Synthesis of cis-1,2-diol-type chiral ligands and their dioxaborinane derivatives: Application for the asymmetric transfer hydrogenation of various ketones and biological evaluation

Article abstract of DOI:10.1002/aoc.5835

Two cis-1,2-diol-type chiral ligands (T₁ and T₂) and their tri-coordinated chiral dioxaborinane (T_(1–2)B_(1–2)) and four-coordinated chiral dioxaborinane adducts with 4-tert-butyl pyridine sustained by N → B dati

Full text of DOI:10.1002/aoc.5835

Received: 21 March 2020
DOI: 10.1002/aoc.5835
Revised: 3 May 2020
Accepted: 8 May 2020
F U L L P A P E R
Synthesis of cis-1,2-diol-type chiral ligands and their
dioxaborinane derivatives: Application for the asymmetric
transfer hydrogenation of various ketones and biological
evaluation
1
Ahmet Kilic1
Feyyaz Durap3
| Tugba Ersayan Balci | Nevin Arslan2 | Murat Aydemir3
|
ꢀ
| Veysi Okumus¸4 | Recep Tekin5
1Art and Science Faculty, Chemistry
Department, Harran University, Sanliurfa,
63190, Turkey
2Department of Field Crops, Faculty of
Agriculture, S¸ırnak University, S¸ırnak,
73000, Turkey
3Department of Chemistry, Science
Faculty, Dicle University, Diyarbakir,
21280, Turkey
4Department of Biology, Faculty of
Science and Art, University of Siirt, Siirt,
56100, Turkey
Two cis-1,2-diol-type chiral ligands (T1 and T2) and their tri-coordinated chiral
dioxaborinane (T(1–2)B(1–2)
) and four-coordinated chiral dioxaborinane
adducts with 4-tert-butyl pyridine sustained by N ! B dative bonds
(T(1–2)B(1–2)-N) were synthesized and characterized by various spectroscopic
techniques such as NMR (1H, 13C, and 11B), FT-IR and UV–Vis spectroscopy,
LC–MS/MS, and elemental analysis. It was suggested that both ferrocene and
trifluoromethyl groups played key roles in the catalytic and biological studies
because they could tune the solubility of the chiral dioxaborinane complexes
and adjust the strength of intermolecular interactions. To assess the biological
activities of newly synthesized chiral dioxaborinane compounds, DPPH
(2,2-diphenyl-1-picrylhydrazyl) radical scavenging, reducing power,
antibacterial, DNA binding, and DNA cleavage activities were tested. Then,
all chiral dioxaborinane complexes were investigated as catalysts for the
asymmetric transfer hydrogenation of various ketones under suitable
conditions. The results indicated that the chiral dioxaborinane catalysts
performed well with high yields.
5Department of Infectious Diseases and
Clinical Microbiology, DicleUniversity
Faculty of Medicine, Diyarbakir, 21280,
Turkey
Correspondence
Ahmet Kilic, Harran University,
Chemistry Department, TR-63190
Sanlıurfa, Turkey.
Email: kilica63@harran.edu.tr
K E Y W O R D S
asymmetric transfer hydrogenation, biological activitieschiral dioxaborinanesCis-1,2-diol-type
chiral ligands
1 | INTRODUCTION
attract the tremendous interest in different applications
in the past decade.[1–5] Recent examples are 1:1 Lewis
Boron compounds and their different derivatives are
nowadays widely applied in synthetic chemistry and also
found its way into a wide range of industrial processes
due to unique properties, different chemical structures,
spectroscopic properties, pharmaceutical applications,
and rich history in catalytic chemistry.[1–3] In particular,
various group-functionalized dioxaborinane derivatives
are an important category of boron compounds, which
type spontaneous formation of B ! N bonds formed from
boronic esters and different amines, of which the former
is derived from arylboronic acids and cis-1,2-diol
derivatives.[6,7] This stabilization was attributed to the
relief of ring strain upon the geometry change of boron
center from trigonal planar to tetrahedral due to a single
vacant p orbital and absence of nonbonding electrons,
which at the same time diminishes the reactivity of the
Appl Organomet Chem. 2020;e5835.
wileyonlinelibrary.com/journal/aoc
© 2020 John Wiley & Sons, Ltd.
1 of 19
https://doi.org/10.1002/aoc.5835

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KILIC ET AL.
dioxaborinane ring towards hydrolysis.[6–8] Because of
the aforementioned reasons, starting from relatively sim-
ple reagents, dioxaborinane complexes containing an
N ! B dative bond have successfully been developed
including fluorescence,[9] electrochemical,[10] enzyme-
based sensing,[11] pharmaceutical applications,[12,13] cata-
lytic applications,[14–17] antioxidant and antimicrobial
applications[18–24] etc.
dioxaborinane complexes have been tested for DPPH
(2,2-diphenyl-1-picrylhydrazyl) radical scavenging, reduc-
ing power, antibacterial, DNA binding, and DNA cleav-
age activities. Then, the chiral dioxaborinane complexes
were investigated as catalysts for the transfer hydrogena-
tion of various ketones under suitable conditions.
Based on our expertise in designing boron-containing
compounds as homogeneous catalysts for organic conver-
sions and active compounds for pharmaceutical
studies,[25–28] we have extended our research interests to
the design of stable boron-containing compounds as cata-
lysts for the transfer hydrogenation of various ketones,
and active compounds for biological applications. When
it comes to homogeneous, heterogeneous and/or
organocatalytic systems, previous catalytic studies appear
to focus mostly on transition metal catalysts. In the
recently published catalytic studies, there are many stud-
ies in which main group metal catalysts are used together
with transition metal catalysts. For this purpose, in recent
years, significant advances for developing a wide range of
effective catalytic systems and improvement studies
toward enhancing the selectivity and practicability of the
main group of catalysts, especially boron catalysts, have
been accomplished.[14–17] Besides, main-group elements
(p-block elements) offer great potential since they allow
the activation of various chemical bonds and, conse-
quently enable chemical transformations.[29,30] In addi-
tion, boron-containing compounds have been explored as
inhibitors for different biological targets and some of
them were approved by FDA as the drugs to treat a vari-
ety of diseases such as multiple myeloma, cancer,
etc.[31,32]
Because of their biological potential as antibacterial,
antioxidant and other agents, three-coordinated
dioxaborinane and four-coordinated dioxaborinane com-
plexes containing N ! B dative bonds were found to
exhibit significant biological activities.[33–37] Also, similar
compounds exhibited good cytotoxic effects on skin can-
cer and cervical cancer cells.[38] Therefore, the synthesis
and application of boron compounds containing imine
and other functional groups to biological studies still
attract considerable interest among the scientists since
their medical effects have not been exactly explored. Two
cis-1,2-diol-type chiral ligands and their tri- and four-
coordinated chiral dioxaborinane adducts with 4-tert-
butyl pyridine sustained by N ! B dative bonds success-
fully were synthesized and characterized by various spec-
troscopic techniques such as NMR (1H, 13C, and 11B), FT-
IR and UV–Vis spectroscopy, LC–MS/MS, and elemental
analysis. After the characterization of all compounds, the
cis-1,2-diol-type chiral ligands and their chiral
2 | EXPERIMENTAL
2.1 | General considerations
All chemical solvents, starting materials and other
chemicals used for synthesis were commercially available
and obtained from commercial suppliers were used with-
out any additional purification and any additional chemi-
cal process. For the synthesis of chiral dioxaborinane
derivatives, all reactions requiring a dry atmosphere were
performed under argon (Ar) atmosphere in standard
Dean-Stark techniques. 1H (at 400 MHz) and 13C
(at 100 MHz) NMR-spectra were recorded using an
Agilent Technologies 400 MHz spectrometer in CHCl3 or
DMSO-d6 with TMS as internal standard. 11B NMR spec-
tra were acquired at 192.5 MHz in DMSO-d6 and at 23 ꢀC
temperature. Chemical shifts are given in parts per mil-
lion (ppm). Coupling constants (J values) are given in
Hertz (Hz). The FT-IR spectra were recorded on a
Perkin-Elmer Two UATR-FT spectrophotometer in the
range of 4,000 to 400 cm−1 at 25 C with equipped ATR
ꢀ
accessory. Specific rotations were taken on a Perkin-
Elmer 341 model polarimetry. UV–Vis measurements
were acquired on a Perkin-Elmer model Lambda 25 spec-
trophotometer in the range of 200 to 1,100 nm using qua-
rtz cuvettes at room temperature and C2H5OH with
CHCl3 have been selected as solvents. The mass spectra
(LC–MS) were obtained through using a Shimadzu LC–
MS/MS spectrometer by ESI technique. Elemental analy-
sis was carried out on a Fissions EA 1108 CHNS-O instru-
ment. Thin layer chromatography (TLC) was conducted
on glass plates coated with silica gel. Melting points of all
complexes have been determined in open capillary tubes
on an Electrothermal 9,100 melting point apparatus and
are uncorrected. GC analyses were performed on a
Shimadzu GC 2010 Plus Gas Chromatograph equipped
with cyclodex B (Agilent) capillary column (30 m x
0.32 mm I.D. x 0.25 μm film thickness). Racemic samples
of alcohols were obtained by reduction of the
corresponding ketones with NaBH4 and used as the
authentic samples for ee determination. The GC parame-
ters for asymmetric transfer hydrogenatꢀion of ketones
were as follows; initial temperature, 50 C; initial time
1.1 min; solvent delay, 4.48 min; temperature ramp
1.3 ꢀC/min; final temperature, 150 ꢀC; initial time

