Synthesis of air-stable mixed bis-carboxylate titanocene complexes and their catalytic behaviors in cross-aldol and Mannich reactions

Article abstract of DOI:10.1007/s11243-016-0054-3

Tunable organometallic Lewis acid catalysts were developed by combining salicylic acid (H₂-Sal) with benzoic acid (H-Ben), 4-fluorobenzoic acid (H-BenF) and 3-thiophenic acid (H-Th), as coligands for mixed bis-carboxylate titanocene complexes. Three air-stable complexes [Cp₂Ti(η¹-HSal)(η¹-Ben)] (1), [Cp₂Ti(η¹-HSal)(η¹-BenF)] (2) and [Cp₂Ti[η¹-HSal][(η¹-Th)] (3) were prepared in high yields by the reaction of salicylato titanocene chelate with carboxylate ligands. The mixed bis-carboxylate titanocene complexes were fully characterized by physicochemical and spectroscopic methods. Single-crystal X-ray diffraction studies revealed Ti–O_(H-Sal) bond distances in 1, 2 and 3 of 1.972(3), 1.9245(18) and 1.912(5)??, respectively, while the bond distances involving the coligands of 1, 2 and 3 are 1.908(3)?? (Ti–O_Ben), 1.9296(19)?? (Ti–O_BenF) and 1.945(5)?? (Ti–O_Th), respectively. These bis-carboxylate titanocene complexes showed satisfactory activities and selectivities in Mannich and cross-aldol reactions. Notably, complex 3 bearing the labile thiophene carboxylate ligand gave high yields with a diastereomer ratio (d.r.) as high as 1:99 for the direct Mannich reactions of benzaldehyde, cyclohexanone and aniline. In cross-aldol reaction of benzaldehyde and cyclohexanone, 1 and 2 successfully catalyzed the formation of double-aldol products in up to 99?% yield.

Full text of DOI:10.1007/s11243-016-0054-3

Transit Met Chem (2016) 41:731–738
DOI 10.1007/s11243-016-0054-3
Synthesis of air-stable mixed bis-carboxylate titanocene complexes
and their catalytic behaviors in cross-aldol and Mannich reactions
1
1
1
1
1
•
Jing Wang
Guo-Fang Zhang
•
Xi Chen
1
•
Xiu Wang
1
•
Wei-Qiang Zhang
1
•
Hua-Ming Sun
•
Ya Wu
•
Zi-Wei Gao
Received: 15 February 2016 / Accepted: 22 April 2016 / Published online: 4 August 2016
Ó Springer International Publishing Switzerland 2016
Abstract Tunable organometallic Lewis acid catalysts were
developed by combining salicylic acid (H -Sal) with benzoic
catalyzed the formation of double-aldol products in up to
99 % yield.
2
acid (H-Ben), 4-fluorobenzoic acid (H-BenF) and 3-thio-
phenic acid (H-Th), as coligands for mixed bis-carboxylate
titanocene complexes. Three air-stable complexes [Cp
2
-
1
1
1
1
Ti(g -HSal)(g -Ben)] (1), [Cp Ti(g -HSal)(g -BenF)] (2)
Introduction
2
1
1
and [Cp Ti[g -HSal][(g -Th)] (3) were prepared in high
2
yields by the reaction of salicylato titanocene chelate with
carboxylate ligands. The mixed bis-carboxylate titanocene
complexes were fully characterized by physicochemical and
spectroscopic methods. Single-crystal X-ray diffraction
studies revealed Ti–O(H-Sal) bond distances in 1, 2 and 3 of
Organometallic Lewis acids have been of widespread
interest in coordination chemistry and homogenous catalysis
due to their activity in classic organic transformations [1–5].
Hard donor ligands are vital to improve the acidity of a wide
spectrum of organometallic Lewis acids [6]. Some heteroa-
tom ligands were introduced into organometallic Pd, Ru and
Ir complexes, resulting in effective catalysts capable of
performing Friedel–Crafts, aldol and Michael reactions with
high selectivity [7]. Some weakly coordinating anions, in
accordance with hard and soft acid–base theory, have been
used for the development of air-stable Lewis acid cataylsts.
