.13 (td, J =
10.4, 3.2 Hz, 1H), 3.88 (dt, J = 11.2, 4.4 Hz, 1H), 3.77 (br s, 2H,

Vol. 27, No. 2 (2015)
Synthesis of C6 Acetylenic Alcohols 637
stirring for 0.5 h, a mixture of compound 5 (0.2 mol) and
ethyl vinyl ether (1.2 mol) was added.After reaction was stirred
at room temperature for 13 h, the reaction mixture was washed
with H2O (2 × 50 mL), brine (50 mL) and finally dried over
anhydrous Na2SO4. The crude product was purified by column
chromatography on silica gel (petroleum ether/ethyl acetate =
10:1) to afford a pale yellow liquid. Yield 95 %; FT-IR (film)
(cm-1): 3301, 2982, 2935, 2103, 1683, 1447, 1373, 1337, 1136,
1080, 959, 864; 1H NMR (400 MHz, CDCl3): δ (ppm) = 5.15-
5.09 (m, 1H, CHCH3), 4.69 (q, J = 5.2 Hz, 1H, CHCH3), 3.90-
3.96 (m, 4H), 3.56-3.45 (m, 2H), 2.50 (s, 1H, ethynyl), 2.13-
1.94 (m, 2H), 1.47 (s, 3H, CH3), 1.35-1.30 (m, 6H, CH3), 1.23-
1.17 (m, 6H, CH3); HR-MS (ESI): Calcd. for C14H26NaO4
[M + Na]+: 281.1729, found 281.1721.
CDCl3): δ (ppm) = 5.16 (q, J = 5.2 Hz, 1H, CHCH3), 4.08-
3.94 (m, 2H, CH2O), 2.54 (s, 1H, ethynyl), 1.89 (td, J = 12.8,
4.8 Hz, 1H), 1.59 (td, J = 13.2, 1.6 Hz, 1H), 1.53 (s, 3H, CH3),
1.31 (d, J = 5.2 Hz, 3H, CHCH3); GC-MS: 140.
RESULTS AND DISCUSSION
New synthetic method of C6 acetylenic alcohols: Previous
studies13 disclosed a costly procedure to access diol compound
5. Reaction of 3-acetyl-4-benzyloxazolidin-2-one with
3-butyn-2-one furnished aldol condensation product in the
presence of LDA at -78 °C and the condensation product was
reduced with LiBH4 to provide diol compound 5. Compared
with above reported method, present new synthetic route to
compound 5 is concise and the starting materials are commer-
cially available and inexpensive (Scheme-I). 4-Hydroxy-2-
butanone (3) was protected by chlorotrimethylsilane to give
silyl ether (4) in high yield at room temperature. After that,
compound 4 was ethynylated with ethynylmagnesium bromide
followed by easy deprotection of trimethylsiyl group with
dilute HCl to afford diol compound 5 in moderate yield at
room temperature.
Synthesis of 4-(1-ethoxyethoxy)butan-2-one (9):
p-Toluenesulfonic acid monohydrate (75 mmol) was added to
pyridine (82.5 mmol) with stirring in dichloromethane (400
mL) at room temperature (slightly exothermic). After stirring
for 0.5 h, a mixture of compound 3 (750 mmol) and ethyl
vinyl ether (1.5 mol) was added, followed by stirring for 6 h.
The reaction mixture was washed with H2O (2 × 40 mL), brine
(40 mL) and finally dried over anhydrous Na2SO4. The crude
product was purified by column chromatography on silica gel
(petroleum ether/ethyl acetate = 12:1) to afford a colorless
liquid. Yield 92 %; FT-IR (film) (cm-1): 3349, 2973, 2884,
1716, 1379, 1127, 1092, 1050, 947, 879; 1H NMR (400 MHz,
CDCl3): δ (ppm) = 4.68 (q, J = 4.4 Hz, 1H, CHCH3), 3.86-
3.81 (m, 1H), 3.72-3.60 (m, 2H), 3.49-3.44 (m, 1H), 2.68 (t,
J = 5.4 Hz, 2H, CH3COCH2), 2.19 (s, 3H, CH3CO), 1.29 (d,
J = 4.8 Hz, 3H, CHCH3), 1.20 (t, J = 6.4 Hz, 3H, CH2CH3);
HR-MS (ESI): Calcd. for C8H16NaO3 [M + Na]+: 183.0997,
found 183.0994.