KILIC ET AL.
3 of 19
1,115 υ(C-O). 1H-NMR (400 MHz; CHCl3): δ (ppm) = 9.64
(s, 2H, OH), 8.17 (s, 1H, HC=N), 7.23–6.70 (m, 8H, Ar-
CH), 4.41–4.27 (q, 1H, N-CH), and 1.43 (s, 3H, -CH-CH3).
13C-NMR (100 MHz; CHCl3): δ (ppm) = 160.70 (HC=N),
152.32, 145.49, 144.51, 142.44, 140.91, 129.09, 128.69,
128.29, 127.49, 126.08, 125.85, 125.26, and 115.39 (Ar-
ꢀ
2.2 min; temperature ramp 2.15 C/min; final tempera-
ꢀ
ture, 250 C; initial time 3.3 mꢀin; final time, 44.33 min;
injector port temperature, 200 C; detector temperature,
200 ꢀC, injection volume, 2.0 μL.
2.2 | Synthesis of chiral ligands (T1
and T2)
CH), 57.03 (N-CH), and 22.49 (-CH-CH3). UV–Vis (λmax
/
(nm), shoulder peak): 224, 279, 319 and
*
=
409 (C2H5OH); 243, 269, 307, 357* and 412 (CHCl3).
The chiral ligands (T1 and T2) were synthesized as
are given procedure: (1.0 g, 7.24 mmol) of
3,4-Dihydroxybenzaldehyde for chiral ligands (T1 and
T2) was dissolved in methyl alcohol (30 mL) at room
temperature and put into a tri-necked-flask, equipped
with a nitrogen (N2) connection. The mixtures were
warmed and then the (R)-(+)-α-ethyl benzylamine
(1.10 mL, 7.24 mmol) for chiral ligand (T1) and
(R)-(+)-α-methyl benzylamine (0.92 mL, 7.24 mmol) for
chiral ligand (T2) was added to each reaction balloon
in the presence of three drops formic acid as catalyst.
The reaction mixture was heated to reflux temperature
for 6 h with continuous stirring and then the mixture
cooled slowly to room temperature. Solvent was
removed in vacuo yielding a crude oil and the crude
oil was washed three times with diethyl ether with
n-hexane, successively, and crystallized in CH2Cl2/
C2H5OH (1:3) by slow evaporation afforded pure (T1
and T2) chiral ligands.
2.3 | Synthesis of tri-coordinated chiral
dioxaborinane compounds (T(1–2)B [1-2]
)
To a 100 ml round-bottom flask with a nitrogen (N2) con-
nection, chiral ligands (T1) (0.32 g, 1.24 mmol) with (T2)
(0.30 g, 1.24 mmol) and corresponding ferrocene boronic
acid (0.29 g, 1.24 mmol) for dioxaborinane compounds
(T1B1 and T2B1), and 3,5-Bis (trifluoromethyl)phenyl
boronic acid (0.33 g, 1.24 mmol) for dioxaborinane com-
pounds (T1B2 and T2B2), respectively, in toluene (70 ml)
were stirred under reflux conditions for 24 hr using a
Dean-Stark condenser in order to remove the water by-
product. Then, the mixtures were cooled slowly to room
temperature and these mixtures were stirred at room
temperature for 12 hr. Within this time a colored precipi-
tate appeared and kept standing overnight. The solvent
was removed under reduced pressure. The residue was
washed three times with 5 ml of n-hexane and diethyl
ether and crystallized in CH2Cl2/C2H5OH (1:3) by slow
evaporation. TLC analysis showed a single well-defined
peak for tri-coordinated chiral dioxaborinane compounds
(T(1–2)B(1–2)).
T1: Yield: 1.89 g (86%), M.p. = 109 ꢀC, Elemental
Analysis (calculated for C16H17NO2) (F.W: 255.3 g/mol)
(%): C, 75.27; H, 6.71; N, 5.49. Found: C, 75.24; H,
6.67; N, 5.54. LC–MS/MS (Scan ES+): m/z = 256.1
[M + H]+. FT-IR (ATR, υmax-cm−1): 3448–2,381 υ(O-
H····OH), 3,062 and 3,032 υ (Ar-CH), 2,968–2,877
υ (Aliph-CH), 1,660 υ(C=N), 1,567–1,454 υ(C=C), and
1,114 υ(C-O). 1H-NMR (400 MHz; CHCl3): δ (ppm) = 9.65
(s, 2H, OH), 8.13 (s, 1H, HC=N), 7.49–6.71 (m, 8H, Ar-
CH), 4.08 (t, 1H, J = 6.4 Hz, N-CH), 1.84–1.61 (m, 2H,
-CH-CH2), and 0.76 (t, 3H, J = 5.4 Hz, -CH2-CH3). 13C-
NMR (100 MHz; CHCl3): δ (ppm) = 161.00 (HC=N),
152.17, 145.44, 141.38, 139.88, 129.16, 129.08, 128.87,
128.66, 128.53, 128.30, 127.96, 127.91, 127.77, 127.47,
127.23, 126.60, 126.55, 126.17, and 115.39 (Ar-CH), 64.35
(N-CH), 29.03 (-CH-CH2), and 10.63 (-CH2-CH3). UV–Vis
(λmax/(nm), * = shoulder peak): 230, 277, 318 and
408 (C2H5OH); 242, 268, 305, 359* and 413 (CHCl3).
T2: Yield: 1.45 g (83%), M.p. = 114 ꢀC, Elemental
Analysis (calculated for C16H17NO2) (F.W: 241.1 g/mol)
(%): C, 74.67; H, 6.27; N, 5.81. Found: C, 74.62;
H, 6.24; N, 5.77. LC–MS/MS (Scan ES+): m/z = 242.1
ꢀ
T1B1: Yield: 0.42 g (74%), M.p. = 141 C, Elemental
Analysis (calculated for C26H24BFeNO2) (F.W:
449.1 g/mol) (%): C, 69.53; H, 5.39; N, 3.12. Found: C,
69.49; H, 5.35; N, 3.08. LC–MS/MS (Scan ES+):
m/z = 450.1 [M + H]+. FT-IR (ATR, υmax-cm−1): FT-IR
(ATR, υmax-cm−1): 3205 υ (Fer C-H), 3,089 and 3,029
υ (Ar-CH), 2,974–2,880 υ (Aliph-CH), 1,649 υ(C=N),
1,539–1,456 υ(C=C), 1,382 υ (Fer C-C), 1,263 υ(B-O),
1
1,109 υ(C-O), 817 υ(B-C) and 477 υ (Fer Fe-C). H-NMR
(400 MHz; DMSO-d6): δ (ppm) = 8.28 (s, 1H, HC=N),
7.58–6.74 (m, 8H, Ar-CH), 4.48 (s, 1H, N-CH), 4.30 (s,
2H, Fer-CH), 4.16 (s, 2H, Fer-CH), 4.04 (s, 5H, Fer-CH),
2.18–1.89 (m, 2H, -CH-CH2), and 0.88 (t, 3H, J = 5.4 Hz,
-CH2-CH3). 13C-NMR (100 MHz; DMSO-d6):
δ
(ppm) = 158.21 (HC=N), 152.34, 143.85, 138.05, 137.82,
129.39, 129.26, 128.70, 128.28, 128.14, 127.86, 127.59,
127.25, 126.91, 125.81, 108.47, and 105.73 (Ar-CH), 73.90,
71.59, 68.60, and 68.23 (Fer-CH), 56.69 (N-CH), 29.69
(-CH-CH2), and 11.30 (-CH2-CH3). 11B NMR (DMSO-d6,
192.5 MHz, 23 ꢀC, δ ppm): 31.43. UV–Vis (λmax/(nm),
[M
+ υ
H]+. FT-IR (ATR, max-cm−1): 3443–2,375
υ(O-H····OH), 3,059 and 3,031 υ (Ar-CH), 2,979–2,872
υ (Aliph-CH), 1,661 υ(C=N), 1,569–1,448 υ(C=C), and