For instance, cationic titanocene perfluoroalkyl(aryl)sul-
˚
1
.972(3), 1.9245(18) and 1.912(5) A, respectively, while the
bond distances involving the coligands of 1, 2 and 3 are
˚
.908(3) A (Ti–OBen), 1.9296(19) A (Ti–OBenF
˚
1
)
and
˚
.945(5) A (Ti–O ), respectively. These bis-carboxylate
1
Th
titanocene complexes showed satisfactory activities and
selectivities in Mannich and cross-aldol reactions. Notably,
complex 3 bearing the labile thiophene carboxylate ligand
gave high yields with a diastereomer ratio (d.r.) as high as
fonate complexes [8], [Zr(Cp)
][O
][OSO
[10] and the organobismuth complex [S(CH C H )
2 6 4 2-
O
C
F
]
Á3H
OÁTHF
2
S
2
8
17
2
2
2
1
:99 for the direct Mannich reactions of benzaldehyde,
[9], [{CpHf(OH
2
)
3
}
2
(l -OH)
2
2
C
4
F
9
]
4
Á4H OÁ2THF
2
cyclohexanone and aniline. In cross-aldol reaction of ben-
?
-
zaldehyde and cyclohexanone, 1 and 2 successfully
Bi(OH )] [ClO ] [11], showed high efficiency in ligand-
2 4
accelerated carboxyl group transformation reactions.
Recently, Rauchfuss reported protonation enhanced Lewis
acidity of iridium complexes containing noninnocent ami-
dophenolates [12]. This enlightened us that introducing
Brønsted acid ligands into the coordination sphere of
organometallic complexes is a potential strategy to tune the
corresponding Lewis acidity and hence the catalytic activity
[13–15].
Electronic supplementary material The online version of this
article (doi:10.1007/s11243-016-0054-3) contains supplementary
material, which is available to authorized users.
&
&
Ya Wu
wuya@snnu.edu.cn
Zi-Wei Gao
zwgao@snnu.edu.cn
Group IV metallocenes are attractive building blocks for
organometallic Lewis acid catalysts due to the electroni-
cally tunable metal center and intrinsic Lewis acidity
[16–18]. Our previous research found that titanocene
1
Key Laboratory of Applied Surface and Colloid Chemistry,
MOE/School of Chemistry and Chemical Engineering,
Shaanxi Normal University, Xi’an 710119, China
123

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Transit Met Chem (2016) 41:731–738
containing two identical salicylato ligands showed great
activity in the direct three-component Mannich reaction of
benzaldehyde, aniline and acetophenone [19]. As for
might be protonated and generate a vacant site [23]. This
provides a strong theoretical basis for the synthesis of mixed
bis-carboxylate titanocene complexes. In addition, the syn-
thesis of the salicylato titanocene chelate 4 is mature and can
be carried out on a large scale (Scheme 1a) [24]. Therefore,
we surmised that direct reaction of the salicylato titanocene
chelate (4) with the required carboxylic acids might furnish
the mixed bis-carboxylate titanocene complexes. This pro-
cedure was successfully applied for the preparation of
3
-pentanone, although bis-salicylato titanocene gave high
activity, this catalyst was unfavorable for high diastereos-
electivity of the Mannich reaction. We anticipated that
replacing one of the salicylato ligands by a weak acid
ligand might fine-tune the activity of titanocene complexes
and therefore increase the selectivity for condensation
reactions of organic ketones. Herein, we report an atom-
economic preparation of titanocene complexes containing
two distinct types of ligand, affording Lewis acid catalysts.
Three such mixed bis-carboxylate titanocene complexes
were prepared and fully characterized. In contrast to the
well-known metallocene triflates [20, 21], these complexes
were stable in open air over 3 months, which can be
attributed to the presence of rich hydrogen bonds in the
molecular structures of the complexes. Their catalytic
behaviors were assessed for Mannich and cross-aldol
reactions.