Our method employed inexpensive chlorotrimethylsilane
as silylating agents, which is better than the expensive hexa-
methyldisilazane as silylating regent in the previous method12.
This new route to compound 5 avoided the use of expensive
starting materials and the reaction conditions were very mild.
In the preparation for enynyl aldehyde (6), a selective
oxidation of compound 5 with the aid of collins reagent was
developed. As the product obtained in the collins oxidation
was unstable, the oxidation product was directly dehydrated
with dilute H2SO4 to furnish compound 6. The 1H NMR
spectrum of compound 6 displayed signals for both geometric
isomers (E/Z = 1 : 8.6).
Synthesis of 5-(1-ethoxyethoxy)-3-methylpent-1-yn-3-
ol (10): A solution of compound 9 (0.1 mol) in THF (10 mL)
was added dropwise to ethynylmagnesium bromide12 (0.2
mol) at 0-5 °C over a period of 0.5 h. After addition of com-
pound 9 the reaction mixture was quenched with saturated
NH4Cl and extracted with ethyl acetate (3 × 25 mL). The
combined extracts were washed with brine, dried (Na2SO4)
and evaporated. The crude product was purified by column
chromatography on silica gel (petroleum ether/ethyl acetate =
10:1) to afford a pale yellow liquid. Yield 65 %; FT-IR (film)
(cm-1): 3443, 3295, 2979, 2929, 2884, 2106, 1716, 1379,1130,
1086, 947, 917; 1H NMR (400 MHz, CDCl3): δ (ppm) = 5.16-
5.10 (m, 1H, CHCH3), 4.05-3.80 (m, 2H), 3.71-3.42 (m, 2H),
2.52 (s, 1H, ethynyl), 1.90-1.77 (m, 1H), 1.57-1.53 (m, 1H),
1.50-1.48 (m, 3H, CH3), 1.30-1.27 (m, 3H, CHCH3), 1.22-
1.15 (m, 3H, OCH2CH3); HR-MS (ESI): Calcd. for C10H18NaO3
[M + Na]+: 209.1154, found 209.1150.
Finally, reduction of compound 6 in the presence of
NaBH4 gave a E/Z-mixture of compound 2 (R = H) (E/Z = 1 :
6.3) in 95 % yield.
New derivatives of C6 acetylenic alcohols: The new C6
acetylenic alcohol derivatives compounds (7, 8, 10 and 11)
synthesized in this study contain six-carbon backbone bearing
alkynyl group and hydroxy-protected silyl ethers or acetals. It
is anticipated that the alkynyl group of these derivatives can
react with the carbonyl compounds such as C14-aldehyde8, 4-
hydroxy-2,2,6- trimethylcyclohexanone18 to get the carbon
skeleton of Vitamin A and carotenoids. The silyl ethers or
acetals can be easily deprotected under acidic conditions
followed by the elimination of hydroxy to afford the polyenic
compounds, which can be further converted into Vitamin A
and carotenoids.
Di-silylated compound 7 was obtained in 89 % yield by
treatment of diol compound 5 with chlorotrimethylsilane and
Et3N in dichloromethane. The reaction was easy to handle and
the yield was excellent. Compound 7 possesses two silylated
protecting groups which can be easily deprotected under
weakly acidic conditions. So compound 7 may be appropriate
for synthesizing precursors of carotenoids which were obtained
in weakly acidic conditions.
Synthesis of 4-ethynyl-2,4-dimethyl-1,3-dioxane (11):
Dry hydrogen chloride was bubbled for about 1 h through a
mixture of compound 10 (2.7 mmol) and ethanol (15 mL) at
10-15 °C. After the reaction was completed, the resulting
mixture was washed with saturated sodium bicarbonate, dried
(Na2SO4) and evaporated. The crude product was purified by
column chromatography on silica gel (petroleum ether/ethyl
acetate = 15:1) to afford a green yellow liquid. Yield 57 %;
FT-IR (film) (cm-1): 3293, 2988, 2929, 2867, 2106, 1728, 1402,
Mixed acetals compound 8 was prepared in 95 % yield
by addition of diol compound 5 with ethyl vinyl ether under
1
1260, 1192, 1136, 1095, 944, 858; H NMR (400 MHz,

638 Pu et al.
Asian J. Chem.
the catalysis of pyridine and p-TsOH. Compared with
compound 7, the compound 8 was more stable and could be
suitable for the synthesis of carotenoids' precursors which are
acquired under harsh conditions.
characterization was accomplished by Sichuan University
Analytical & Testing Center.
