1928
X. Zhang et al. / Tetrahedron 74 (2018) 1926e1932
recrystallization. The 1H NMR results of these complexes suggested
the presence of THF after vacuum treatment at room temperature
for 1 h (see ESI). Similar to our previously reported zirconocene
complexes, complexes 1a remained as dry powder after being kept
in open air for six months, while 2a and 3a showed similar stability
over an one-month period. From the viewpoint of operation, such
excellent air-stable complexes have great advantage over zircono-
cene bis(triflate) and the traditional Lewis-acid catalysts.
dioxazepanes.26 Conventional catalysts for the classical Mannich
reaction of aldehyde, ketone and amine were mainly Lewis
acids,27 Bronsted acids28 and Lewis base catalysts.29 However,
these catalysts had one or more disadvantages such as being air-
or moisture-sensitive, low in catalytic efficiency and being
unrecyclable. We applied 1a$2THF$4H2O as a catalyst in one-pot
Mannich reaction under solvent-free condition at room temper-
ature. Depicted in Table
1 were the catalytic efficiency of
These complexes are confirmed to be binuclear structures,
different from the uninuclear structure of Cp2Zr(OH2)3(O-
SO2C8F17)2$THF (4a$THF) even though their synthetic procedures
were totally identical.20c,d One of the Cp ligands can be readily
removed and substituted by OH to form the binuclear structures
in moist air. The binuclear structures show that the zirconium
atoms have distorted octahedral coordination geometry with
the Cp group being trans to the OH unit, such as in the case
1a$2THF$4H2O and its analog 4a$THF. We could see that the
reactions occurred smoothly in the presence of 1a$2THF$4H2O
(2.5 mol%), with the similar yields to those obtained in the pres-
ence of 4a$THF.20d The aromatic aldehydes bearing electron-
withdrawing groups, including chloro and bromo in the phenyl
plane, exhibited slightly higher activity than the aldehydes with
electron-donating groups (entries 1e5). The aromatic ketone
with a methyl group in para-position showed lower activity
because the electron-donating ability of p-CH3 reduced the acidity
of [CpZr(OH2)3]2(
m m
2-OH)2(CF3SO3)4,21 [{CpZr(OH2)3}2( 2-OH)2]
[C6F5SO3]4,22 and [{RCpZr(OH2)3}2(
m
2-OH)2] [C8F17SO3]4 (R ¼ Me,
of ketone a-H (entries 6e8).
Et).20 The ZreO distances of 3a$2C3H6O$8H2O are exemplified to
be 2.083(5), 2.148(5), 2.169(4), 2.175(4) and 2.224(5) Å and the
O(7)-Zr(1)-Zr(#1) angle is 34.75(11)o. The ZreZr distances for 1a,
2a and 3a are 3.5107(5), 3.489(2) and 3.5340(14) Å respectively,
demonstrating that there are no ZreZr interactions. The C8F17SO3ꢁ
ions, the dissociated H2O molecules and the solvating ligand THF
(or acetone) are packed around the complex cations in such a way
their oxygen atoms point toward the H2O ligands. The C8F17 chains
of the anion, on the other hand, are clustered together to produce
hydrophobic domains in the crystal structure.
Alkylation is one of the most common protocols to construct
CeC bonds.30 Recently, different catalysts such as NPW/SiO2,31
PMA/SiO2,32 Phosphotungstic acid (PWA),33 trimethylsilyl
trifluoromethane-sulfonate (TMSOTf),34 Yb(OTf)3,35 B(C6F5)3,36
InCl3,37 FeCl3,38 Fe(ClO4)3,39 bipy-ruthenium complexes,40 TfOH-
43
SiO2,41 Bi(OTf)3,42 and NaHSO4/SiO2 were used in the direct
alkylation of active methylenes with alcohols. These catalytic re-
actions have the advantages of low catalyst loadings, wide avail-
ability of the starting materials and the generation of H2O as the
only side product. But some of the catalysts cannot be recycled and
strictly anhydrous conditions are required in most cases.