1
1
1
1
[Cp Ti(g -HSal)(g -Ben)]
(1),
[Cp Ti(g -HSal)(g -
2
2
1
1
BenF)] (2) and [Cp Ti[g -HSal][(g -Th)] (3) in high yields
2
(ca. 90 %) (Scheme 1b–d).
The FTIR spectra of the complexes are shown in fig-
ures S4–S6 (Supporting Information). The O–H stretching
-
1
bands are observed at 3446, 3489 and 3614 cm for 1, 2 and
3, respectively. The differences probably arise from internal
hydrogen bonds, O–HÁÁÁO and O–HÁÁÁF. Characteristic
-
1
absorptions at 3089, 3097 and 3103 cm are assigned to
C–H stretching vibrations of the cyclopentadienyl (Cp) and
benzene rings. The benzene skeleton vibrations exhibit
-
1
absorption bands around 1448–1488 cm . In addition,
given the different carboxylate ligands, strong absorption
-
bands at 1571 and 1637 cm for complex 1, 1597 and
1
Results and discussion
-
637 cm for complex 2, and 1574 and 1628 cm for
1
-1
1
Synthesis and characterization
complex 3 can be assigned to asymmetrical carboxylate
vibrations. The Ar–O stretching frequency is observed at
–
1
The stepwise substitution of the chloride ligands in titano-
cene dichloride by different carboxylate ligands is uncon-
trollable, since the incoming oxygen donor ligands have
similar coordination abilities and can coordinate with Ti
simultaneously [22]. Marc reported 13 distinct coordination
1301, 1302 and 1296 cm for 1, 2 and 3, respectively. The
data support the formation of titanocene complexes con-
taining two distinct carboxylate ligands.
Thermal behaviors of all three complexes were exam-
ined by TG methods (Figure S10, Supporting Information).
No obvious weight loss is found for any of the complexes
before 125 °C. The TG analysis for 1 shows an initial
modes of the salicylato ligand with Ti, suggesting that the
2
salicylato ligand of the titanocene chelate Cp Ti(g -Sal) (4)
2
Scheme 1 Preparation of
titanocene complexes with
aromatic carboxylate ligands
HO
O
1 epuiv
(
b)
1
COOH
O
O
Ti
Ti
Yield 90%
CHCl , rt, 30min
3
O
HO
O
1
epuiv
COOH
c) 1 epuiv
F COOH
(
O
2
(
a)
Cl
Cl
O
O
O
O
OH
CHCl / H O
rt, 30min
Ti
Ti
Yield 92%
CHCl
, rt, 30min
3
2
3
F
O
4
HO
O
1
epuiv
COOH
3
(d)
O
O
S
Yield 88%
Ti
CHCl , rt, 30min
3
S
O
1
23

Transit Met Chem (2016) 41:731–738
733
weight loss of 16.8 % in the temperature range of
and 3, respectively, which are in good agreement with the
5
1
25–220 °C, which can be assigned to the loss of CO , CO
corresponding distances in other (g -C H ) Ti complexes
2
5 5 2
and an H atom. The next loss of 29.9 % in the temperature
[25–29] (Cp1 centroid represents the center of the plane
formed by C1–C5, and Cp2 centroid represents the center
of the plane formed by C6–C10). The O–Ti1–O angles for
1, 2 and 3 are 91.7(2)°, 90.6(2)° and 91.0(3)°, respectively,
similar to those observed in other titanocene complexes
range of 250–520 °C corresponds to the removal of two Cp
rings. The final residue is assigned to TiO plus carbon. For
2
complexes 2 and 3, similar mass loss processes were
observed, showing that these complexes have similar
thermal stabilities.
