Thioacetalization of aldehydes and ketones in the presence of hydroxo complexes of platinum(II): An example of Lewis acid catalytic activity

Article abstract of DOI:10.1139/v01-067

The complex [(dppb)Pt(μ-OH)]₂(BF₄)₂ displays high catalytic activity in the thioacetalization of a variety of aldehydes and ketones with mercaptoethanol under very mild conditions. The reaction rate is greatly enhanced by

Full text of DOI:10.1139/v01-067

621
Thioacetalization of aldehydes and ketones in the
presence of hydroxo complexes of platinum(II): An
example of Lewis acid catalytic activity
Lorenzo Battaglia, Francesco Pinna, and Giorgio Strukul
Abstract: The complex [(dppb)Pt(µ-OH)]2(BF4)2 displays high catalytic activity in the thioacetalization of a variety of
aldehydes and ketones with mercaptoethanol under very mild conditions. The reaction rate is greatly enhanced by the
addition to the reaction mixture of magnesium perchlorate as drying agent and molar turnovers as high as 9700 can be
observed. The effect of different desiccating agents is also reported. The reactivity pattern observed, the similarity with
other reactions and NMR spectroscopic investigations confirm the possible role of the complex as Lewis acid catalyst
in promoting the reaction.
Key words: thioacetalization, catalysis, aldehydes, ketones, platinum complex.
Résumé : Le complexe [(dppb)Pt(µ-OH)]2(BF4)2 présente une activité catalytique élevée dans les réactions de thioacéta-
lisation d’une grande variété d’aldéhydes et de cétones par réaction avec le mercaptoéthanol, sous des conditions expé-
rimentales douces. La vitesse de la réaction est augmentée par l’addition au mélange réactionnel de perchlorate de
magnésium comme agent desséchant; on peut alors observer des taux de renouvellement chimique qui peut aller jus-
qu’à 9,700. On rapporte aussi l’effet de divers agents desséchant. Le type de réactivité observé, la similarité avec
d’autres réactions et les études par spectroscopie RMN confirment la possibilité que le complexe agit comme un cataly-
seur acide de Lewis pour promouvoir la réaction.
Mots clés : thioacétalisation, catalyseur, aldéhydes, cétones, complexe du platine.
[Traduit par la Rédaction] Battaglia et al. 625
Introduction
more prone to attack by the peroxidic oxidant. An essential
requirement to promote this kind of reactivity is the pres-
ence of a positive charge on the metal which, therefore, pos-
sesses a significant Lewis acidity. An example of this
behavior is shown in Scheme 1 which illustrates the mecha-
nism of the Baeyer–Villiger oxidation of ketones catalyzed
by [(P-P)Pt(µ-OH)]22+ complexes [9] (P-P = a variety of dif-
ferent disphosphines, including chiral ones for asymmetric
transformations (10)). The Lewis acidity of these complexes
The acetalization reaction is a process that is widely used
in organic synthesis to protect the carbonyl group of alde-
hydes and ketones (1) and for the synthesis of end products
(acetals), including enantiomerically pure compounds (see
for example ref. 2), that find practical application in the field
of synthetic carbohydrate (3), steroids (4), pharmaceuticals
and fragrances (5), and as polymers and copolymers (6).
This reaction is normally acid catalyzed, although the use of
transition-metal complexes as Lewis acid catalysts has been
occasionally reported in the literature (7). In the past two de-
cades we have extensively studied the properties of cationic
Pd(II) and Pt(II) complexes in a variety of oxidation reac-
tions using hydrogen peroxide as oxidant (for reviews on
this subject see ref. 8). A typical feature displayed by the
metal in the latter reactions is the ability to increase the re-
activity of the substrate by coordination thereby making it
Scheme 1.
Received September 14, 2000. Published on the NRC
Research Press Web site at http://canjchem.nrc.ca on
May 31, 2001.
G. Strukul wishes to dedicate this work to Professor Brian R.
James, mentor and friend of a lifetime.
Lorenzo Battaglia, Francesco Pinna, and Giorgio Strukul.1
Department of Chemistry, University of Venice, Dorsoduro
2137, 30123 Venezia, Italy.
1Corresponding author (telephone: +39 041 257 8551;
fax: +39 041 257 8517; e-mail: strukul@unive.it).
