Air-stable Organoantimony (III) Perfluoroalkyl(aryl)sulfonate complexes as highly efficient, selective, and recyclable catalysts for C–C and C–N bond-forming reactions

Article abstract of DOI:10.1016/j.mcat.2021.111727

A series of air-stable organoantimony (III) perfluoroalkyl(aryl)sulfonate complexes with an azastibocine framework {t-BuN(CH₂C₆H₄)₂SbOSO₂C₄F₉ (2a); [t-BuN(CH₂C₆

Full text of DOI:10.1016/j.mcat.2021.111727

Molecular Catalysis 511 (2021) 111727
Contents lists available at ScienceDirect
Molecular Catalysis
journal homepage: www.journals.elsevier.com/molecular-catalysis
Air-stable Organoantimony (III) Perfluoroalkyl(aryl)sulfonate complexes as
highly efficient, selective, and recyclable catalysts for C–C and C–N
bond-forming reactions
,
b
,
c
,
,
,*
Ningbo Lia
*, Qi Fana, Li Xua, Rong Maa, Shitang Xud, Jie Qiaob c, Xinhua Xud
,
,c,
Rui Guoa *, Kemin Yune
a Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan 030001, P. R. China
b Department of Chemistry, School of Basic Medical Sciences, Shanxi Medical University, Jinzhong 030619, P.R.China
c Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China
d College of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082, P. R. China
e School of Forensic Medicine, Shanxi Medical University, Jinzhong 030619, P.R. China
A R T I C L E I N F O
A B S T R A C T
Keywords:
A series of air-stable organoantimony (III) perfluoroalkyl(aryl)sulfonate complexes with an azastibocine
framework {t-BuN(CH2C6H4)2SbOSO2C4F9 (2a); [t-BuN(CH2C6H4)2Sb(OH2)]+[OSO2X]ꢀ , [X = C6F5, (2b); C8F17
,
Organoantimony
Perfluoroalkyl(aryl)sulfonate
Highly selective
(2c)]} was synthesized and systematically characterized. These complexes exhibited good thermal stability and
relatively strong Lewis acidity. Moreover, they showed high catalytic efficiency, selectivity and recyclability for
Strecker reaction, Mannich-type reaction, cross-condensation of aldehydes with ketones, and amination of ep-
oxides. Such complexes were applied to extend the synthesis of seven novel carbazole derivatives, which showed
good inhibitory activity against CHT116 cells and HepG2 cells.
C-C(N) bond-forming
Carbazole derivative
1. Introduction
acidity and electron-deficient complex of R3SbX2 is obtained [36-38]
(Scheme 1b). For example, triphenylantimony (V) dichloride was first
Organoantimony complexes have attracted considerable attention in
organic synthesis and as reagents in catalysis [1-6], pharmaceuticals
[7-9], and materials science [10-13] because of their particular bound-
ary (metal and non-metal, [Kr]4d105s25p3) features [14], large reserves
in nature [15], and relatively low cost antimony metal compared with
transition metals (Pd, Pt, Ru, and Rh). Many groups have published their
contributions in the synthesis and structure of organoantimony com-
plexes [16,17] and their in vitro anti-tumor activity [18-22] and organic
reactivity [23-27]. However, their application as a Lewis acid catalyst in
organic synthesis has rarely been referred [28-32], which can be
attributed to the weak acidity and activity given their stable and filled
4d- and 5s-obitals and half-filled 5p-obitals. Therefore, their Lewis
acidity (empty 5p and/or 5 s orbitals) or basicity (fulfilled 5s-obitals)
depends on the environment of the chelating or bonding ligand [33,
34]. For example, R3Sb (Scheme 1a) has low catalytic efficiency, but it
can be used as ligand to coordinate with a Pd catalyst, which is an ad-
ditive, because of the lone pair of 5s2 electrons [35]. After the 5s2
electrons withdraw by the electron-deficient groups, the high Lewis
reported by Nomura et al. as a highly efficient catalyst in the chemical
fixation of CO2 to useful chemicals [39]. Our group disclosed two
binuclear triphenylantimony (V) complexes, which showed high cata-
lytic efficiency in C–C bond formation reaction [40]. In addition, a
hypervalent organoantimony(III) complex, which was unknown until
2009, was used as a Lewis acid catalyst (Scheme 1c) [41]. In recent
years, Yin and Tan reported several hypervalent organoantimony(III)
complexes with an azastibocine framework, which could efficiently
catalyze various organic reactions [42-45]. Meanwhile, the long pair of
electrons in the nitrogen atom may not only coordinate with antimony
to stabilize the complex but also serve as a basic site, thereby showing a
bifunctional catalytic efficiency.