4 of 19
KILIC ET AL.
* = shoulder peak): 218, 237*, 322 and 362 (C2H5OH);
244, 269*, 305, and 329 (CHCl3).
(ppm) = 160.78 (HC=N), 154.33, 141.26, 139.69, 137.92,
134.73, 132.11, 130.31, 129.98, 129.20, 128.65, 127.73,
127.39, 127.16, 126.84, 123.87, 122.74, 120.03, 119.47,
116.36, 115.96, 114.84, 109.33, 108.27, 105.69, and 105.29
(Ar-CH), 125.45 (-CF3), 56.25 (N-CH), and 27.89 (-CH-
CH3). B NMR (DMSO-d6, 192.5 MHz, 23 C, δ ppm):
29.85. UV–Vis (λmax/(nm), * = shoulder peak): 221, 246*,
289, 332, 399, and 527* (C2H5OH); 245, 331, 406, and
523* (CHCl3).
ꢀ
T2B1: Yield: 0.38 g (70%), M.p. = 100 C, Elemental
Analysis (calculated for C25H22BFeNO2) (F.W:
435.1 g/mol) (%): C, 69.01; H, 5.10; N, 3.32. Found: C,
68.97; H, 5.07; N, 3.28. LC–MS/MS (Scan ES+):
m/z = 435.2 [M]+. FT-IR (ATR, υmax-cm−1): 3208 υ (Fer
C-H), 3,062 and 3,028 υ (Ar-CH), 2,982–2,877 υ (Aliph-
CH), 1,646 υ(C=N), 1,559–1,489 υ(C=C), 1,380 υ (Fer C-
C), 1,261 υ(B-O), 1,109 υ(C-O), 819 υ(B-C) and 480 υ (Fer
11
ꢀ
1
Fe-C). H-NMR (400 MHz; DMSO-d6): δ (ppm) = 8.31 (s,
1H, HC=N), 7.45–6.53 (m, 8H, Ar-CH), 4.45 (s, 1H, N-
CH), 4.29 (s, 2H, Fer-CH), 4.17 (s, 2H, Fer-CH), 4.07 (s,
5H, Fer-CH), and 1.05 (s, 3H, -CH-CH3). 13C-NMR
(100 MHz; DMSO-d6): δ (ppm) = 158.44 (HC=N), 152.27,
142.12, 139.61, 129.21, 129.11, 128.94, 128.74, 128.57,
128.34, 127.61, 127.15, 126.96, 126.49, 126.38, 108.39, and
105.67 (Ar-CH), 73.83, 71.50, 68.53, and 68.16 (Fer-CH),
56.47 (N-CH), and 20.05 (-CH-CH3), 11B NMR (DMSO-d6,
192.5 MHz, 23 ꢀC, δ ppm): 30.78. UV–Vis (λmax/(nm),
* = shoulder peak): 220, 258*, 323 and 410 (C2H5OH);
246, 329, and 417* (CHCl3).
2.4 | Synthesis of four-coordinated chiral
dioxaborinane compounds (T(1–2)B(1–2)-N)
To a 100 ml round-bottom flask, a CH2Cl2 solution
(40 ml) of compound (T1B1) (0.30 g, 0.67 mmol), com-
pound (T2B1) (0.29 g, 0.67 mmol), compound (T1B2)
(0.32 g, 0.67 mmol) and compound (T2B2) (0.31 g,
0.67 mmol) was slowly added to a mixture of 4-tert-butyl
pyridine (1.0 ml, 0.67 mmol) in CH2Cl2 (10 ml) at room
temperature, respectively and the mixtures were stirred
under room temperature for 24 hr. Follow by, the solvent
was removed under vacuum evaporator and the obtained
crystals was washed three times with 5 ml of n-hexane
and crystallized in CHCl3/C2H5OH (1:3) by slow evapora-
tion. TLC analysis showed a single well-defined peak for
four-coordinated chiral dioxaborinane compounds
(T(1–2)B(1–2)-N). The different spectral results allows
assignment to the known 4-tert-butyl pyridine adduct of
tri-coordinated chiral dioxaborinane compounds and tri-
ꢀ
T1B2: Yield: 0.42 g (71%), M.p. = 105 C, Elemental
Analysis (calculated for C24H18BF6NO2) (F.W:
477.1 g/mol) (%): C, 60.41; H, 3.80; N, 2.94. Found: C,
60.39; H, 3.76; N, 2.90. LC–MS/MS (Scan ES+):
m/z = 478.2 [M + H]+. FT-IR (ATR, υmax-cm−1): 3067
and 3,040 υ (Ar-CH), 2,974–2,882 υ (Aliph-CH), 1,643
υ(C=N), 1,569–1,457 υ(C=C), 1,264 υ(B-O), 1,120 υ(C-O)
and 819 υ(B-C). 1H-NMR (400 MHz; DMSO-d6): δ
(ppm) = 8.68 (s, 1H, HC=N), 8.37–7.14 (m, 11H, Ar-CH),
4.10 (t, 1H, J = 5.8 Hz, N-CH), 1.93–1.64 (m, 2H, -CH-
CH2), and 0.85 (t, 3H, J = 5.4 Hz, -CH2-CH3). 13C-NMR
(100 MHz; DMSO-d6): δ (ppm) = 160.77 (HC=N), 154.33,
141.27, 139.70, 137.93, 134.75, 131.79, 129.98, 129.22,
128.66, 127.74, 127.40, 126.83, 123.91, 122.75, 120.03,
116.56, 115.96, 107.91, and 106.19 (Ar-CH), 125.45 (-CF3),
57.35 (N-CH), 27.90 (-CH-CH2), and 11.14 (-CH2-CH3).
coordinated
chiral
dioxaborinane
compounds
(T(1–2)B(1–2)) then converted into the corresponding four-
coordinated
chiral
dioxaborinane
compounds
(T(1–2)B(1–2)-N).
T1B1-N: Yield: 0.32 g (82%), M.p. = 230 ꢀC, Elemental
Analysis (calculated for C35H37BFeN2O2) (F.W:
584.3 g/mol) (%): C, 71.94; H, 6.38; N, 4.79. Found: C,
71.91; H, 6.34; N, 4.72. LC–MS/MS (Scan ES+):
m/z = 584.3 [M + H]+. FT-IR (ATR, υmax-cm−1): FT-IR
(ATR, υmax-cm−1): 3221 υ (Fer C-H), 3,062 and 3,031
υ (Ar-CH), 2,968–2,871 υ (Aliph-CH), 1,643 υ(C=N),
1,566–1,451 υ(C=C), 1,365 υ (Fer C-C), 1,274 υ(B-O),
11
ꢀ
B NMR (DMSO-d6, 192.5 MHz, 23 C, δ ppm): 32.43.
UV–Vis (λmax/(nm), * = shoulder peak): 221, 241*,
285, 334, 401, and 524* (C2H5OH); 244, 264, 331, 410,
and 518* (CHCl3).
1
ꢀ
T2B2: Yield: 0.42 g (73%), M.p. = 114 C, Elemental
1,104 υ(C-O), 819 υ(B-C) and 483 υ (Fer Fe-C). H-NMR
Analysis (calculated for C23H16BF6NO2) (F.W:
463.1 g/mol) (%): C, 59.64; H, 3.48; N, 3.02. Found: C,
59.60; H, 3.44; N, 2.96. LC–MS/MS (Scan ES+):
m/z = 464.2 [M + H]+. FT-IR (ATR, υmax-cm−1): 3070
and 3,029 υ (Ar-CH), 2,984–2,869 υ (Aliph-CH), 1,644
υ(C=N), 1,575–1,453 υ(C=C), 1,266 υ(B-O), 1,123 υ(C-O)
and 820 υ(B-C). 1H-NMR (400 MHz; DMSO-d6): δ
(ppm) = 8.69 (s, 1H, HC=N), 8.37–7.31 (m, 11H, Ar-CH),
4.76–4.69 (q, 1H, N-CH), and 0.80 (d, 3H, J = 6.4 Hz,
(400 MHz; DMSO-d6): δ (ppm) = 8.17 (s, 1H, HC=N),
7.68–6.96 (m, 12H, Ar-CH), 4.41 (s, 1H, N-CH), 4.28 (s,
2H, Fer-CH), 4.13 (s, 2H, Fer-CH), 4.04 (s, 5H, Fer-CH),
1.81–1.59 (m, 2H, -CH-CH2), 1.24 (s, 9H, t-BuPy-CH3),
and 1.02 (s, 3H, -CH2-CH3). 13C-NMR (100 MHz; DMSO-
d6): δ (ppm) = 159.79 (HC=N), 149.21, 138.09, 134.77,
132.98, 131.71, 129.11, 129.08, 128.99, 128.87, 128.67,
128.29, 127.80, 127.48, 127.13, 126.84, 125.42, 123.97,
122.76, 120.99, 111.45, and 106.20 (Ar-CH), 73.83, 71.49,
68.52, 68.33, (Fer-CH), 56.12 (N-CH), 34.48 (t-BuPy-C-
-CH-CH3). 13C-NMR (100 MHz; DMSO-d6):
δ