The thermal behavior of complexes 1a$2THF$4H2O, 2a$6H2O
and 3a$2C3H6O$8H2O were investigated by thermo-gravimetric-
differential scanning calorimetry (TG-DSC) in N2 atmosphere (see
Fig. S1 in ESI). The TG-DSC curves indicated three stages of weight
loss. The endothermic step below 100 ꢀC can be attributed to the
removal of water and THF (or acetone) molecules. 1a$2THF$4H2O is
stable up to about 300 ꢀC, while 2a$6H2O and 3a$2C3H6O$8H2O are
stable up to 215 and 255 ꢀC, respectively. After that, one weight loss
of exothermic nature emerged, possibly resulting from the oxida-
tion of organic entities. The removal of perfluorooctanesulfuryl li-
gands for the three complexes occurred at about 380 ꢀC, thus
leaving behind the zirconium fluoride compounds.
We assessed the air-stable complex 2a$6H2O (2.5 mol%) as a
Lewis acid catalyst for the direct alkylation of 1,3-dicarbonyl de-
rivatives with alcohols in CH2Cl2 (Table 2). First, the compatibility
of substrates with regard to the benzhydrol derivatives was tested.
Generally, the electron-withdrawing group on the phenyl ring of
benzhydrylic alcohols benefited the yields slightly (Table 2,
entries 1e8). Good yields (87e95%) of targeted products were
also obtained when acetylacetone, benzoylacetone, ethyl
benzoylacetate and ethyl acetoacetate were employed as 1,3-
dicarbonyl derivatives (Table 2, entries 9e12). Notbaly, when 5,
5-dimethylcyclohexane-1,3-dione reacted with benzhydrol, the
desired compound 6m was isolated in moderate yield (Table 2,
entry 13).
Conductivity measurement was applied to investigate their
ionic dissociation behavior in CH3CN (1.0 mmol Lꢁ1) (Table S1, see
ESI). The molar conductivity (L) of 1a$2THF$4H2O, 2a$6H2O and
3a$2C3H6O$8H2O thus measured at 25 ꢀC is 156, 217, 202 S cmꢁ1
m ,
Table 1
respectively. The molar conductivity of 1a$2THF$4H2O is higher
than that of uninuclear Cp2Zr(OH2)3(OSO2C8F17)2$THF
Mannich reactions of aldehyde with amine and acetophenone catalyzed by
1a$2THF$4H2O and 4a$THFa,b
.
(4a$THF).20c,d The large molar conductivity value is consistent
with the complete ionization into a 1:4 electrolyte in CH3CN,
implying that the complexes are cationic in the solid as well as in
the solution state. Compared to the case of 1a$2THF$4H2O and
4a$THF, the existence of bulky n-butyl and t-butyl groups does not
necessarily increase the solubility of 2a$6H2O and
3a$2C3H6O$8H2O in polar organic solvents such as acetone,
CH3CN, THF, EtOAc and MeOH (Table S2, see ESI). Notably, they
have a relatively strong acidity, showing strength of 0.8 < H0 < 3.3
(H0 being the Hammett acidity function, see ESI), the same as
those of zirconocene bis(perfluorooctanesulfonate)s.20c,d In light
of such features of the complexes, we evaluated their perfor-
mances as Lewis acids in Mannich reaction, the benzylation of 1,3-
dicarbonyl derivatives with alcohols, the Michael addition of in-
doles with enone, the three-component aza-Friedel-Crafts reac-
tion and the Friedel-Crafts acylation reaction.
Entry
R1
R2
Product
Yield %
Yield %
1a
4a
1
2
3
4
5
6
7
8
H
H
H
H
H
4-CH3
4-Cl
3-Cl
2-Br
4-CH3
2-Br
2,6-diCl
5a
5b
5c
5d
5e
5f
98
95
99
97
95
93
95
94
97
95
99
96
95
92
95
96
H
CH3
CH3
CH3
5g
5h
a
The mixture of ArCHO (1.0 mmol), PhNH2 (1.0 mmol), ArCOCH3 (1.0 mmol),
catalyst 1a$2THF$4H2O (0.025 mmol) or 4a$THF (0.05 mmol) was stirred at room
temperature for about 10 min.
The Mannich reaction was an effective method for the con-
struction of CeC and CeN bonds.23 The reaction was often used to
prepare emodin derivatives,24 aminonaphthoquinones,25 and
b
Isolated yields.
Zhang, Xiaohong