However, the R groups in the abovementioned complexes are rigid
phenyl or cyclohexyl groups, and organoantimony complexes with a
flexible group, such as tertiary butyl in the azastibocine framework,
have been rarely reported as a Lewis catalyst. This finding may indicate
that with the increase in the basicity of nitrogen (N) atom, the acidity of
the antimony (Sb) center becomes weak. Therefore, perfectly balancing
* Corresponding authors.
E-mail addresses: ningboli@sxmu.edu.cn (N. Li), xhx1581@hnu.edu.cn (X. Xu), ruiguo@sxmu.edu.cn (R. Guo).
https://doi.org/10.1016/j.mcat.2021.111727
Received 21 March 2021; Received in revised form 17 May 2021; Accepted 21 June 2021
Available online 3 July 2021
2468-8231/© 2021 Elsevier B.V. All rights reserved.

N. Li et al.
Molecular Catalysis 511 (2021) 111727
2. Experimental section
All chemicals were purchased from Energy Chemical. Co., Ltd. and
used as received unless otherwise indicated. Organoantimony chloride
(1) was prepared as described previously [2]. The catalyst was prepared
under the protection of nitrogen with fresh distilled solvent. The nuclear
magnetic resonance (NMR) spectra were recorded on a Varian 400 M Hz
spectrometer (USA) in CDCl3. Thermogravimetry-differential scanning
calorimetry (TG-DSC) analysis was performed on an STA 449C instru-
ment (NETZSCH, Shanghai, China). IR spectra were recorded on a
Thermo Scientific Nicolet iS50 spectrophotometer (USA). Elemental
analyses were performed using a PerkinElmer 2400 II instrument (USA).
X-ray single crystal diffraction analysis was performed with a D8 Ven-
ture diffractometer (Bruker, Germany). Acidity was measured using the
Hammett indicator method as described previously [47]. Two human
cancer cell lines, namely, HCT 116 (colorectal carcinoma) and HepG2
(hepatoma) were kindly provided by Stem Cell Bank, Chinese Academy
of Sciences (Shanghai, China).
Scheme 1. Three types of organoantimony complexes.
the Lewis basicity of nitrogen atom and the Lewis acidity of central
antimony atom remains a problem that needs to be solved.
This study adopted the azastibocine framework with tertiary butyl
and modulated the electron-withdrawing nature of the perfluoroalkyl
(aryl)sulfonate groups [46-51] connected to nitrogen and antimony
atoms to modify the Sb→N coordination distance, increasing the Lewis
acidity of antimony (Sb) center and maintaining the good performance
of the nitrogen (N) atom as Lewis base. Consequently, we have suc-
cessfully synthesized and characterized a series of air-stable and
water-tolerant organoantimony (III) perfluoroalkyl(aryl)sulfonate
complexes {t-Bu N(CH2C6H4)2SbOSO2C4F9 (2a); [t-Bu N(CH2C6H4)2Sb
(OH2)]+[OSO2X]ꢀ , [X = C6F5, (2b); C8F17, (2c)]}. Furthermore, we have
systematically assessed their catalytic activities and selectivities using
Lewis acid-catalyzed C–C and C–N bond-forming reactions, such as the
Strecker reaction, Mannich-type reaction, cross-condensation of ketones
and aldehydes, and amination of epoxides (Fig. 1).
2.1. Preparation of organoantimony chloride 1
A solution of t-BuN(CH2C6H4Br)2 (4.28 g, 10 mmol) in 100 mL of
anhydrous Et2O was added to n-BuLi (8.2 mL, 2.5 M) in hexane at ꢀ 30
◦C for 30 min. The temperature of the mixture was allowed to increase
slowly to room temperature for 30 min. After SbCl3 (2.33 g, 10.2 mmol)
was added in 50 mL of anhydrous Et2O solution to the mixture at ꢀ 78 ◦C
Fig. 1. Organoantimony complex-catalyzed C–C and C–N bond-forming reactions.
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N. Li et al.
Molecular Catalysis 511 (2021) 111727
within 30 min, the as-obtained mixture was kept at ꢀ 78 ◦C for 10 h. The
reaction temperature was slowly increased to room temperature over-
night. The resulting mixture was diluted with CHCl3 (80 mL), washed
with 1 M NH4Cl in H2O solution, and subjected to filtration. The organic
layer was washed with deionized water (3 × 30 mL), dried with Na2SO4,
and subjected to filtration and evaporation to obtain the crude product.