Can. J. Chem. 79: 621–625 (2001)
© 2001 NRC Canada
DOI: 10.1139/cjc-79-5/6-621

622
Can. J. Chem. Vol. 79, 2001
Table 1. Thioacetalization of different substrates with 2-
Scheme 2.
mercaptoethanol catalyzed by [(dppb)Pt(µ-OH)]2 (BF4)2.
Temperature Max conversion Time
Run Substrate
(°C)
(%)
(min)
1
2
3
4
5
6
7
8
Benzaldehyde
25
25a
82
82
82
0
0
62
57
9
80
58
21
1440
1450
600
500
1800
300
Propanal
Acetophenone
p-Anisaldehyde 82
Cyclohexanone 82
has been recently exploited to catalyze the acetalization of a
variety of aldehydes and ketones (11), where some unusual
selectivities with respect to ordinary Brønsted acids were
observed, especially in the case of α,β-unsaturated substrates
(12).
350
1500
2-Hexanone
82
In this paper we wish to report the first example of a tran-
sition-metal catalyzed thioacetalization reaction. This reac-
tion is potentially very useful in organic synthesis as, for
example, the use of 2-mercaptoethanol as the acetalizing
agent leads to the formation of 1,3-oxathiolanes (Scheme 2)
and opens an easy access to a class of chiral compounds that
can be obtained starting from every aldehyde or unsymmet-
rically substituted ketones.
Note: Experimental conditions: Pt (5 µmol), substrate (5 mmol), 2-
mercaptoethanol (5 mmol), 1,2-dichloroethane (2.2 mL).
aPt (0.05 mmol).
action without catalyst shows no conversion. Similar results
were observed using other aldehyde and ketone substrates,
with the exception of acetophenone where a much lower
conversion was observed (Table 1). Since no attempt was
made to remove water formed during the reaction (Scheme 2),
in all cases the reaction stops at equilibrium concentration,
preventing the achievement of higher conversions.
For this reason the reaction was tested in the presence of a
desiccating agent. This is not unusual for equilibrium reac-
tions forming water, for example Gorla and Venanzi (7e) in
their study on catalyzed acetalization reactions found the use
of molecular sieves very useful to maximize conversions and
reaction rates. In the present case, Mg(ClO4)2·2H2O was
added to the initial reaction mixture in 20% excess with re-
spect to the theoretical amount of water formed at full con-
version. At the reaction temperature used in the previous
experiments (82°C) the thioacetalization reaction is ex-
tremely fast (>99% conversion in 1 min) both for the cata-
lyzed and the non-catalyzed blank reaction. For this reason a
new series of catalytic tests was carried out at 25°C. The re-
sults for a variety of aldehydes and ketones are shown in Ta-
bles 2 and 3 where a comparison with the non-catalyzed
reaction is also reported.
As can be seen, in the case of aldehydes the reaction is al-
ways very fast and catalyst amounts as low as 0.01% with
respect to the substrate were used. A comparison with the
non-catalyzed reactions indicate that the catalytic effect is
not very pronounced except in the case of p- and m-
anisaldehyde, where the non-catalyzed reaction is consider-
ably slower. The case of ketones is different. In all cases the
catalytic effect is very strong (perhaps with the exception of
cyclohexanone). In a few hours a variety of ketones can be
converted almost quantitatively with the catalyst performing
8500–9700 turnovers, opening some interesting synthetic
perspectives.
Results and discussion
The complex used as catalyst in the present study is
[(dppb)Pt(µ-OH)]2(BF4)2. This cationic complex displays a
significant Lewis acidity as was already observed in the ca-
talysis of the above mentioned acetalization reactions (11,
12) and in the Baeyer–Villiger oxidation of ketones with hy-
drogen peroxide (9). The choice of this complex is due to
the fact that it proved to be the most active among the ho-
mologous complexes of Pt in both the acetalization and the
Baeyer–Villiger oxidation. Moreover, compared to homolo-
gous complexes of Pd, it is more thermally stable and can be
used as catalyst up to 90°C without any problems. It can be
easily obtained starting from the corresponding dichloro
complex by addition of 2 equiv of AgBF4 in acetone (13) ac-
cording to eq. [1]. However, we found that the reported syn-
thetic procedure (13) may lead to the adsorption of
significant amounts of HBF4 on the complex upon precipita-
tion. To avoid possible ambiguities in the catalytic tests, the
complex, dissolved in CH2Cl2, was extracted several times
with water until neutrality was attained.