KILIC ET AL.
5 of 19
CH3), 30.65 (t-BuPy-C-CH3), 29.46 (-CH-CH2), and 11.29
υ(C=N), 1,574–1,454 υ(C=C), 1,262 υ(B-O), 1,121 υ(C-O)
and 817 υ(B-C). 1H-NMR (400 MHz; DMSO-d6): δ
(ppm) = 8.65 (s, 1H, HC=N), 8.77–7.21 (m, 15H, Ar-CH),
5.11–4.77 (q, 1H, N-CH), 1.24 (s, 9H, t-BuPy-CH3), and
0.81 (s, 3H, -CH-CH3). 13C-NMR (100 MHz; DMSO-d6): δ
(ppm) = 160.48 (HC=N), 153.48, 149.21, 142.07, 140.85,
139.55, 134.76, 131.74, 129.32, 129.11, 128.95, 128.73,
128.68, 128.28, 128.04, 127.18, 127.12, 127.04, 126.63,
126.46, 126.34, 123.96, 122.75, 121.47, 116.37, and 115.95
(Ar-CH), 125.46 (-CF3), 57.01 (N-CH), 34.97 (t-BuPy-C-
CH3), 30.52 (t-BuPy-C-CH3), and 21.10 (-CH-CH3). 11B
11
ꢀ
(-CH2-CH3). B NMR (DMSO-d6, 192.5 MHz, 23 C, δ
ppm): 14.78. UV–Vis (λmax/(nm), * = shoulder peak):
221, 254*, and 334 (C2H5OH); 248 and 346 (CHCl3).
T2B1-N: Yield: 0.32 g (84%), M.p. = 298 ꢀC, Elemental
Analysis (calculated for C25H22BFeN2O2) (F.W:
570.3 g/mol) (%): C, 71.60; H, 6.19; N, 4.91. Found: C,
71.56; H, 6.15; N, 4.87. LC–MS/MS (Scan ES+):
m/z = 570.4 [M]+. FT-IR (ATR, υmax-cm−1): 3216 υ (Fer
C-H), 3,058 and 3,031 υ (Ar-CH), 2,971–2,869 υ (Aliph-
CH), 1,646 υ(C=N), 1,548–1,451 υ(C=C), 1,378 υ (Fer C-
C), 1,263 υ(B-O), 1,104 υ(C-O), 817 υ(B-C) and 486 υ (Fer
ꢀ
NMR (DMSO-d6, 192.5 MHz, 23 C, δ ppm): 14.55. UV–
Vis (λmax/(nm), * = shoulder peak): 219, 284, 330, 402,
1
Fe-C). H-NMR (400 MHz; DMSO-d6): δ (ppm) = 8.47 (s,
1H, HC=N), 7.60–6.71 (m, 12H, Ar-CH), 4.41 (s, 1H, N-
CH), 4.26 (s, 2H, Fer-CH), 4.13 (s, 2H, Fer-CH), 4.04 (s,
5H, Fer-CH), and 1.24 (s, 9H, t-BuPy-CH3), 1.03 (s, 3H,
and 524* (C2H5OH); 241, 326, 408, and 521* (CHCl3).
-CH-CH3). 13C-NMR (100 MHz; DMSO-d6):
δ
2.5 | Catalytic transfer hydrogenation
(ppm) = 159.58 (HC=N), 158.47, 152.29, 152.10, 142.19,
140.22, 139.75, 129.22, 129.02, 128.75, 128.30, 126.94,
126.41, 125.97, 108.40, and 105.68 (Ar-CH), 73.85, 71.52,
68.55, and 68.18 (Fer-CH), 53.87 (N-CH), 34.90 (t-BuPy-
C-CH3), 30.65 (t-BuPy-C-CH3), and 22.21 (-CH-CH3). 11B
NMR (DMSO-d6, 192.5 MHz, 23 C, δ ppm): 14.97. UV–
Vis (λmax/(nm), * = shoulder peak): 234, 256, 283*, and
321 (C2H5OH); 245, 325, and 358* (CHCl3).
General procedure for the catalytic hydrogen-transfer
reaction is given below: A solution of tri or four coordi-
nated chiral dioxaborinane complexes (0.005 mmol),
NaOH (0.025 mmol) and the corresponding ketone
(0.5 mmol) in degassed iso-PrOH (5.0 ml) was refluxed
until the reaction completed. Then, a sample of the reac-
tion mixture is taken off, diluted with acetone, and ana-
lyzed immediately by GC; conversions obtained are
related to the residual unreacted ketone.
ꢀ
T1B2-N: Yield: 0.35 g (86%), M.p. = 140 ꢀC, Elemental
Analysis (calculated for C24H18BF6N2O2) (F.W:
612.4 g/mol) (%): C, 64.72; H, 5.10; N, 4.57. Found: C,
64.69; H, 5.06; N, 4.51. LC–MS/MS (Scan ES+):
m/z = 613.4 [M + H]+. FT-IR (ATR, υmax-cm−1): 3064
and 3,032 υ (Ar-CH), 2,973–2,878 υ (Aliph-CH), 1,638
υ(C=N), 1,575–1,458 υ(C=C), 1,265 υ(B-O), 1,118 υ(C-O)
and 818 υ(B-C). 1H-NMR (400 MHz; DMSO-d6): δ
(ppm) = 8.69 (s, 1H, HC=N), 8.48–7.27 (m, 15H, Ar-CH),
4.16 (t, 1H, J = 5.4 Hz, N-CH), 2.04–1.68 (m, 2H, -CH-
CH2), 1.22 (s, 9H, t-BuPy-CH3), and 0.79 (t, 3H,
J = 5.4 Hz, -CH2-CH3). 13C-NMR (100 MHz; DMSO-d6): δ
(ppm) = 160.77 (HC=N), 149.29, 138.03, 134.74, 132.08,
131.76, 129.98, 129.66, 129.31, 129.16, 129.04, 128.99,
128.95, 128.82, 128.66, 128.29, 127.80, 127.43, 127.17,
126.98, 126.84, 126.71, 123.91, 122.75, 121.39, 116.35 and
109.30 (Ar-CH), 125.45 (-CF3), 56.25 (N-CH), 34.93 (t-
BuPy-C-CH3), 30.54 (t-BuPy-C-CH3), 27.90 (-CH-CH2),
and 11.16 (-CH2-CH3). 11B NMR (DMSO-d6, 192.5 MHz,
2.6 | Biological assays
2.6.1 | DPPH radical scavenging activity
The stock solutions of the chiral dioxaborinane com-
plexes were diluted in DMSO to a final concentration of
25–200 μg/ml. Methanol solution of 2.0 ml DPPH was
added to 0.5 ml test complexes in different concentrations
of dimethyl sulfoxide (DMSO) and incubated at room
temperature for 40 min in the dark. After the incubation
time, the absorbance of the solution was measured at
517 nm. Trolox was used as a reference standard sub-
stance to evaluate complexes.[39]
ꢀ
23 C, δ ppm): 14.52. UV–Vis (λmax/(nm), * = shoulder
2.6.2 | Reducing power activity
peak): 223, 251*, 330, 397 and 523* (C2H5OH); 242, 327,
404 and 513* (CHCl3).
The reducing power activity of the chiral dioxaborinane
complexes was tested by the method of Oyaizu[40] with
minor modifications. The stock solutions of the chiral
dioxaborinane complexes were diluted to the working
range concentrations (25–200 μg/ml) in DMSO and activ-
ity was determined at 700 nm. α-tocopherol was used as a
standard.
T2B2-N: Yield: 0.33 g (83%), M.p. = 120 ꢀC, Elemental
Analysis (calculated for C32H29BF6N2O2) (F.W:
598.4 g/mol) (%): C, 64.23; H, 4.89; N, 4.68. Found: C,
64.19; H, 4.84; N, 4.61. LC–MS/MS (Scan ES+):
m/z = 599.4 [M + H]+. FT-IR (ATR, υmax-cm−1): 3064
and 3,032 υ (Ar-CH), 2,974–2,871 υ (Aliph-CH), 1,636