After recrystallization in CH2Cl2/hexane solution, the colorless crystals
of compound 1 were obtained (3.34 g, 82%). Mp:212–214 ◦C; 1H NMR
(400 MHz, CDCl3): δ = 8.06 (d, J = 8.4 Hz, 2H), 7.20–7.10 (m, 6H), 4.46
(d, J = 15.6 Hz, 2H), 3.91 (d, J = 16.0 Hz, 2H), 1.26 (s, 9H); 13C NMR
(100 MHz, CDCl3): δ = 151.4, 145.1, 139.6, 139.5, 134.1, 133.1, 130.2,
65.8, 62.2, 31.5; Anal. Calc. for C18H21ClNSb: C, 52.91; H, 5.18; N, 3.43.
Found: C, 52.88; H, 5.25; N, 3.40.
in air, the filtrate mixed with dry n-hexane (5 mL) was refrigerated for
24 h to obtain the colorless crystals (0.693 g, 78%). Mp: 189–191 ◦C; 1H
NMR (400 MHz, acetone-d6): δ = 8.00 (s, 2H), 7.39–7.35 (m, 6H), 4.83
(d, J = 16.0 Hz, 2H), 4.27 (d, J = 16.0 Hz, 2H), 3.02 (s, 2H), 1.49 (s, 9H);
19F NMR (376 MHz, CDCl3): ꢀ 81.62 to ꢀ 81.68 (m, 3F; CF3-), ꢀ 115.22 to
ꢀ 115.33 (m, 2F; -CF2-), ꢀ 121.05 to ꢀ 121.16 (m, 2F; -CF2-), ꢀ 122.10 to
ꢀ 122.20 (m, 4F; -CF2-), ꢀ 123.20 to ꢀ 123.30 (m, 2F; -CF2-), ꢀ 126.69 to
ꢀ 126.76 (m, 2F; -CF2-); IR(KBr):
ν = 3328, 3198, 3076, 1650, 1483,
1444, 1411, 1365, 1252, 1137, 1059, 1024, 989, 939, 761, 739, 690,
626, 548 cmꢀ 1; Anal. Calc’d for C26H23F17NO4SSb: C, 35.08; H, 2.60; N,
1.57; Found: C, 35.13; H, 2.64; N, 1.66.
2.5. Typical procedure for the Strecker reaction catalyzed by 2a
2.2. Preparation of complex 2a
Complex 2a (0.05 mmol), aldehydes/ketones (1.0 mmol), anilines
(1.0 mmol), and trimethylsilylcyanide (1.2 mmol) were mixed in a 25
mL round-bottom flask. Then, the mixture was stirred at room temper-
ature under TLC analysis until the reaction was complete. The mixture
was dissolved in Et2O, and the catalyst was collected by filtration for the
next cycle of reaction. After the filtrate solvent was evaporated, a pale
yellow solid mixture was obtained. The crude products were purified by
silica gel column chromatography (petroleum ether/ethyl acetate = 8:1
to 5:1) to obtain the desired products 6.
t-BuN(CH2C6H4)2SbCl (0.407 g, 1 mmol) was dissolved in THF(15
mL). A solution of AgOSO2C4F9 (0.84 g, 2 mmol) in 10 mL of THF was
added using a syringe under the protection of nitrogen, and the mixture
was stirred for 2 h at room temperature in the absence of light. After
filtering in air, the filtrate mixed with dry n-hexane (5 mL) was refrig-
erated for 24 h to obtain the colorless crystals (0.563 g, 84%). Mp:
185–187 ◦C, 1H NMR (400 MHz, acetone-d6): δ = 8.18 (d, J = 8.0 Hz,
2H), 7.76–7.63 (m, 6H), 5.00 (d, J = 16.0 Hz, 2H), 4.23 (d, J = 16.0 Hz,
2H), 1.32 (s, 9H); 19F NMR (376 MHz, [d6] acetone): δ: ꢀ 81.73 to
ꢀ 81.80 (m, 3F; CF3-), ꢀ 114.85 (s, 2F; -CF2-), ꢀ 121.89 to ꢀ 121.92 (m,
2.6. Typical procedure for the Mannich-Type reaction catalyzed by 2b
2F; -CF2-), ꢀ 126.54 to ꢀ 126.63 (m, 2F; -CF2-); IR(KBr):
ν
= 3474, 3056,
Complex 2b (0.05 mmol), aldehydes (1.0 mmol), anilines (1.0
mmol), and enol silyl ethers (1.2 mmol) were added to a 25 mL round-
bottom flask. Then, the mixture was stirred at room temperature under
TLC analysis until the reaction was complete. The mixture was dissolved
in Et2O, and the catalyst was collected by filtration for the next cycle of
reaction. After the filtrate solvent was evaporated, a white solid mixture
was obtained. The crude products were purified by silica gel column
chromatography (petroleum ether/ethyl acetate = 10:1 to 5:1) to obtain
the desired products 8.