Initially, the search for the best reaction conditions in the
thioacetalization reaction was carried out. To this purpose, 2-
mercaptoethanol was tested in the reaction with
benzaldehyde and a summary of the results obtained is re-
ported in Table 1. Initial tests were carried out with
benzaldehyde at 25°C using 0.05% equivalents of the
dimeric catalyst with respect to the substrate corresponding
to 0.1% Pt. At room temperature, no activity was observed
even increasing the equivalents of Pt to 1% (run 2). Upon in-
creasing the reaction temperature to 82°C, a quick reaction
takes place leading to about 60% conversion in about 10 h
and to the neat formation (>99% selectivity) of 2-phenyl-
1,3-oxathiolane. During the same reaction time, a blank re-
Other desiccating agents have been tested in the
thioacetalization of 2-butanone taken as the test reaction,
namely sodium sulfate, magnesium sulfate, and molecular
© 2001 NRC Canada

Battaglia et al.
623
Fig. 1. Effect of four desiccating agents on the thioacetalization
Table 2. Thioacetalization of aldehydes with 2-mercaptoethanol
in the presence of magnesium perchlorate.
of 2-butanone with 2-mercaptoethanol in the presence of
[(dppb)Pt(µ-OH)]2(BF4)2 as catalyst. Mg(ClO4)2·2H2O (circles),
Na2SO4 (diamonds), molecular sieves (triangles), MgSO4
(squares). Experimental conditions: Pt (2 µmol), 2-butanone
(20 mmol), 2-mercaptoethanol (20 mmol), 1,2-dichloroethane
(8.8 mL), Mg(ClO4)2·2H2O (1.555 g), Na2SO4 (0.341 g), molecu-
lar sieves (3.6 g), MgSO4 (0.413 g).
Substrate
With catalyst
Without catalyst
Conversion Time Conversion Time
(%)
(min) (%)
(min)
Propanal
Benzaldehyde
3-Chlorobenzaldehyde 96
p-Anisaldehyde
m-Anisaldehyde
Octanal
99
90
5
210
140
200
55
90
85
98
78
87
92
4
415
130
1650
1335
25
85
84
94
4
Note: Comparison between the catalyzed (by [(dppb)Pt(µ-OH)]2(BF4)2)
and the non-catalyzed reaction. Experimental conditions: Pt (2 µmol),
substrate (20 mmol), 2-mercaptoethanol (20 mmol), Mg(SO4)2·2H2O
(1.555 g), 1,2-dichloroethane (8.8 mL).
Table 3. Thioacetalization of ketones with 2-mercaptoethanol in
the presence of magnesium perchlorate.
Substrate
With catalyst
Without catalyst
Conversion
(%)
Time
(min)
Conversion
(%)
Time
(min)
2-Butanone
2-Hexanone
Cyclohexanone
Acetophenone
Phenylacetone
96
90
97
85
84
200
400
270
5400
1065
3
1
86
0
1260
1700
1080
5400
1260
Scheme 3.
2
Note: Comparison between the catalyzed (by [(dppb)Pt(µ-OH)]2(BF4)2)
and the non-catalyzed reaction. Experimental conditions: Pt (2 µmol),
substrate (20 mmol), 2-mercaptoethanol (20 mmol), Mg(SO4)2·2H2O
(1.555 g), 1,2-dichloroethane (8.78 mL).
sieves. The results are summarized in Fig. 1 and show that
Mg(ClO4)2·2H2O is by far the most effective desiccating
agent. Since all desiccants tested are based on poorly coordi-
nating anions, an interpretation of the data of Fig. 1 on this
basis seems unlikely. Indeed, they differ significantly in the
water absorption rate and, to a minor extent, in the water ab-
sorption capacity, in this respect magnesium perchlorate be-
ing the best option (14). This view may constitute a possible
explanation for the behavior shown in Fig. 1, where the dif-
ferent rates correlate with the absorption rate, while the
maximum conversions could be associated to different
amounts of residual water at the equilibrium. The possible
direct involvement of Mg2+ through the formation of soluble
species similar to the complex [(PPh3)2Pt(µ-O)]2LiBF4 as re-
ported by Sharp and co-workers (13a) seems less likely in
view of the very different behavior between magnesium per-
chlorate and magnesium sulfate observed in Fig. 1.