REFERENCES
Acetal compound 10 was synthesized in 65 % yield by
the ethynylation reaction of 4-hydroxy-2-butanone (3) with
ethynylmagnesium bromide.
1. E.R.H. Jones, J. Chem. Soc., 754 (1950).
2. B. Werne and N. Thomas, WO2012175398 (2012).
3. V.R. Preedy, Vitamin A and Carotenoids: Chemistry, Analysis, Func-
tion and Effects, RSC Publishing: Cambridge (2012).
Cyclic acetal compound 11 was achieved in 57 % yield
via a convenient cyclization of compound 10 in the presence
of HCl (g). Acetal compound 11 possessing a quite stable six-
membered ring can be used to prepare carotenoids' precursors.
In addition, analogues of acetal compound 11 had been widely
used in the synthesis of important natural products19-21, espe-
cially oxygen-containing heterocyclic compounds. So this
method will find its potential applications and advantages in
building similar structures of acetal compound 11.
The structural elucidation of these new derivatives was
assigned on the basis of their IR, 1H NMR and mass spectra
analysis. The IR spectra of compounds 7, 8, 10, 11 showed
the absorption bands at 2140-2100 cm-1 related to ethynyl
groups. In the 1H NMR spectra, a singlet at δ = 2.47-2.55 ppm
was assigned to the absorption peak of ethynyl groups. The
absorption peaks of all other protons were also appeared in
the expected region.
4. M. Eggersdorfer, D. Laudert, U. Létinois, T. McClymont, J. Medlock,
T. Netscher and W. Bonrath, Angew. Chem. Int. Ed., 51, 12960 (2012).
5. M. Rosenberger, P. McDougal and J. Bahr, J. Org. Chem., 47, 2130
(1982).
6. E. Hansgeorg and D. Walter, US Patent 5455362 (1995).
7. F. Kienzle and H. Mayer, Helv. Chim. Acta, 61, 2609 (1978).
8. I. Heilbron, J. Chem. Soc., 386 (1948).
9. J. Cymerman, I.M. Heilbron, A.W. Johnson, E.R.H. Jones, J. Chem.
Soc., 141 (1944).
10. K.R. Martin, C.W. Kamienski, M.H. Dellinger and R.O. Bach, J. Org.
Chem., 33, 778 (1968).
11. J. Cymerman, I.M. Heilbron and E.R.H. Jones, J. Chem. Soc., 90 (1945).
12. S.H. Lee and S.T. Kadam, Appl. Organomet. Chem., 25, 608 (2011).
13. A. Fürstner, L.C. Bouchez, L. Morency, J.A. Funel, V. Liepins, F.H.
Porée, R. Gilmour, D. Laurich, F. Beaufils and M. Tamiya, Chem. Eur.
J., 15, 3983 (2009).
14. D. Buser, H. Pauling,A. Thum andW. Bonrath, Molecules, 7, 341 (2002).
15. A. K. GhoshJ. F. Li. A.K. Ghosh and J. Li, Org. Lett., 11, 4164 (2009).
16. M. Feliks and E. Rimma, SU1198080 (1985).
17. E.E. Boehm, V. Thaller and M.C. Whiting, J. Chem. Soc., 2535 (1963).
18. A.N. Chang, Doctoral Dissertation, Total Synthesis of (3R, 3'R, 6'R)-
Lutein, (3R, 3'R)-Zeaxanthin and Their Stereoisomers, University of
Maryland, USA (2008).
In conclusion, it is reasonable to assume that these C6
acetylenic alcohol derivatives will be potentially utilized in
the synthesis of Vitamin A and carotenoids. Further efforts to
synthesize Vitamin A and carotenoids using these new C6
acetylenic alcohol derivatives are now in progress and will be
reported in the near future.
19. O. Robles and F.E. McDonald, Org. Lett., 10, 1811 (2008).
20. E.V. Dehmlow and M. Lissel, Tetrahedron Lett., 17, 1783 (1976).
21. A. Mames, S. Stecko, P. Mikolajczyk, M. Soluch, B. Furman and M.
Chmielewski, J. Org. Chem., 75, 7580 (2010).
ACKNOWLEDGEMENTS
The work was financially supported by the National
Science Foundation of China (No. 21072135). The 1H NMR