2978, 2926, 2855, 1465, 1385, 1350, 1307, 1220, 1141, 1047, 1004,
968, 905, 834, 755, 700, 653, 589 cmꢀ 1
; Anal. Calc’d for
C
22H21F9NO3SSb: C, 39.31; H, 3.15; N, 2.08; Found: C, 39.36; H, 3.20; N,
2.10.
2.3. Preparation of complex 2b
t-BuN(CH2C6H4)2SbCl (0.407 g, 1 mmol) was dissolved in CH3CN
(15 mL). A solution of AgOSO2C6F5 (0.71 g, 1.0 mmol) in 10 mL of
CH3CN was added under nitrogen atmosphere, and the mixture was
stirred for 2 h at room temperature in the absence of light. After filtering
in air, the filtrate was evaporated in a vacuum, and the resulting residue
was diluted with THF (10 mL). Finally, the filtrate mixed with dry n-
hexane (1 mL) was refrigerated for 24 h to obtain the colorless crystals
(0.516 g, 81%). Crystals suitable for single-crystal X-ray diffraction
analysis were obtained by crystallization of 2b from the THF/n-hexane
solvent. Mp: 210–212 ◦C; 1H NMR (400 MHz, acetone-d6): δ = 8.01–7.98
(m, 2H), 7.38–7.32 (m, 6H), 4.84 (d, J = 15.6 Hz, 2H), 4.26 (d, J = 15.6
Hz, 2H), 3.08 (s, 2H), 1.48 (s, 9H); 19F NMR (376 MHz, CDCl3): ꢀ 138.85
to ꢀ 126.97 (m, 2F), ꢀ 153.82 (s, 1F), ꢀ 162.17 to ꢀ 163.34 (m, 2F); IR
2.7. Typical procedure for the cross-condensation reaction catalyzed by
2c
Complex 2c (0.05 mmol), ArCHO (1.0 mmol), n-PrNH2 (1.0 mmol),
ketones (3.0 mmol), and H2O (2.0 mL) were added to a 25 mL round-
bottom flask. The mixture was stirred for 24 h and monitored by TLC
analysis. After the reaction was completed, the solvent was removed
under vacuum. Then, the residue was dissolved in Et2O, and the catalyst
was separated from the mixture by filtration for the next cycle of reac-
tion. The filtrate was subjected to evaporation in vacuum. The crude
products were purified by silica gel column chromatography (petroleum
ether/ethyl acetate = 8:1 to 4:1) to obtain the desired products 10.
(KBr):
ν = 3259, 3043, 2989, 1645, 1517, 1491, 1411, 1309, 1265,
1221, 1105, 1046, 980, 907, 827, 754, 622, 520 cmꢀ 1; Anal. Calc’d for
C
24H23F5NO4SSb: C, 45.16; H, 3.63; N, 2.19; Found: C, 45.22; H, 3.65; N,
2.8. Typical procedure for epoxide ring-opening reaction with amines
2.25.
Crystal data for 2b: C24H23F5NO4SSb; Mr = 638.24, Triclinic, space
catalyzed by 2c
group P-1, a = 10.7995(5) Å, b = 10.9852 (5) Å, c = 10.39960 (4) Å; V =
1190.32(9) Å 3; T = 293(2) K; Z = 2; Reflections collected/unique,
4186/3781, Rint = 0.0533, R1 = 0.0311, wR2 = 0.0506; GOF = 1.043;
CCDC-1,565,687 contains the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The Cam-
bridge Crystallographic Data centre via www.ccdc.cam.ac.uk/data_re
quest/cif.
Complex 2c (0.05 mmol), epoxides (1.0 mmol), and amines (1.0
mmol) were added to a 25 mL round-bottom flask. Then, the mixture
was stirred at room temperature for 2–6 h. After the reaction was
completed (TLC analysis), the resulting mixture was subjected to evap-
oration, and the residue was dissolved in Et2O. The catalyst was
precipitated and separated by filtration for the next cycle of reaction.
Then, the filtrate was evaporated under reduced pressure. The crude
products were purified by silica gel column chromatography (petroleum
ether/ethyl acetate = 10:1 to 5:1) to obtain the desired products 12.
2.4. Preparation of complex 2c
t-BuN(CH2C6H4)2SbCl (0.407 g, 1 mmol) was dissolved in THF(15
mL). A solution of AgOSO2C8F17 (1.21 g, 2 mmol) in 10 mL of THF was
added using a syringe under the protection of nitrogen, the mixture was
stirred for 2 h at room temperature in the absence of light. After filtering
2.9. Typical procedure for catalyst recovery and reuse (Strecker reaction
as an example)
Complex 2a (168 mg, 0.25 mmol), PhCHO (530 mg, 5 mmol), PhNH2
3

N. Li et al.
Molecular Catalysis 511 (2021) 111727
organoantimony chloride (1) with AgOSO2X (X = C4F9, 2a; C6F5, 2b;
C8F17, 2c) in THF or CH3CN for 2 h.