From Table 3, it appears that aliphatic ketones are more
reactive and their reactivity can be correlated to the induc-
tive effect of substituents as for example in the sequence:
2-butanone > phenylacetone > acetophenone. This seems to
suggest that the role of the catalyst can be associated to
Lewis acidity, where the electrophilicity of the carbonyl
compound is increased by coordination making it more
prone to nucleophilic attack by the alcohol (thiol). In this re-
spect, Scheme 1 provides a rationale for the understanding
of the mechanism with which the thioacetalization reaction
occurs. The similarities between the formation of the
hydroperoxyplatinum ketone complex and the process de-
picted in Scheme 3 are evident.
We tried to find some experimental evidence for the for-
mation of the intermediate indicated in Scheme 3. First of
all, the reaction between [(dppb)Pt(µ-OH)]22+ and 2-merca-
ptoethanol was carried out (Scheme 4). A formulation of the
new complex isolated as in Scheme 4 is supported by its
spectroscopic features. It shows in the solid-state a strong,
characteristic IR band at ~1090 cm–1 (BF4), a broad band at
3360 cm–1, and a weak band at 3521 cm–1. The latter can be
assigned respectively to the H-bonded and free O—H
stretching vibrations of coordinated 2-mercaptoethanol. Con-
sistently, in 1,2-dicholoroethane (DCE) solution only a weak
band at 3533 cm–1 can be observed. No bands are observed
in the region 2500–2600 cm–1 that can be assigned to
the presence of SH ligands. Conductivity measurements (1 ×
10–3 M in MeOH) are consistent with the presence of a 1:1
electrolyte (ΛM 91 Ω–1 mol–1 cm2) (15). In contrast to the
inequivalence of the two phosphorus donors, the 31P NMR
spectrum in CD3OD at 25°C shows only a sharp singlet at
15.82 ppm with a 1JP-Pt of 2904 Hz. When the temperature is
lowered the signal broadens significantly and, at –70°C, the
signal is so broad that it can hardly be distinguished from
the base line. These observations may be consistent with the
presence of a fast interchange equilibrium between the O
and S donors as depicted in Scheme 4 promoted by a revers-
© 2001 NRC Canada

624
Can. J. Chem. Vol. 79, 2001
Scheme 4.
ible displacement of the OH moiety by MeOD. Unfortu-
nately, the poor solubility of the new complex in solvents
such as dichloromethane and acetone did not allow to con-
firm this hypothesis in other solvents.
a Hewlett–Packard 5790A gas chromatograph equipped with
a 3390 automatic integrator. GC–MS measurements were
performed on a Hewlett–Packard 5971 mass selective detec-
tor connected to
a
Hewlett–Packard 5890 II gas
chromatograph. Identification of products was made with
GC or GC–MS by comparison with authentic samples.
Subsequently, the complex isolated from the previous re-
action was dissolved in a large amount of 1,2-dichloroethane
(the solvent used for the catalytic reactions) followed by ad-
dition of a 10-fold excess of p-anisaldehyde. The mixture
was allowed to react both at 25°C and at 65°C for 2 h, how-
ever, no new product formation was observed by GC analy-
sis. Isolation of the Pt species followed by spectroscopic
analysis indicated that its features were identical to those of
the starting complex. These observations are apparently in
contrast with the observed catalytic effects displayed by
[(dppb)Pt(µ-OH)]22+ and seem to indicate that the chelating
effect of 2-mercaptoethanol as indicated in Scheme 4 is
quite strong and is not reverted by the addition of a moder-
ate excess of a mild ligand such as an aldehyde (or a
ketone). However, it can be observed that under catalytic
conditions, the carbonyl compound is added before 2-
mercaptoethanol and in a much larger excess (1000–10 000
times with respect to the catalyst). In addition, the desiccat-
ing agent is present which allows the reaction to proceed at
room temperature. These conditions are practically impossi-
ble to meet on a stoichiometric basis. In any case, the results
reported in the above experiments show that the bridging
hydroxy ligand can be promptly opened under catalytic con-
ditions and support the plausibility of Scheme 3 as the acti-
vating process.