6 of 19
KILIC ET AL.
2.6.3 | Antibacterial activity
(R)-(+)-α-ethyl
benzylamine
or
(R)-(+)-α-methyl
benzylamine in methyl alcohol under reflux temperature
with a yield in the range 86–83% in the presence of three
drops of formic acid as catalyst, as shown in Scheme 1.
After crystallization and full characterization of the chiral
ligands (T1 and T2), they were employed in the synthesis
of the respective novel tri-coordinated chiral
dioxaborinane complexes (T(1–2)B(1–2)) in toluene under
reflux conditions for 24 hr with a yield up to 74% (see
Scheme 2) using a Dean-Stark condenser to remove the
water by-product. Subsequently, as shown in Scheme 3,
the four-coordinated chiral dioxaborinane compounds
(T(1–2)B(1–2)-N), in which the boron is four-coordinated
due to chelation by 4-tert-butyl pyridine group, were syn-
thesized in CH2Cl2 at room temperature over 24 hr with
a good yield in the range 86–82%. The novel tri-
coordinated chiral dioxaborinane (T(1–2)B(1–2)) and four-
Antibacterial activity of the chiral dioxaborinane complexes
was tested according to Khan and Asiri.[41] Stock solutions
of the compounds were prepared in DMSO at a concentra-
tion of 500 μg/ml. 15 μL of compounds impregnated into
sterile antibiotic discs and each disc was placed in a petri
dish with nutrient agar inoculated with bacteria. Pseudomo-
nas aeruginosa (ATCC 9027), Escherichia coli (ATCC
10536) and Legionella pneumophila subsp. pneumophiia
(ATCC 33152) were used as Gram-negative bacteria and
Enterococcus hirae (ATCC 10541), Staphylococcus aureus
(ATCC 6538) and Bacillus cereus were used as test
microorganisms. Streptomycin (10 μg) and Tetracycline
(30 μg) were used as reference standard antibiotics.
2.6.4 | DNA binding and DNA cleavage
activities
coordinated
chiral
dioxaborinane
complexes
(T(1–2)B(1–2)-N), in which boron is four-coordinated due
to chelation by 4-tert-butyl pyridine group, were designed
for spectroscopic and catalytic study as well as antimicro-
bial activities and antioxidant studies. The formed four-
coordination bonds with 4-tert-butyl pyridine nucleo-
philes as well as covalent B-O and B-N bonds make the
structure stable in air. The formation of the two cis-1,-
2-diol-type chiral ligands (T1 and T2) and their tri-
DNA binding and DNA cleavage activities of the chiral
dioxaborinane complexes were performed using agarose
gel electrophoresis according to the method of Meriç
et al.[42] The complexes prepared at 200 μg/ml in DMSO
were incubated for 8 hr at 37 ꢀC with CT-DNA at 2 μg/ml
concentrations and pBR322 DNA at 0.1 μg/ml concentra-
tions. Then, the samples were loaded on 1% agarose gel
containing 8 μl 0.05% ethidium bromide, followed by dis-
playing under UV light and photographing.
coordinated
chiral
dioxaborinane
compounds
(T(1–2)B(1–2)) and four-coordinated chiral dioxaborinane
compounds (T(1–2)B(1–2)-N), in which boron is four-
coordinated due to chelation by 4-tert-butyl pyridine
group, were fully characterized using several spectro-
scopic and analytical techniques such as NMR (1H, 13C,
and 11B), FT-IR, and UV–Vis spectroscopy, LC–MS/MS,
and elemental analysis. Attempts to grow crystals of the
cis-1,2-diol-type chiral ligands (T1 and T2) and their
tri-coordinated chiral dioxaborinane (T(1–2)B(1–2)) and
3 | RESULTS AND DISCUSSION
3.1 | Synthesis and characterization
Initially, two novel chiral ligands (T1 and T2) were
obtained
from
3,4-dihydroxybenzaldehyde
and
SCHEME 1 Synthesis
route of proposed chiral ligands
(T1 and T2)

KILIC ET AL.
7 of 19
SCHEME 2 Synthesis of
proposed tri-coordinated chiral
dioxaborinane compounds
(T(1–2)B(1–2)
)
SCHEME 3 Structure of
proposed four-coordinated chiral
dioxaborinane compounds
(T(1–2)B(1–2)-N)
four-coordinated chiral dioxaborinane complexes
(T(1–2)B(1–2)-N) suitable for single-crystal XRD were not
successful. However, the spectroscopic and analytical
results of all compounds are consistent with the proposed
structure. Also, all compounds were isolated as a powder
that is air-stable in the solid-state and all compounds

8 of 19
KILIC ET AL.
were followed by TLC, which revealed that the com-
pounds were sufficiently pure. Also, CHN elemental
analysis supported purity of the compounds.
benzene ring. The following the n ! π* transition of
non-bonded electrons of imine (C=N) groups or π-to-
vacant B p-orbital transition was observed in the range
357–527 nm in C2H5OH or CHCl3, respectively.[47]
The NMR (1H, 13C, and 11B) spectral data were in
good agreement with the proposed structures in CDCl3 or
DMSO-d6 (Figure S1-S16 in the ESI). The major differ-
ence between the 1H NMR spectra of ligands (T1 and T2)
and their complexes (T(1–2)B(1–2)) and (T(1–2)B(1–2)-N) is
the presence of a new signal for the boronic acid groups
and 4-tert-butyl pyridine (Figure S1-S10 in the ESI). In 1H
NMR spectra, the disappearance of a singlet at 9.65 and
9.64 ppm for (T1) and (T2), respectively, which belong to
-OH group of the cis-1,2-diol, is the indication for the
deprotonation of hydroxyl and formation of the desired
chiral dioxaborinane complexes, as expected.[15,48,49] The
characteristic resonance of the azomethine (CH=N) pro-
tons shifted from 8.13 and 8.17 ppm for (T1) and (T2),
respectively, to 8.69–8.17 ppm in the chiral dioxaborinane
complexes, indicating the formation of the complexes, as
observed elsewhere.[50] Furthermore, the ferrocene
region can show three signals in the range of
3.2 | Spectroscopic studies
FT-IR spectroscopy was used as a characteristic tech-
nique to elucidate structures of cis-1,2-diol-type chiral
ligands (T1 and T2) and their chiral dioxaborinane deriv-
atives (T(1–2)B(1–2)) and (T(1–2)B(1–2)-N), FT-IR spectral
data of which are given in the experimental part. In the
FT-IR spectra of (T(1–2)B(1–2)) and (T(1–2)B(1–2)-N), a
broad band of the ligands in the range of
3,448–2,334 cm−1, which corresponded to the cis-1,2-diol
υ(O-H····OH), completely disappeared. Other characteris-
tic bands appeared at approximately 1,660 cm−1 corre-
spond to the stretching vibrations of imine υ(C=N) group
of chiral ligands (T1 and T2), whereas the imine υ(C=N)
stretching vibrations of complexes (T(1–2)B(1–2)) and
(T(1–2)B(1–2)-N) appeared in the range of 1,649–1,643 and
1,646–1,636 cm−1, respectively.[16,43–45] Moreover, the
two new characteristic peaks in the range of 1,274–1,261
and 820–817 cm−1 correspond to the stretching vibrations
of υ(B-O) and υ(B-C) groups of chiral dioxaborinane
derivatives (T(1–2)B(1–2)) and (T(1–2)B(1–2)-N), respec-
tively.[26,46] Furthermore, two peaks observed in the
range of 1,382–1,365 and 486–480 cm−1, which could be
attributed to ferrocene υ(C-C) and υ (Fe-C) stretchings in
the framework of chiral dioxaborinane complexes,
respectively.Electronic transitions of ligands (T1 and T2)
4.30–4.04
ppm
due
to
the
non-substituted
cyclopentadiene of ferrocene-based chiral dioxaborinane
(T(1–2)B1) and (T(1–2)B1-N) derivatives.[51] Moreover, the
13C NMR spectra can be analyzed analogously to that of
the proton spectra and the resonances in the 13C NMR
spectra support the formation of the ligands and their
chiral dioxaborinane complexes (Figure S1-S10 in the
ESI). In the 13C NMR spectra, the signal of the imine car-
bon (CH=N) shifted after coordination to boron center
from 161.00–160.70 ppm in ligands (T1 and T2) to
160.78–158.21 ppm in complexes (T(1–2)B(1–2)) and
160.77–159.58 in (T(1–2)B(1–2)-N). These results clearly
show that the free ligands bound to the boron center in
the chiral dioxaborinane complexes and the noticeable
shift is observed for the (CH=N) resonance due to com-
plexation, as expected. Specifically, in the 13C NMR spec-
tra of the ferrocene-based chiral dioxaborinane
complexes (T(1–2)B1) and (T(1–2)B1-N), the carbon sig-
nals of ferrocene unit were observed at range
73.90–68.16 ppm, confirming that two cyclopentadiene
ring containing the ferrocene unit bound to boron cen-
ter.[15] The other characteristic carbon resonances for the
compounds were observed in the expected values, which
is another evidence of the formation of the proposed
structures. The 11B NMR data also supports the formation
of the chiral dioxaborinane complexes (Figures 1, 2 and
S11–16 in the ESI). The 11B NMR spectra are of special
interest because the signal in the 11B NMR spectra gives a
strong indication of whether the complexes formed or
not. As expected, the 11B NMR spectra of tri-coordinated
and their chiral dioxaborinane (T(1–2)B(1–2)
)
and
(T(1–2)B(1–2)-N) complexes were studied in C2H5OH and
CHCl3 (2.10−6–2.10−8 M) at room temperature and
recorded at λmax as nm. The UV–Vis spectral data of all
chiral compounds are given in Figure S17–22 and the
experimental section. The chiral ligands and their boron
complexes typically display a λmax value of between
218 and 527 nm in their UV–Vis absorption spectra due
to π ! π*, n ! π* transition of non-bonded electrons or
π-to-vacant B p-orbital transitions. Besides, some specific
transitions of π ! π* and n ! π* were observed in the
range of 224–413 nm in C2H5OH or CHCl3, respectively,
for ligands (T1 and T2) with little shift after bonding to
the boron center. Additionally, in the electronic spectra
of chiral dioxaborinane (T(1–2)B(1–2)) and (T(1–2)B(1–2)
-
N) complexes, the strong broad absorption bands in the
range 218–527 nm in C2H5OH or CHCl3 can be attributed
to the π ! π*, n ! π* transition of non-bonded electrons
or π-to-vacant B p-orbital transitions.[47] In view of the
this results, the strong broad absorption bands in the
range 218–346 nm in C2H5OH or CHCl3, respectively,
can be attributed to the π ! π* transitions of aromatic
chiral dioxaborinanes (T(1–2)B(1–2)
)
in DMSO-d6