Complexes 2a–2c remained stable as a white powder or colorless
crystals in open air over 3 months and did not exhibit any detectable
change upon 1H NMR spectroscopic analysis (Fig. S1, ESI). The freshly
prepared samples contained 0 or 1 water molecule for 2a, 2b, and 2c, as
indicated by the results of 1H NMR and elemental analysis. Therefore,
complex 2a may have a covalent structure, and complexes 2b and 2c are
ionic complexes in solid state and are similar to the previously reported
binuclear triphenylantimony complexes [40]. The scanning electron
microscopy (SEM) image results of complexes 2a–2c show a platelet-like
crystal shape (Fig. S3, ESI). The crystal structure of complex 2b was
achieved by diffusion of hexane into a saturated solution of 2b in THF.
As shown in Fig. 2, complex 2b is an ionic compound, and the cationic
antimony-containing part shows a pseudo-trigonal bipyramidal struc-
ture with a butterfly-shaped ligand. This structure is where the nitrogen
and oxygen atoms are located at the apical position, and the two adja-
cent carbon atoms exist in the equatorial positions along with a lone
electron pair of Sb. The length of the N→Sb coordinate bond is 2.379(2)
Å, which is between the length of the N-Sb covalent bonds (2.11 Å) [52]
and the sum of the van der Waals radii (3.74 Å) [53], indicating that the
intramolecular coordination between antimony and nitrogen atoms was
weak. The anionic C6F5SOꢀ3 ion was packed around the antimony cation
to improve water tolerance and enhance the Lewis acidity.
Scheme 2. Synthesis of organoantimony complexes 2a–2c.
(530 mg, 5 mmol), and TMSCN (119 mg, 6 mmol) was mixed in a 50 mL
round-bottom flask. The mixture was stirred at room temperature under
TLC analysis until the reaction was complete (the intermediate N-ben-
zylideneaniline was consumed completely). Then the mixture was
diluted with Et2O, and the catalyst was collected by filtration. The
recovered catalyst was washed three times with Et2O (10 mL × 3) for the
next cycle of reaction. After the filtrate solvent was evaporated, a pale
yellow solid mixture was obtained. The crude products were purified by
silica gel column chromatography (petroleum ether/ethyl acetate = 5:1)
to obtain the desired products 6a. Other reaction procedures for catalyst
recovery are similar.
We evaluated the thermal stability of the complexes by TG-DTA
analysis under N2 atmosphere, and the result is shown in Fig. 3. Com-
plexes 2a, 2b, and 2c are stable up to approximately 285 ◦C, 290 ◦C, and
340 ◦C, respectively, and the endothermic peak that appears at
approximately 200 ◦C indicates that fusion occurred because no weight
loss has been observed. Complex 2c has better thermal stability than the
other complexes, which may be due to the long-chain perfluorooctyl
group. As shown in the TG-analysis results, complex 2a did not contain
coordinated water molecule, but complex 2b or 2c contained one water
molecule, which was consistent with the results of 1H NMR and
3. Results and discussion
3.1. Preparation, characterization, and physiochemical property of
complexes 2a–2c
As shown in Scheme 2, organoantimony perfluoroalkyl(aryl)sulfo-
nate complexes 2a–2c were synthesized by treatment with
Fig. 2. ORTEP view of the crystal structure of 2b and selected bond lengths (Å) and angles (deg): Sb-C1, 2.147(3); Sb-C14, 2.26(3); Sb-N, 2.379(2); Sb-O4, 2.297(18);
S-O2, 1.432(2); S-O1, 1.446(2); S-O3, 1.452(2); C14-Sb-C1 99.65(10); C14-Sb-O4 89.72(9); C1-Sb-O4 87.34(9); and O4-Sb-N1 158.09(7).
4

N. Li et al.
Molecular Catalysis 511 (2021) 111727
Fig. 3. TG-DTA curves of complexes 2a–2c.
Table 1
Strecker reaction catalyzed by complex 2aa.
aCatalyst 2a (0.05 mmol); aldehydes/ketones (3; 1.0 mmol); 1.0 mmol; amines (4; 1.0 mmol); trimethylsilyl cyanide (5; 1.2 mmol); solvent-free; RT; 6a-6m, 1 h; 6n
and 6o, 6 h; isolated yield.
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N. Li et al.