5
such as (g -C H ) Ti(O CC H -2-OH) [90.1(1)°] [30],
5
5 2
2
6
5
2
5
(
g -C H ) Ti(O CC H )
[91.4(3)°]
[17]
and
5
5 2
2
6 5 2
Crystal structures
Crystals of complexes 1–3 were obtained by diffusion of
hexane into saturated solutions of the complexes in CH2-
Cl . The crystal and refinement data are listed in Table 4,
2
and their molecular structures are shown in Figs. 1, 2 and 3
with selected bond lengths and angles in Tables S1–S3
(
Supporting Information). All three complexes crystallize
in the monoclinic space group P2(1)/c; each molecule
consists of two cyclopentadienyl groups, one Ti metal ion,
one salicylate and one carboxylate (benzoate for 1, 4-flu-
orobenzoate for 2 and 3-thiophene carboxylate for 3). In
˚
complex 1, the bond length of Ti–O1(H-Sal) is 1.972(3) A,
˚
while Ti1–O4(Ben) is shorter, at 1.908(3) A. For complex 2,
which has a para-fluorine substituent in the benzoic acid
˚
ligand, the bond length of Ti–O1(H-Sal) is 1.9245(18) A,
˚
whereas Ti1–O4(BenF) is 1.9296(19) A, which is longer
than in complex 1. The bond lengths of Ti–O1(H-Sal) and
Ti1–O4(BenF) in complex 2 are quite close. For complex 3,
˚
the bond length of Ti1–O1(H-Sal) is 1.912(5) A, while Ti1–
Fig. 2 ORTEP diagram of complex 2 with thermal ellipsoids drawn
at a 50 % probability limit
˚
O4(Th) is 1.945(5) A, longer than Ti–OH-Sal. These differ-
ences provide the possibility of high efficiency and selec-
tivity in catalytic processes. The Ti–C distances for 1–3
˚
cover a narrow range from 2.320(3) to 2.382(7) A. The
distances from the central Ti to the Cp1 centroid are
˚
2
.0376(2), 2.0423(5) and 2.0512(7) A and to the Cp2
˚
centroid are 2.0556(5), 2.0514(2) and 2.0486(3) A for 1, 2
Fig. 1 ORTEP diagram of complex 1 with thermal ellipsoids drawn
at a 50 % probability limit
Fig. 3 ORTEP diagram of complex 3 with thermal ellipsoids drawn
at a 50 % probability limit
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Transit Met Chem (2016) 41:731–738
Cp Ti(OCOCF ) [90.14(7)°] [27]. The Cp1 centroid–Ti–
Lewis acid catalysts [36–38]. However, poor diastereose-
lectivity and aldol side products were still observed, plus
longer reaction times were needed. Due to the fact that the
Mannich reaction only needs a weak Lewis acid catalyst,
we have performed Mannich reactions using the present
mixed bis-carboxylate titanocene complexes as catalysts
(Table 1). Initially, we optimized the experimental condi-
tions including the catalyst loading, substrate ratio and
temperatures (Table S4, Supporting Information). The best
results were obtained when employing 5 mol% catalyst,
1.0 equivalent of benzaldehyde, 1.5 equivalents of aniline
and 2.0 equivalents of cyclohexanone at room temperature.
High efficiency and diastereoselectivity were obtained
under the optimized conditions. It is worth noting that
complex 3 with a more appropriate Lewis acidity per-
formed better than complexes 1 and 2 in these
experiments.
2
3 2
Cp2 centroid angles for 1, 2 and 3 are 132.750(2)°,
31.844(3)° and 132.210(2)°, respectively, consistent with
1
the reported values of 131.5(3)°–133.6(2)° in other com-
plexes with similar structures [25–27, 30–33].
The two phenyl rings in the salicylic acid and the ben-
zoic acid/4-fluorobenzoic acid ligands are clearly nonpla-
nar in complexes 1 and 2. The dihedral angle between the
two phenyl rings is 20.813(2)° in complex 1 and 47.807(3)°
in complex 2, the latter being much larger than the former.