KILIC ET AL.
9 of 19
FIGURE 1 11B NMR spectrum of chiral
dioxaborinane (T1B1)
FIGURE 2 11B NMR spectrum of chiral
dioxaborinane (T1B1-N)
exhibited only broad singlet signals in the range of
32.43–29.85 ppm for the trigonal geometry due to the
similar chemical environment for the boron center of
each chiral dioxaborinane complexes. On the other hand,
the 11B NMR spectra of four-coordinated chiral
dioxaborinanes (T(1–2)B(1–2)-N) showed only broad sin-
glet resonances in the range of 14.97–14.52 ppm, which
shifts upfield compared to the tri-coordinated chiral
dioxaborinanes (T(1–2)B(1–2)) because the boron atom
completely adopts a tetrahedral configuration upon asso-
ciating with 4-tert-butyl pyridine.
chiral dioxaborinane complexes. The LC–MS/MS spectra
of ligands (T1 and T2) exhibit the ion peaks at
m/z = 256.10 and 242.10 amu [M + H]+ for (T1) and
(T2), respectively. On the other hand, the chiral
dioxaborinanes
complexes
(T(1–2)B(1–2)
)
and
(T(1–2)B(1–2)-N) show characteristic base peaks for the
chiral dioxaborinane as [M + H]+ or as [M]+ and
expected values.
3.3 | Catalytic performances of chiral
Further confirmation for the formation of ligands (T1
and T2) and their chiral dioxaborinane complexes
(T(1–2)B(1–2)) and (T(1–2)B(1–2)-N) comes from LC–
MS/MS (Figure 3-5 and S23-S29 in the ESI). The LC–
MS/MS spectra showed the expected molecular and frag-
mentation ions, with appropriate isotope distribution.
The isotopic distribution of parent ions in the spectra
demonstrated the presence of one boron atom in the
dioxaborinane compounds
Nowadays, several transition metals such as Ir, Rh and
Ru are often used as catalysts in transfer hydrogenation
with high activity.[52–55] Instead of them; the develop-
ment of the effective and cheaper catalytst for transfer
hydrogenation of ketones is one of the main targets for
the scientists, there have been continuous studies to

10 of 19
KILIC ET AL.
FIGURE 3 LC–MS/MS spectrum of chiral ligand (T2)
FIGURE 4 LC–MS/MS spectrum of dioxaborinane compound (T2B1)

KILIC ET AL.
11 of 19
FIGURE 5 LC–MS/MS spectrum of chiral dioxaborinane compound (T2B1-N)
explore new metals for transfer hydrogenation reactions.
In this study, we focused the use of boron metal for trans-
fer hydrogenation. The asymmetric transfer hydrogena-
tion (ATH) of ketones was studied with dioxaborinanes
(T(1–2)B(1–2)) and (T(1–2)B(1–2)-N) as catalysts. In our ini-
tial experiment, acetophenone was used as a model sub-
strate for the asymmetric transfer hydrogenation (ATH)
and results of optimization studies were tabulated in
Table 1. The optimization reactions were carried out
under anaerobic conditions. Initially, we have taken
acetophenone (0.5 mmol), iso-PrOH (5 ml) as the H-
donor, NaOH (0.025 mmol) as the base and catalyst
(0.005 mmol) at room temperature and stirred for 72 hr
which results in lower conversions (Table 1, Entry 1–8).
Due to the reversibility at room temperature, prolonging
β-elimination to afford ruthenium hydride, which is an
active species in this reaction. This is the mechanism pro-
posed by several research groups on the studies of
ruthenium-catalyzed transfer hydrogenation reaction by
metal hydride intermediates.[56–62] Boron-catalyzed
mechanism is thought to be like this mechanism. The
highest conversions were obtained when reactions were
performed with a base at reflux temperature using cata-
lysts T1B2 and T1B2-N for 48 and 24 hr, respectively, as
seen in Table 1, entry 17–24. Furthermore, we found that
catalytic activity of complex T1B1 and T2B1, which is only
one methylene moiety different, is similar at the same
temperature for the same reaction time (Entry 17–18).
Moreover, substitution of 3,5-bis (trifluoromethyl)phenyl
moiety (T1B2 and T2B2) with ferrocene group does not
cause any change in conversion, while slight change in
enantioselectivity occurred (Entry 19–20). However, the
coordination of 4-tert-butylpyridine to the boron atom
led to an increase in both the reaction rate and
enentioselectivity (Entry 21–24). In addition, there was
no significant change in the conversion and
enantioselectivity when KOH was used instead of NaOH
(entry 17–18). Next, ratio of the base was changed from
100:1:3 to 100:1:9, and the highest conversion and
the reaction time led to
a
slight decrease in
enantioselectivity (entries 1 and 2,[d]).[52–54] The next
reaction was carried out without base and refluxed for
48 hr (Table 1, Entry 9–16) which results in no product
formation. This indicates that the presence of a base is
essential to carry out this reaction. In the ruthenium-
catalyzed reaction, it was found that base abstracts pro-
ton of the alcohol, which makes the formation of ruthe-
nium alkoxide easier and this alkoxide then undergoes