Molecular Catalysis 511 (2021) 111727
elemental analysis.
isolated yield, thereby showing high compatibility for this reaction (6 g,
6 h, and 6 m respectively). Meanwhile, n-butylaldehyde can react with
aniline and trimethylsiloxynitrile, resulting in the 82% yield of 6i. The
presence of substituents in the phenylamine source and heterocyclic 8-
aminoquinoline had a negligible effect on the reaction efficiency (6j,
6k, and 6l). Acetophenone and cyclohexanone can also be transformed
to the corresponding product with 73% and 68% yield (6n and 6o).
Next, we investigated the solubility and acidity of complexes 2a–2c.
These organoantimony complexes possess good solubility in common
polar solvents, such as THF, acetone, acetonitrile, and MeOH, but are
insoluble in CH2Cl2, Et2O, n-hexane, and toluene (Table S1, ESI). The
Lewis acidity of complexes 2a–2c was estimated via the Hammett in-
dicator method with strength of 3.3 < H0 < 4.8 (Fig. S2, ESI), indicating
relatively strong acidity [54]. On the basis of the features of the
abovementioned complexes, we assessed their catalytic activities and
diastereoselectivities in four organic reactions: (i) the Strecker reaction,
(ii) Mannich-type reaction, (iii) cross-condensation of aldehydes with
ketones, and (iv) amination of epoxides.
3.3. Mannich-type reaction catalyzed by complex 2b
The Mannich-type reaction is often used to prepare β-amino carbonyl
compounds, which are important components of biologically active
molecules [55-58]. However, solving the side reaction problem pro-
duced by aldehydes and enol silyl ethers remains a challenge [59]. Thus,
the catalytic performance of complex 2b was evaluated using the
Mannich-type reaction of aldehydes with anilines and enol silyl ethers
(Table S3, optimal conditions in the ESI). As shown in Table 2, a variety
of β-amino carbonyl compounds can be conveniently and efficiently
obtained via a complex 2b-catalyzed Mannich-type reaction. In general,
aromatic aldehydes with various functional groups (such as
electron-rich and electron-deficient groups) at the para and meta posi-
tions, react smoothly to obtain the corresponding products with
good-to-excellent yields (8a–8 g). Naphthaldehyde and 5-nitro-2-fural-
dehyde can be used in this reaction condition, providing compounds
8 h and 8i with 90% and 91% yields, respectively. Meanwhile, the re-
action proceeds well with substituted anilines, providing the desired
3.2. Strecker reaction catalyzed by complex 2a
First, we assessed complex 2a for the one-pot three-component
Strecker reaction to demonstrate its catalytic efficiency (Table S2,
optimal conditions in the ESI). As shown in Table 1, the Strecker reac-
tion of aldehydes/ketones with anilines and trimethylsilyl cyanide
proceeded well. The byproduct nitrile alcohol of the competitive reac-
tion was not detected, indicating the good selectivity of 2a for Strecker
reaction. Aromatic aldehydes with electron-withdrawing (F, Cl, Br) and
electron-donating (CH3, OCH3) groups can react smoothly with aniline
and trimethylsilyl cyanide to obtain α-aminonitriles (6a–6f, 88%–96%),
and aldehydes with electron-withdrawing groups showed higher reac-
tivity. Furfural, cinnamaldehyde, and 4-quinolinecarboxaldehyde pro-
vide the corresponding products with respective 91%, 87%, and 83%
products
with
high
yields
(8j
and
8k).
Notably,
Table 2
Mannich-type reaction by complex 2b a.
aCatalyst 2b (0.05 mmol); aldehydes (3; 1.0 mmol); amines (4; 1.0 mmol); enol silyl ethers (7; 1.2 mmol); solvent-free; RT; 8a-8k, 0.5 h; 8l, 3 h; isolated yield.
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N. Li et al.
Molecular Catalysis 511 (2021) 111727
((1-Methoxy-2-methylprop-1-en-1-yl)oxy)trimethylsilane is also suit-
bifunctional Lewis acidic/basic feature of complex 2c in synthesizing
able for the transformation, providing compound 8l with 82% yield.
E-selective α, β-unsaturated ketones.
3.4. Cross-condensation reaction catalyzed by complex 2c
3.5. The epoxide ring-opening reaction catalyzed by complex 2c
We adopted complex 2c as a catalyst for the cross-condensation re-
action of aromatic aldehydes and ketones to explore its stereoselectivity
(Table S4, optimal conditions in the ESI). As shown in Table 3, using
organoantimony complex 2c as a catalyst, we obtained moderate-to-
Finally, we applied complex 2c as a catalyst for epoxide ring-opening
reaction with aromatic amines to explore the stereoselectivity of cis and
trans isomers (Table S5, optimal conditions in the ESI). As shown in
Table 4, non-activated aromatic amines with either an electron-deficient
(F, Cl) or an electron-rich (CH3, OCH3) group show good reactivity with
cyclohexene oxide in obtaining the only trans-β-aminoalcohol products
(12a–12 g), indicating the high stereoselectivity of catalyst 2c. In the
cases of o-toluidine and 2, 5-dimethoxyaniline with a large steric effect
(12e and 12 g), satisfactory yields (84% and 90%) can be achieved.