For complex 3, the dihedral angle between the phenyl and
thiophene rings is closer to that in 2 (40.153(2)°). The two
Cp rings are also nonplanar and the dihedral angles
between them are 50.169(3)°, 50.347(5)° and 50.585(2)°
for 1–3, respectively, indicating that the introduction of the
hetero-ligands has little effect on the two Cp rings. Finally,
the metallocenes are interconnected through intermolecular
hydrogen bonds (Table S4, Supporting Information) to
produce an infinite three-dimensional supramolecular net-
work (Figures S1–S3, Supporting Information).
In order to further investigate the catalytic efficiency of
these mixed bis-carboxylate titanocene complexes, we
chose the best-performing complex 3 as a catalyst for the
Mannich reactions of substituted aromatic aldehydes and
anilines under the optimized conditions. Aromatic alde-
hydes with both electron-donating and electron-withdraw-
ing groups were employed (Table 2, entries 2–5). High
yields and good diastereomer ratio (d.r.) were obtained.
Electron-withdrawing substituents on the aniline exhibit
higher activities, due to enhanced electrophilic ability of
the intermediate imine, whereas electron-donating groups
showed the opposite effect.
Catalytic behaviors in Mannich and cross-aldol
reactions
The Mannich reaction is one of the most useful carbonyl
transformation reactions and is crucial in the synthesis of a
range of valuable pharmaceuticals [34]. Proper control of
the Mannich reaction is challenging because side reactions
such as the aldol reaction can lower the yield [35].
Impressive achievements have been made in the use of the
Mannich reaction for stereoselective synthesis with various
The cross-aldol reaction catalyzed by a Lewis acid
0
provides an effective synthesis of a,a -bis (substituted
Table 1 Mannich reactions of benzaldehyde, aniline and cyclohexanone catalyzed by titanocene catalysts
O
O
HN
O
HN
CHO
NH2
catalyst (5 mol%)
+
+
+
solvent-free,
RT, 2h
a
b
Entry
Catalyst
Yield (%)
Diastereomer ratio
1
2
3
4
5
6
7
Complex 1
Complex 2
Complex 3
Complex 4
Complex 5
Complex 6
81
83
91
66
62
68
17
9:91
8:92
7:93
15:85
32:68
12:88
49:51
c
d
2 2
Cp TiCl
Reaction conditions: 1.0 mmol of Aldehyde, 1.5 mmol of amine, 2 mmol of cyclohexanone, solvent-free, catalyst, 0.05 mmol, 25 °C
a
Isolated yield are obtained after purification by column chromatography
1
Determined by H NMR
b
c
d
Complex 5 is bis-benzoate titanocene complex
Complex 6 is bis-salicylate titanocene complex
1
23

Transit Met Chem (2016) 41:731–738
735
Table 2 Mannich reactions of substituted aldehydes, amines and cyclohexanone catalyzed by complex 3
a
b
d.r.
Entry
R
1
R
2
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
H
H
2
3
3
2
2
3
3
3
91
81
94
88
98
81
87
89
7:93
\1:99
3:97
o-Cl
o-Br
o-OCH
p-Cl
H
H
H
3
H
1:99
p-Cl
m-CH
o-Cl
\1:99
3:97
3
H
\1:99
12:88
H
p-NO
2
Reaction conditions: 1.0 mmol of aldehyde, 1.5 mmol of amine and 2 mmol of cyclohexanone, solvent-free, catalyst 3, 0.05 mmol, 25 °C
a
Isolated yields are obtained after purification by column chromatography
1
Determined by H NMR
b
benzylidene)cycloalkanones, which are intermediates for
synthesis of bioactive pyrimidine derivatives [39]. Differ-
ent types of condensation products can be produced in
aldol reactions [40–42], including monoaldol and double-
aldol products. Therefore, chemoselectivity is the key to
the reaction. To the best of our knowledge, efficient Lewis
acid catalysts based on mixed bis-carboxylate titanocene
complexes have been scarcely reported. A large set of
experiments demonstrated the activity of these titanocene
complexes as catalysts in the cross-aldol reaction (Fig-
ure S12, Supporting Information). The reactions employed
99 %. The reaction outcome was not significantly affected
by the presence of substituents with different electronic
properties. Furthermore, sterically hindered aldehydes still
furnished the desired products in good yields.