12 of 19
KILIC ET AL.
TABLE 1
Asymmetric Transfer hydrogenation of acetophenone with iso-PrOH catalyzed by tri-coordinated chiral dioxaborinanes
(T(1–2)B(1–2)) and four-coordinated chiral dioxaborinanes (T(1–2)B(1–2)-N)
Entry
1
Complex
S/C/NaOH
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1
Time
72 hr (144 h)[d]
72 hr (144 h)[d]
72
Conversion(%)[f]
%ee[g]
Configuration[h]
[a]
T1B1
12 (24)[d]
13 (24)[d]
13
12 (8)[d]
13 (8)[d]
S
S
S
S
S
S
S
S
--
--
--
--
--
--
--
--
S
S
S
S
S
S
S
S
S
S
S
S
[a]
2
T2B1
[a]
3
T1B2
10
[a]
4
T2B2
72
14
10
5
T1B1N[a]
T2B1N[a]
T1B2N[a]
T2B2N[a]
72
26
35
6
72
25
34
7
72
22
22
8
72
28
23
[b]
9
T1B1
48 hr (48 hr)[e]
48 hr (48 hr)[e]
48 hr
< 3
< 3
< 3
< 3
< 3
< 3
< 3
< 3
97 (98)[e]
98 (98)[e]
99
--
[b]
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
T2B1
100:1
--
[b]
T1B2
100:1
--
[b]
T2B2
100:1
48 hr
--
T1B1N[b]
T2B1N[b]
T1B2N[b]
T2B2N[b]
100:1
48 hr
--
100:1
48 hr
--
100:1
48 hr
--
100:1
48 hr
--
[c]
T1B1
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1:3
100:1:5
100:1:7
100:1:9
48 hr
16 (14)[e]
16 (14)[e]
[c]
T2B1
48 hr
[c]
T1B2
48 hr
11
[c]
T2B2
48 hr
97
11
T1B1N[c]
T2B1N[c]
T1B2N[c]
T2B2N[c]
T1B1N[d]
T1B1N[d]
T1B1N[d]
T1B1N[d]
24 hr
98
38
24 hr
98
40
24 hr
97
28
24 hr
99
30
24 hr
92
33
24 hr
98
38
24 hr
94
35
24 hr
94
33
Reaction conditions
[a]At room temperature; acetophenone/Cat./NaOH, 100:1:5;
[b]Refluxing in isoPrOH; acetophenone/Cat., 100:1, in the absence of base;
[c]Refluxing in isoPrOH; acetophenone/Cat./NaOH, 100:1:5;
[d]At room temperature; acetophenone/Cat./NaOH, 100:1:5, (64 hr);
[e]Refluxing in isoPrOH; acetophenone/Cat./KOH, 100:1:5;
[f]Determined by GC (three independent catalytic experiments);
[g]Determined by capillary GC analysis using a chiral cyclodex B (Agilent) capillary column;
[h]Determined by comparison of the retention times of the enantiomers on the GC traces with literature values.
enantioselectivity were obtained with a base ratio of
100:1:5 (Entry 25–28). Having established the optimum
reaction conditions, we set out to explore the substrate
generality of the asymmetric transfer hydrogenation of
acetophenone derivatives. The introduction of electron-
withdrawing substituents, such as F, Cl, Br or NO2, on

KILIC ET AL.
13 of 19
TABLE 2
Asymmetric Transfer Hydrogenation results for substituted acetophenones catalyzed by tri-coordinated chiral
dioxaborinanes (T(1–2)B(1–2)) and four-coordinated chiral dioxaborinanes (T(1–2)B(1–2)-N)[a]
Entry
Catalyst
Substrate
Product
Time
16 hr
Conv.(%)[b]
ee(%)[c]
Config.[d]
1
T1B1
98
98
98
96
97
99
98
99
98
97
97
99
98
99
99
98
96
97
98
99
98
99
97
98
98
99
99
99
97
96
98
98
98
99
99
99
97
15
15
12
13
37
38
28
28
14
13
12
11
36
36
25
26
13
12
10
11
36
36
24
26
11
11
10
10
33
33
23
25
16
17
13
12
41
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
2
T2B1
16 hr
16 hr
16 hr
8 hr
3
T1B2
4
T2B2
5
T1B1N
T2B1N
T1B2N
T2B2N
T1B1
6
8 hr
7
8 hr
8
8 hr
9
24 hr
24 hr
24 hr
24 hr
12 hr
12 hr
12 hr
12 hr
30 hr
30 hr
30 hr
30 hr
16 hr
16 hr
16 hr
16 hr
16 hr
16 hr
16 hr
16 hr
8 hr
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
T2B1
T1B2
T2B2
T1B1N
T2B1N
T1B2N
T2B2N
T1B1
T2B1
T1B2
T2B2
T1B1N
T2B1N
T1B2N
T2B2N
T1B1
T2B1
T1B2
T2B2
T1B1N
T2B1N
T1B2N
T2B2N
T1B1
8 hr
8 hr
8 hr
3 days
3 days
3 days
3 days
3/2 days
T2B1
T1B2
T2B2
T1B1N
(Continues)

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KILIC ET AL.
TABLE 2 (Continued)
Entry
38
Catalyst
T2B1N
Substrate
Product
Time
Conv.(%)[b]
ee(%)[c]
Config.[d]
3/2 days
97
43
S
39
40
41
42
43
44
45
46
47
48
T1B2N
T2B2N
T1B1
3/2 days
3/2 days
6 days
6 days
6 days
6 days
3 days
3 days
3 days
3 days
96
98
97
99
97
96
96
99
97
99
30
32
10
10
10
10
32
32
20
23
S
S
S
S
S
S
S
S
S
S
T2B1
T1B2
T2B2
T1B1N
T2B1N
T1B2N
T2B2N
Reaction conditions
[a]Catalyst (0.005 mmol), substrate (0.5 mmol), iso-PrOH (5 ml), NaOH (0.025 mmol %), 82 ꢀC, the concentration of acetophenone derivatives
is 0.1 M;
[b]Purity of compounds is checked by 1H NMR and GC (three independent catalytic experiments), yields are based on aryl ketone;
[c]Determined by capillary GC analysis using a chiral cyclodex B (Agilent) capillary column (30 m x 0.32 mm I.D. x 0.25 μm film thickness);
[d]Determined by comparison of the retention times of the enantiomers on the GC traces with literature values.
the 4-position of the phenyl ring of the acetophenone
derivatives resulted in improved activity, while there was
no significant change in enantioselectivity (Entries 1–32,
Table 2). The introduction of electron-withdrawing sub-
stituents to the para position of the phenyl ring of the
ketone decreased the electron density of the C=O bond
so that the activity was improved giving rise to easier
hydrogenation and undergoes hydrogenation faster than
that of acetophenone.[55,63,64] Furthermore, the influence
of positions of electron-donating groups on transfer
hydrogenation was studied. It appears that the conver-
sions and enantioselectivities are sensitive for the
position of electron-donating substituents on the phenyl
ring. Both conversion and enantioselectivity are higher
for ortho-methoxy substituted acetophenone than those
for para-methoxy substituted one (Entry 33–48).
As seen in Table 3, complex T1B1-N catalyzed the
reduction of aryl/alkyl and alkyl/alkyl ketones to their
corresponding alcohols with >95% conversion. These
ketones took a longer time to react compared to
acetophenone derivatives. Furthermore, a variety of sim-
ple alkyl/alkyl ketones were transformed into the
corresponding secondary alcohols and it was found that
the activity and selectivity were highly dependent on the
steric hindrance of the alkyl group. Namely, when the
size of the alkyl group increased, the activity and selectiv-
ity decreased (Entry 1–4). In addition, as can be seen
from Entry 5, 1-naphthyl methyl ketone was reduced
with the highest conversion and enantioselectivity. When
entries 7 and 8 were considered, the replacement of CH3
with C6H5 in the ketone decreases reaction rate.
3.4 | Biological activities
3.4.1 | DPPH radical scavenging activity
The decrease in the absorbance of the DPPH radical
occurs during the incubation period. This is because
antioxidants take hydrogen from radicals or give
electrons. Due to this feature, DPPH is often used as a
substrate to evaluate the antioxidant activity of organic
and inorganic substances.[65] As shown in Figure 6, all
chiral dioxaborinane complexes showed different rates of
radical scavenging activity. The dioxaborinane T2B2N
exhibited the highest activity among all chiral
dioxaborinane complexes. When the concentration of this
dioxaborinane complex was increased from 25.0 μg/ml to