When 2-phenyloxirane, which can react with different aromatic amines,
good yields of (E)-α, β-unsaturated ketones (70%–90%) with trace of
Z-isomer (not isolable). Previous reports indicated that syn-elimination
of the Mannich intermediates is the primary cause of E-selective product
formation [60]. Therefore, a particular butterfly-shaped structure and
anion with large electron-withdrawing ability can significantly improve
the stereoselectivity and catalytic efficiency for cross-condensation re-
action. Aromatic aldehydes and ketones with electron-withdrawing
groups (F, Cl and Br) showed better stereoselectivity than those with
electron-donating groups (CH3 and t-Bu) (10b–10j). The reaction was
compatible with the CN group in terms of achieving high yields of the
desired E configuration products (10k and 10l). Next, other ketones,
such as 2-acetonaphthone and acetone are suitable substrates for this
transformation and can generate the corresponding products (10 m and
10n). Thus, the high stereoselectivity can be attributed to the
was adopted as the epoxide, the
α-amino product with high regio-
selectivity was obtained ( /β>97/3, 12h–12j, 90%–94% yield). More-
α
over, epoxypropane with low activity can be used as an epoxy source to
provide the only β-aminoalcohol product with 80% yield. Remarkably,
enantiomerically pure chiral (R)ꢀ 2-phenyloxirane was converted into
their corresponding ring-opening products without racemization (12h′),
indicating that catalyst 2c had no effect on the chiral center of the
product (chromatograms in the ESI).
Table 3
Cross-condensation reaction catalyzed by 2ca.
aCatalyst 2c (0.05 mmol); aldehydes (3; 1.0 mmol); n-PrNH2 (1.0 mmol); ketones (9; 1.2 mmol); solvent: H2O (2 mL); RT; 24 h; isolated yield; determined by 1H NMR
for E/Z ratio.
7

N. Li et al.
Molecular Catalysis 511 (2021) 111727
Table 4
Amination reaction of epoxides catalyzed by 2c a.
aCatalyst 2c (0.05 mmol); epoxides (11; 1.0 mmol); aromatic amines (4; 1.0 mmol); solvent-free; RT; 12a-12g, 4 h; 12h-12j 2 h; 12k, 6 h; isolated yield; bα/β = 97/3,
determined by GC-MS and 1H NMR analysis of the product; cstereoisomer was determined by chiral HPLC (AD-H column); d100%
product.
α
-amino pruduct; e100% β-amino
3.6. Comparison of the catalyst with other catalytic systems
catalyst were the same, and their morphological structures were similar
after the recycling run (Fig. S3–S6, ESI), indicating that the catalyst is
suitable for reuse.
We compared the catalytic activities and stereoselectivities of orga-
noantimony perfluoroalkyl(aryl)sulfonate complexes with other anti-
mony compounds, such as SbCl3, Ph3SbCl2, t-BuN(CH2C6H4)2SbCl, and
t-BuN(CH2C6H4)2SbOTf, to demonstrate their advantage. Table 5 shows
that catalysts, such as antimony trichloride, triphenylantimony
dichloride, and organoantimony chloride with an azastibocine frame-
work had low yields (entries 1–3), probably because of their sensitivity
to moisture or their weak Lewis acidity. Although catalysts such as t-BuN
(CH2C6H4)2SbOTf exhibited good catalytic efficiency, their diaster-
eoselectivity was poor (entry 4). By contrast, complexes 2a–2c showed
high yields and stereoselectivities (entries 5–7), particularly, complex
2c, which was sui` for catalyzing the cross-condensation reaction,
thereby indicating its potential industrial application for organo-
antimony bifunctional catalytic systems. For comparison, previous re-
ports on other homogeneous and heterogeneous catalysts are
summarized in Table 5 (entries 8–18) [56,61-70]. The results showed
suggest the advantages of complexes 2a–2c as follows i) mild conditions
ii) solvent-free or H2O as a solvent condition, iii) a wide substrate scope,
iv) high efficiency, and v) good reusability.