Conclusions
In this article, we developed the facile synthesis of mixed bis-
carboxylate titanocene complexes. The crystal structures
established that the Ti centers in these complexes are coordi-
nated by different carboxylate ligands, enhancing their cat-
alytic activities. In catalytic experiments, the complexes
showed satisfactory activities for two important C–C bond
forming reactions. This work should allow for future devel-
opment of more tunable organometallic Lewis acid catalysts.
Studies on the synthesis of a range of other mixed bis-car-
boxylate titanocene complexes and their catalytic activities for
C–C bond formation reactions are ongoing in our laboratory.
5
mol% of catalyst, 1.0 equivalent of aldehyde and 2.0
equivalents of cyclohexanone at 80 °C. Complex 1 sig-
nificantly accelerated the reaction, with yields up to 95 %
under the optimized conditions. Control experiments using
the readily available bis-salicylato titanocene complex, bis-
benzoate titanocene complex and salicylato titanocene
chelate afforded the product in only 72, 69 and 67 %
yields, respectively. Complex 2 with an electron-with-
drawing fluorine on the benzoic acid ring showed no sig-
nificant catalytic activity, while with complex 3, the yield
was decreased slightly. A comparative experiment using
Cp TiCl as catalyst just gave 43 % yield, demonstrating
Experimental
2
2
that the introduction of hetero-ligands has dramatically
improved the Lewis acidity of Cp TiCl , and is crucial for
Materials and methods
2
2
the activities and chemoselectivities of these Lewis acid
catalysts.
All the chemicals and reagents were of analytical grade and
were used without further purification. Salicylato titanocene
chelate was prepared by a previously reported procedure
(Supporting Information) [24]. These complexes, b-amino
ketones and a,b-unsaturated carbonyl compounds, were
The scope and limitations of the new catalysts system
were evaluated with aromatic aldehydes involving elec-
tron-donating and electron-withdrawing substituents
1
13
(Table 3). We chose complexes 1 and 2 for these experi-
ments. The product yields from these reactions were up to
characterized by FTIR, H NMR and C NMR; d.r. of b-
amino ketones was determined by H NMR. FTIR spectra
1
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Transit Met Chem (2016) 41:731–738
Table 3 Aldol reactions of various aldehydes catalyzed by complexes 1 and 2
a
Entry
R
Time (h)
Yield (%)
1
2
1
2
3
4
5
6
7
8
9
H
2.5
3
95
91
97
98
96
98
97
91
99
90
85
86
95
96
96
93
97
97
96
97
98
94
99
95
88
90
96
96
o-OCH
3
m-OCH
3
3
p-OCH
o-Cl
p-Cl
p-F
3
1.5
3
3
3
o-Br
m-Br
p-Br
3
3
10
11
12
13
14
1
o-NO
m-NO
p-NO
p-CH
2
3
2
2
2
3
3
1.5
Reaction conditions: 1.0 mmol of aldehyde, 2 mmol of cyclohexanone, catalyst 1/2, 0.05 mmol, 80 °C, solvent-free
a
Isolated yield are obtained after purification by column chromatography
–
1132(m), 1022(w), 760(m), 707(m) cm . H NMR
1
1
were recorded on a Bruker tensor 27 spectrometer in KBr
-
with absorptions given in cm . H NMR and C NMR
1
1
13
(400 MHz, CDCl ): d 11.98 (s, 1H, OH), d 6.65 (s, 10 H,
3
spectra were obtained on a Bruker Avance 400 MHz spec-
1
trometer in CDCl solution with tetramethylsilane ( H) as
Cp-H). Anal. Calc. (%) for C H O Ti: C, 66.1; H, 4.6.
4 20 5
2
Found (%): C, 66.0; H, 4.5.