KILIC ET AL.
15 of 19
TABLE 3
Asymmetric Transfer Hydrogenation results for various ketones catalyzed chiral dioxaborinane T2B1N[a]
Entry
Complex
T2B1N
T2B1N
T2B1N
T2B1N
T2B1N
T2B1N
T2B1N
T2B1N
R1
R2
Time (Days)
Conv.(%)[b]
ee(%)[c]
36
Config.[d]
1
2
3
4
5
6
7
8
CH3
CH3
CH3
CH3
CH3
CH3
CH3
C6H5
CH2CH3
CH2CH2C6H5
CH (CH3)2
CH2CH(CH3)2
1-naphthyl
n-C4H9
2
3
96
98
97
98
98
97
96
98
S
S
S
S
S
S
S
S
32
8
32
6
30
3/2
5
42
27
C6H11
3
22
C6H11
6
25
Reaction conditions:
[a]Catalyst (0.005 mmol), substrate (0.5 mmol), isoPrOH (5 ml), NaOH (0.025 mmol %), 82 ꢀC, the concentration of ketones is 0.1 M;
[b]Purity of compounds is checked by 1H NMR and GC (three independent catalytic experiments), yields are based on aryl ketone;
[c]Determined by capillary GC analysis using a chiral cyclodex B (Agilent) capillary column (30 m x 0.32 mm I.D. x 0.25 μm film thickness);
[d]Determined by comparison of the retention times of the enantiomers on the GC traces with literature values.
FIGURE 6 Free radical scavenging
activities of chiral dioxaborinane compounds
200.0 μg/ml, the scavenging rate increased from
42.8 0.83% to 91.4 1.97%. The order of scavenging
peroxidation.[66] As shown in Figure 7, all chiral
dioxaborinane complexes exhibited different rates of
reducing power activity. It was observed that as the con-
centration of the test compounds increased, the activity
of reducing power also increased. Among the chiral
dioxaborinane complexes, the highest reducing power
activity was observed in T1B2 (0.647 0.011) and T2B2
(0.629 0.013) at the concentration of 200.0 μg/ml, while
the lowest activity in the same concentration was
capacity of the chiral dioxaborinane compounds at
200 μg/ml concentration was determined as
T2B2N>T1B2N>T1B2 >T2B2 >T1 >T2 >T2B1 >T2B1N>
T1B1 > T1B1N. At high concentrations, T2B2N exhibited
activity close to Trolox, which is used as a standard
reference substance.
detected in T1B1N (0.357
(0.292 0.009). The α-tocopherol used as a standard
0.015) and T2B1N
3.4.2 | Reducing power activity
Compounds with reducing power can be used as antioxi-
dants to reduce oxidative intermediates in lipid
showed higher activity than the complexes at all concen-
trations studied.

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KILIC ET AL.
FIGURE 7 Reducing power activities of
chiral dioxaborinane compounds
3.4.3 | Antibacterial activity
shape.[67] Due to the binding of CT-DNA to the com-
pounds, free DNA moves faster on the gel since it is
smaller than the bound DNA.[68] Agarose gel electropho-
resis results of CT-DNA bound complexes are given in
Figure 8. According to the results, it was determined that
T1, T1B1 and T2 having little movement on the gel, had
high DNA binding capacity, while T1B2N, T2B1, and
T2B2N had low DNA binding capacity.
The antibacterial activity of new chiral dioxaborinane
compounds was tested against three Gram+ and three
Gram-bacteria. Among the chiral dioxaborinane com-
pounds, only T1B2 (500 μg/ml) exhibited weak
antibacterial activity against two bacteria, while the other
chiral dioxaborinane compounds did not have any activ-
ity. The chiral dioxaborinane T1B2 formed an inhibition
zone of 9 mm against L. pneumophila and 7 mm against
E. hirae. Streptomycin and Tetracycline showed 15 mm
and 21 mm inhibition zone against L. pneumophila,
while they showed 19 mm and mm 22, respectively,
against E. hirae.
3.4.5 | DNA cleavage activity
When super-helical plasmid pBR322 is run under normal
conditions on DNA gel electrophoresis, a single band is
observed on the gel. However, if super-helix DNA
(form I) is subjected to an external effect, its one or two
chains may break. In a break in a single chain, two bands
appear (Form I and Form II) on the gel. When a break in
two chains occurs, three bands (Form I, Form II and
Form III) appear on the gel. The slowest moving
3.4.4 | DNA binding activity
The movement of molecules in the agarose gel electro-
phoresis method depends on their mass, charge, and
FIGURE 8 DNA binding activity of chiral dioxaborinane compounds. Lane M, DNA Marker; Lane C, Kontrol, CT- DNA; Lane 1, CT-
DNA + 200 μg/ml T1; Lane 2, CT- DNA + 200 μg/ml T1B1; Lane 3, CT- DNA + 200 μg/ml T1B1N; Lane 4, CT- DNA + 200 μg/ml T1B2; Lane
5, CT- DNA + 200 μg/ml T1B2N; Lane 6, CT- DNA + 200 μg/ml T2; Lane 7, CT- DNA + 200 μg/ml T2B1; Lane 8, CT- DNA + 200 μg/ml
T2B1N; Lane 9, CT- DNA + 200 μg/ml T2B2; Lane 10, CT- DNA + 200 μg/ml T2B2N

KILIC ET AL.
17 of 19
FIGURE 9 DNA Cleavage activity of chiral dioxaborinane compounds. Lane C, Control, pBR 322 DNA; Lane 1, pBR
322 DNA + 200 μg/ml T1; Lane 2, pBR 322 DNA + 200 μg/ml T1B1; Lane 3, pBR 322 DNA + 200 μg/ml T1B1N; Lane 4, pBR
322 DNA + 200 μg/ml T1B2; Lane 5, pBR 322 DNA + 200 μg/ml T1B2N; Lane 6, pBR 322 DNA + 200 μg/ml T2; Lane 7, pBR
322 DNA + 200 μg/ml T2B1; Lane 8, pBR 322 DNA + 200 μg/ml T2B1N; Lane 9, pBR 322 DNA + 200 μg/ml T2B2; Lane 10, pBR
322 DNA + 200 μg/ml T2B2N
structure is Form II, while the fastest moving structure is
Form I. Form III is positioned between these two struc-
tures.[69] The electrophoresis results of the 200 mg/ml
concentration of chiral dioxaborinane compounds after
incubation with supercoiled plasmid pBR322 DNA are
given in Figure 9. According to the results, a band
(Form I) was obtained for the control untreated with
compounds (Lane C) and two bands (Form I and II) from
the samples treated with the compounds (Lane 1–10). All
the newly synthesized dioxaborinane compounds were
determined to exhibit one strand cleavage activity of
supercoiled DNA.
effect. It has also been shown that complexes have
different rates of DNA binding activity and can break
super-helix DNA from a single chain.
ACKNOWLEDGEMENT
We acknowledge gratefully the financial support from
Research Fund of Harran University (HUBAP Projects
No: 19023) Sanliurfa, Turkey.
CONFLICT OF INTEREST
The authors declare that they have no conflict of interest.
ORCID
Ahmet Kilic https://orcid.org/0000-0001-9073-4339
Murat Aydemir https://orcid.org/0000-0002-4238-5012
Feyyaz Durap https://orcid.org/0000-0003-0899-1948
4 | CONCLUSION
In this study, we synthesized two new cis-1,2-diol-type
chiral ligands (T1 and T2) and their tri-coordinated chiral
dioxaborinane (T(1–2)B(1–2)) and four-coordinated chiral
dioxaborinane adducts with 4-tert-butyl pyridine
sustained by N ! B dative bonds (T(1–2)B(1–2)-N). Two
chiral ligands and their chiral dioxaborinane complexes
were characterized by the FT-IR, UV–Vis, and NMR (1H,
13C, and 11B) spectroscopy, LC–MS/MS, and elemental
analysis. The chiral dioxaborinane complexes were also
used as catalyst for the asymmetric transfer hydrogena-
tion (ATH) of acetophenone derivatives under suitable
conditions. The catalytic results show that the chiral
dioxaborinane complexes are good catalyst precursors. In
tests to determine the biological activities of newly
synthesized chiral dioxaborinane complexes, it was
determined that almost all the chiral dioxaborinane
complexes have antioxidant activity. The T2B2N
exhibited the highest radical scavenging activity among
the complexes. Except for the weak antibacterial effect
exhibited by T1B2, the complexes had no antibacterial
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How to cite this article: Kilic A, Balci TE,
Arslan N, et al. Synthesis of cis-1,2-diol-type chiral
ligands and their dioxaborinane derivatives:
Application for the asymmetric transfer
hydrogenation of various ketones and biological
evaluation. Appl Organomet Chem. 2020;e5835.
https://doi.org/10.1002/aoc.5835
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