3.8. Synthesis of carbazole derivatives and antitumor activity study
Carbazole derivatives are a class of important heterocyclic com-
pounds possessing high biological activity, such as anticancer, anti-
inflammatory, and anti-HIV effects [71]. Given their good catalytic
performance, we synthesized a series of novel carbazole derivatives (6p,
6q, 8 m, 8n, 10o, 12l, and 12 m) using the abovementioned reactions
catalyzed by complexes 2a–2c (Fig. 5a). Furthermore, we screened the
antiproliferative activities of such compounds in two human cancer cell
lines (colorectal carcinoma HCT116 cells and hepatoma HepG2 cells)
using the CCK-8 assay (Fig. 5b). The compounds showed good inhibitory
activity for the two human cancer cell lines at the low
values of approximately 30 M. Notably, compound 6p, with IC50 of
21.25 M in HCT116, had a better inhibitory activity than the other
μM level, with IC50
μ
μ
compounds. However, the presence of a C = C double bond in compound
10o resulted in a remarkable decrease in activity in the two cell lines.
Therefore, these carbazole derivatives showed slightly enhanced activ-
ity against CHT116 cells compared with that against HepG2 cells.
Further bioactivity investigation is still underway in our laboratory.
3.7. Reusability of complexes 2a–2c
We evaluated the reusability of these catalysts, which were subjected
to the following reactions (Eq 1: 3a + 4a + 5 →6a; Eq 2: 3a + 4a + 7a →
8a; Eq 3: 3a + 9a → 10a; Eq 4: 4a + 11a → 12a). Catalysts 2a–2c had
good recycling ability at least five times without a significant decrease in
catalytic efficiency (Fig. 4). The 1H NMR and SEM results indicated that
the skeleton structures of recycled sample and the freshly prepared
4. Conclusions
In conclusion, we adopted an azastibocine framework with tertiary
butyl and synergistically modulated the properties of tert‑butyl nitrogen
and the electron-withdrawing nature of the perfluoroalkyl(aryl)sulfo-
nate groups adjacent to the antimony atom to synthesize and
8

N. Li et al.
Molecular Catalysis 511 (2021) 111727
Table 5
Catalyst comparison of antimony compounds and other catalytic systems.
aCat. (0.05 mmol); PhCHO (1.0 mmol); PhNH2 (1.0 mmol); TMSCN (1.2 mmol); solvent-free; RT.; 1 h; bCat. (0.05 mmol); PhCHO (1.0 mmol); PhNH2 (1.0 mmol);
trimethyl((1-phenylvinyl)oxy)silane (1.2 mmol); solvent-free; RT.; 0.5 h; cCat. (0.05 mmol); PhCHO (1.0 mmol); n-PrNH2 (1.0 mmol); PhCOCH3 (1.2 mmol); solvent:
H2O (2 mL); RT.; 24 h; dCat. (0.05 mmol); cyclohexene oxide (1.0 mmol); PhNH2 (1.0 mmol); solvent-free; RT.; 4 h; eisolated yield.
9

N. Li et al.
Molecular Catalysis 511 (2021) 111727
Fig. 4. Recycling tests for complexes 2a–2c.
Fig. 5. (a) Synthesis of carbazole derivatives and (b) antiproliferative activity test against CHT116 cells and HepG2 cells.
characterize a series of air-stable and water-tolerant organoantimony
(III) perfluoroalkyl(aryl)sulfonate complexes. They exhibited good
thermal stability and relatively strong Lewis acidity. The complexes, as
bifunctional Lewis acidic/basic catalysts, showed high catalytic effi-
ciency, selectivity, and recyclability in the Strecker reaction, Mannich-
type reaction, cross-condensation of aldehydes with ketones, and ami-
nation of epoxides. The butterfly-shaped structure and anion with large
electron-withdrawing ability can significantly improve the stereo-
selectivity and catalytic efficiency for cross-condensation reaction.
Compared with other catalytic systems, complexes exhibited an effi-
cient, mild, highly selective and recyclable protocol for the synthesis of
α-aminonitriles, β-amino carbonyl compounds, chalcones and β-amino-
alcohol. Moreover, we applied such complexes to extend the synthesis of
seven novel carbazole derivatives, which showed good inhibitory ac-
tivity against CHT116 and HepG2 cells. Based on such excellent per-
formance, these complexes had high application potential in organic
synthesis and fine chemicals.
Declaration of Competing Interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
10

N. Li et al.
Molecular Catalysis 511 (2021) 111727
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Acknowledgements
We thank the National Natural Science Foundation of China
(21802093, 21536003), Scientific and Technological Innovation Pro-
grams of Higher Education Institutions in Shanxi (2019L0408), and the
PhD Start-up Foundation of Shanxi Medical University (03201501) for
the financial support. We also thank the helpful discussion of researcher
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11