3
internal standard. Chemical shifts are given in ppm and
referenced internally to the residual solvent signal. J values
are in Hz. Elemental analyses were obtained with a Vario EL
III Elemental Analyzer, Germany. Single-crystal X-ray
diffraction measurements were taken with a Bruker SMART
APEX-II CCD detector using graphite monochromated
1
1
Synthesis of [Cp Ti(g -HSal)(g -BenF)] (2)
2
Salicylato titanocene chelate (1 mmol, 0.314 g) and 4-flu-
orobenzoic acid (1 mmol, 0.1401 g) were mixed with
CHCl (40 mL). The mixture was heated to 25 °C and
3
˚
MoKa radiation (k = 0.71073 A). Structures were solved
by applying the direct method using SHELXS-97 [43]. The
stirred for 30 min. The solvent was then removed by rotary
evaporation, and the crude product recrystallized from
CH Cl /hexane. The yield of complex 2 was up to 92 %.
crystallographic data are listed in Table 4. The full-matrix
2
least-squares refinement on F included atomic coordinates
2
2
Orange powder. M.p. 118.4–119 °C. IR (KBr): 3489(m),
3097(m), 1637(s), 1597(s), 1488(m), 1448(m), 1302(s),
–
1242(s), 1084(m), 1018(w), 825(m), 760(m) cm .
and anisotropic thermal parameters for all non-H atoms. H
atoms were included using a riding model.
1
1
H
NMR (400 MHz, CDCl ): d 11.94 (s, 1H, OH), d 6.65 (s,
3
1
1
Synthesis of [Cp Ti(g -HSal)(g -Ben)] (1)
10 H, Cp-H). Anal. Calc. (%) for C H FO Ti: C, 63.4; H,
24 19
2
5
4.2. Found (%): C, 63.3; H, 4.2.
Salicylato titanocene chelate (1 mmol, 0.314 g) and ben-
zoic acid (1 mmol, 0.1221 g) were mixed with CHCl3
1
1
Synthesis of [Cp Ti(g -HSal)(g -Th)] (3)
2
(
40 mL). The mixture was heated to 25 °C and stirred for
0 min. The solvent was then removed on a rotary evap-
orator, and the crude product recrystallized from CH Cl /
3
A mixture of salicylato titanocene chelate (1 mmol,
0.314 g) and 3-thiophenecarboxylic acid (1 mmol,
2
2
hexane. The yield of complex 1 was up to 90 %. Orange
powder. M.p. 122.3–123 °C. IR (KBr): 3446(m), 3089(m),
0.1282 g) in CHCl (40 mL) was heated to 25 °C and
3
stirred for 30 min. The solvent was removed by rotary
1
637(s), 1571(s), 1483(m), 1448(m), 1301(s), 1244(s),
evaporation, and the residue was recrystallized from
1
23

Transit Met Chem (2016) 41:731–738
737
Table 4 Crystallographic data and structure refinement data for 1–3
Compounds
1
2
3
Empirical formula
Formula wt.
C
24
H
20
O
5
Ti
C
24
H
19FO
5
Ti
C
22 18 5
H O STi
436.30
296(2)
454.29
296(2)
442.32
296(2)
Temperature/K
Crystal system
Space group
Monoclinic
P2(1)/c
12.6326(8)
7.6097(5)
21.7417(12)
90.00
Monoclinic
P2(1)/c
Monoclinic
P2(1)/c
˚
a/A
10.1875(5)
13.1319(6)
16.1397(8)
90.00
10.4195(4)
12.8994(5)
15.5948(6)
90.00
˚
b/A
˚
c/A
a/°
b/°
c/°
96.290(5)
90.00
107.375(6)
90.00
107.733(4)
90.00°
1996.43(13)
4
3
˚
Volume (A )
2077.5(2)
4
2060.67(17)
4
Z
3
q
calcd (g/cm )
1.395
1.464
1.472
-
1
)
l(MoKa) (mm
F(000)
0.445
0.458
0.565
904
936
912
h range (°)
Index ranges
3.13–26.00
3.07–25.99
3.16–26.00
-15 B h B 15, -9 B k
B 7, -26 B l B 26
-12 B h B 12, -16 B k
B 16, -19 B l B 19
-12 B h B 12, -15 B k
B 15, -19 B l B 19
Reflections collected
13,301
20,853
20,110
Independent reflections (Rint.)