Materials
Solvents were dried and purified according to standard
methods (14). Aldehyde and ketone substrates, 2-
mercaptoethanol employed in the thioacetalization reactions
and the desiccating agents (Mg(ClO4)2·2H2O, Na2SO4, mo-
lecular sieves 3A, MgSO4) were commercial products
(purum or puriss quality) used without purification.
The complex [(dppb)Pt(µ-OH)]2(BF4)2 was prepared ac-
cording to literature procedures (13).
Thioacetals used as standards for gas chromatography in
the individual catalytic reactions were synthesized from the
starting aldehyde–ketone (20 mmol) and the stoichiometric
amount of 2-mercaptoethanol in 25 mL DCE (1,2-
dicholoroethane), to which 0.2 mmol PTSA (p-
toluenesulfonic acid) were added under N2 with stirring. The
solution containing the acetal was used for qualitative identi-
fication in the GC analysis.
Reaction between [(dppb)Pt(µ-OH)]2(BF4)2 and 2-
mercaptoethanol
The complex [(dppb)Pt(µ-OH)]2(BF4)2 (120 mg,
0.083 mmol) was dissolved in 20 mL of dry N2 saturated
1,2-dichloroethane. 2-Mercaptoethanol (11.6 µL, 0.166 mmol)
was added under N2 and the solution was stirred for 2 h at
room temperature. Addition of 20 mL of Et2O lead to the
precipitation of a white solid, which was filtered, washed
with Et2O, and dried in vacuo. (Yield: 92%). Anal. calcd. for
C30H33BF4OP2PtS: C 45.87, H 4.23; found: C 46.01, H 4.11.
In conclusion, the platinum complex reported here ap-
pears to be a very interesting Lewis acid catalyst for the
thioacetalization of a variety of aldehydes and ketones show-
ing productivities that are attractive also for synthetic pur-
poses. The easy modification of this class of complexes with
chiral diphosphines seems to open also a viable access to the
asymmetric transformation.
Catalytic reactions
Experimental
These were carried out in a 25-mL round-bottomed flask
equipped with a stopcock for vacuum–N2 operations and a
side-arm fitted with a screw-capped silicone septum to allow
sampling. Constant temperature (±0.1°C) was maintained by
water circulation through an external jacket connected with a
thermostat. For reactions carried out at temperatures >25°C
the reaction vessel was equipped with a reflux condenser
and heating was ensured by a thermostatted external oil
bath. Stirring was performed by a teflon-coated bar driven
externally by a magnetic stirrer.
Apparatus
Infrared spectra were taken on a Nicolet FT-IR Magna
750 and on a Digilab FTS 40 interferometer either in solid
(KBr pellets) or in CH2Cl2 solution using CaF2 windows. 31
P
NMR spectra were recorded on a Bruker AC 200 spectrome-
ter operating in FT mode, using as external reference 85%
H3PO4. Conductivity measurements were performed on a
Radiometer instrument using 1 × 10–3 M solutions in MeOH
at 25°C. Gas chromatographic measurements were taken on
© 2001 NRC Canada

Battaglia et al.
625
4. J.R. Bull, J. Floor, and G.J. Kruger. J. Chem. Res. Synop. 224
(1979).
The following general procedure was followed: the re-
quired amount of catalyst was placed solid in the reactor
which was evacuated and filled with N2. Nitrogen-saturated
solvent was added followed by aldehyde–ketone in the ap-
propriate amount under N2 flow. After thermostatting at the
required temperature for a few min, 2-mercaptoethanol was
injected through the septum and time was started.
All reactions were monitored with GC by direct injection
of samples taken periodically from the reaction mixtures
with a microsyringe. Separation of the products was per-
formed on 25 m capillary columns using a flame ionization
detector. Prior quenching of the catalyst using an excess of
LiCl showed no differences in randomly selected analyses.
5. (a) K.A.M. Walker. U.S. Patent 4 150 153 (1979); (b) K.
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Acknowledgements
The financial support of MURST (Cofin 98) is gratefully
acknowledged.
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© 2001 NRC Canada