Data/restraints/parameters
4081 (Rint = 0.0348)
4081/3/280
1.110
4032 (Rint = 0.0348)
4032/0/298
1.014
3865 (Rint = 0.0316)
3865/37/262
0.998
2
Goodness of fit on F
Final R indices [I [ 2r(I)]
R indices (all data)
R
R
1
1
= 0.0672, wR
2
2
= 0.1672
= 0.1848
R
R
1
1
= 0.0430, wR
2
2
= 0.0989
= 0.1117
R
R
1
1
= 0.0996, wR
= 0.1253, wR
2
2
= 0.2056
= 0.2211
= 0.0967, wR
= 0.0697, wR
-
3
)
˚
Largest diff. peak/hole (e A
0.328/-0.325
0.211/-0.177
1.638/-0.848
CH Cl /hexane. The yield of complex 3 was up to 88 %.
2
General procedure for cross-aldol reaction
2
Orange powder. M.p. 110.7–111.6 °C. IR (KBr): 3614(m),
3
103(m), 1628(s), 1574(s), 1520(w), 1481(w), 1450(m),
–1 1
392(s), 1296(s), 1248(s), 1020(w), 825(s), 754(s) cm . H
An oven-dried Schlenk tube was charged with complexes 1
or 2 (5 mol%), aldehyde (1 mmol) and cyclohexanone
(2 mmol). The mixture was stirred at 80 °C for 1 h, while
being monitored by TLC until the conversion of aldehyde
to product reached its maximum. The crude product was
extracted with ethyl acetate and further purified by column
chromatography on silica gel using ethyl acetate/hexane as
the eluent. A series of products were obtained from dif-
ferent aromatic aldehydes (Table 3). All products were
1
NMR (400 MHz, CDCl ): d 11.91 (s, 1H, OH), d 6.65 (s,
3
1
0 H, Cp-H). Anal. Calc. (%) for C H O STi: C, 59.7; H,
22 18 5
4
.1. Found (%): C, 59.8; H, 4.1.
General procedure for Mannich reaction
1
13
A mixture of aldehyde (1.0 mmol), amine (1.1 mmol),
ketone (1.5 mmol) and catalyst 3 (5 mmol%) was stirred in
a Schlenk tube at 25 °C for 2 h and monitored by TLC
until the conversion of aldehyde to product reached its
maximum. The crude product was extracted with ethyl
acetate and purified by column chromatography on silica
gel using ethyl acetate/hexane as the eluent. The reaction
was optimized and carried out with a series of aromatic
aldehydes and amines (Table 2). All products were
authenticated by means of their H and C NMR spectra
(Supporting Information).
Supplementary data
CCDC 1029085 (1), 1063552 (2) and 1402226 (3) contain
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_request/cif.
1
13
authenticated by means of their H and C NMR spectra
Supporting Information).
(
123

7
38
Transit Met Chem (2016) 41:731–738
Acknowledgments This work was supported by the 111 Project
B14041), the grant from National Natural Science Foundation of
20. Hollis TK, Robinson NP, Bosnich B (1992) J Am Chem Soc
114:5464–5466
(
China (21271124, 21272186 and 21371112), the Fundamental Funds
Research the Central Universities (GK201501005, GK201302015),
the Fundamental Research Funds for the Central Universities (No.
GK201302015), Natural Science Basic Research Plan in Shaanxi
Province of China (Program No. 2015JQ2056) and Innovation Funds
of Graduate Programs, SNNU (2015CXS039).
21. Hollis TK, Robinson NP, Bosnich B (1992) Organometallics
11:2745–2748
22. Gao ZW, Zhang CY, Dong MY, Gao LX, Zhang GF (2006) Appl
Organometal Chem 20:117–124
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5. D o¨ ppert K, Sanchez-Delgado R, Klein H, Thewalt U (1982) J
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