The anomalous reactivity of the bis(dibutylstannylene) acetal of pentaerythritol: A case of triple activation

Article abstract of DOI:10.1016/S0008-6215(01)00034-9

The only dibutyltin derivative of pentaerythritol which is observed by refluxing with dibutyltin oxide in methanol is a bis(dibutylstannylene) acetal. This is converted to the expected dibenzyl ether with benzyl bromide, in the presence of tetraethylammon

Full text of DOI:10.1016/S0008-6215(01)00034-9

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Carbohydrate Research 331 (2001) 327–329
Note
The anomalous reactivity of the bis(dibutylstannylene)
acetal of pentaerythritol: a case of triple activation
Serge David*
Institut de Chimie Mole´culaire, Baˆteau 420, Uni6ersite´ de Paris-Sud, F-91405 Orsay, France
Received 12 December 2000; accepted 24 January 2001
Abstract
The only dibutyltin derivative of pentaerythritol which is observed by refluxing with dibutyltin oxide in methanol
is a bis(dibutylstannylene) acetal. This is converted to the expected dibenzyl ether with benzyl bromide, in the
presence of tetraethylammonium bromide in boiling toluene, but benzoylation at room temperature gives a
tribenzoate. A mechanism is suggested to account for this triple activation. © 2001 Elsevier Science Ltd. All rights
reserved.
Keywords: Pentaerythritol; Stannylenes; Triple activation
There is current interest in the utilization of
partially protected pentaerythritol derivatives
to prepare conjugates of organic compounds
with various carrier molecules.1 This led us to
examine the course of derivatization by the
stannylene method.2 This approach allows a
strictly regiospecific substitution at one of the
oxygen atoms in a diol. In unprotected
oligosaccharide glycosides the substitution is
again regiospecific, despite the great number
of potentially reactive oxygen atoms.3 How-
ever, application of the method to pentaery-
thritol revealed unexpected anomalies.
Refluxing a mixture of pentaerythritol with
two equivalents of dibutyltin oxide in
methanol, followed by evaporation to dryness
gave the bis(dibutylstannylene) acetal of pen-
taerythritol. From what is known about the
relative instability of monomeric 2,2-dibutyl-
1,3,2-dioxastannolane with respect to its
oligomers,4 this product is most probably a
polymer. As expected, treatment with benzyl
bromide in the presence of tetra-
methylammonium bromide in boiling toluene5
afforded the ether 6 in 70% yield, identical
with a specimen prepared by another route.
This ‘one-pot’ preparation from pentaery-
thritol appears to be the most convenient ac-
cess to ether 6, as the described procedure
involving benzylation of the benzylidene
derivative requires three steps.6 Although ben-
zylation of stannylenes is normally possible in
polar solvents at 100 °C without a catalyst, we
have observed no reaction under these condi-
tions in N,N-dimethylformamide solution.
By analogy, we expected that the benzoyla-
tion of the bis(dibutylstannylene) acetal at
room temperature would yield a dibenzoate in
an efficient way. In fact, the reaction of 1.7
mmol of benzoyl chloride with 1 mmol of
stannylene gave a 3:1 mixture of the triben-
* Tel.: +33-1-69155269; fax: +33-1-69154715.
E-mail address: serdavid@icmo.u-psud.fr (S. David).
0008-6215/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(01)00034-9

328
S. Da6id / Carbohydrate Research 331 (2001) 327–329
zoate 1 (as the main constituent) with the
expected dibenzoate 2 as a minor product.
Practically all the benzoyl chloride was con-
sumed, while 43% of the starting material had
not reacted. Thus, it appears that the third
benzoylation step was more rapid than the
first ones. The same experiment with 3.4 or 6.9
mmol of benzoyl chloride gave only the
tribenzoate 1, which was obtained in 70%
yield, without any di- or tetrabenzoate7 5.
We must first dismiss the explanation of a
common supplementary esterification by the
reagent in great excess. Such a reaction would
necessitate basic conditions, and be generally
much slower at room temperature than the
benzoylation of hydroxyl groups activated by
conversion into dibutylstannylene acetals.
However, in our case, the medium is neutral
and the reaction is very fast, being complete in
less than 5 min at room temperature. This is
the characteristic reactivity of the stannylene
acetals.
evidence for its existence. Refluxing
equimolecular amounts of dibutyltin oxide
and pentaerythritol gave a mixture which af-
forded only the tribenzoate 1 on benzoylation.
This behavior contrasts with that of polyhy-
droxylated oligosaccharides, which are acti-
vated at only one site when treated with an
equimolecular amount of dibutyltin oxide. We
have shown elsewhere5 that mixtures of stan-
nylenes undergo a rapid intermolecular equili-
bration in favor of the most stable derivative.9
Thus, our observation might be explained by
the greater stability of the polymer.
We suggest the following mechanism for
this triple activation. In the likely8 intermedi-
ate 7, intramolecular coordination would give
the stannoxane 8, which may be reactive as
such, or be converted to some kind of reactive
stannoxane, for instance after disproportiona-
tion and elimination of dibutyldichlorotin.
Apparently these intermediates do not form,
or are not reactive under the conditions of
benzylation (111 °C, ionic catalyst).
We can now reinvestigate the course of the
stannylenation of pentaerythritol with the
knowledge we have of its reactions. Although
the formation of a monostannylene derivative
appears likely as a first step, we have found no
1. Experimental
General.—Samples were examined on Silica
Gel TLC plates (E. Merck), with 1:1
petroleum ether–EtOAc as eluent, unless oth-
erwise stated, and inspected under UV light at
254 nm. Preparative chromatographic separa-
tions were achieved with open columns filled
with silica gel (40 mL per gram of mixture).
1H NMR spectra (250 MHz) were recorded in
chloroform-d in the presence of Me4Si and
chemical shifts are reported in Table 1. Aro-
matic protons are not tabulated, the signals
for all derivatives appear at 7.40–7.60 and
8.02 ppm.
Table 1
1H NMR spectra of pentaerythritol derivatives 1–6
Protons
1, 2
3
4
OH
Others
1
2
3
4.60
4.49
4.50
4.60
3.73
4.34
3.70
3.73
3.70
2.85
3.04
2.04
(Ac)
4.50
2.07
4
4.85
4.31
4.70
3.65
4.06 (d), 4.36 (d)
J 12 Hz
4.70
3.58
(PhCH)
Preparation of the dibutyltin deri6ati6e of
pentaerythritol.—A mixture of pentaerythritol
(1.36 g, 10 mmol) and dibutyltin oxide (5.0 g,
5
6
4.70
3.58
2.69

S. Da6id / Carbohydrate Research 331 (2001) 327–329
329
and the mixture was stirred for 5 min at rt.
Dissolution was then complete. Processing of
the mixture and chromatography conducted
as above, separated first the tribenzoate (373
mg, 0.83 mmol), Rf 0.5. Extraction of the
column with EtOAc; followed by chromatog-
raphy (1:1 petroleum ether–EtOAc) gave the
crystalline dibenzoate 2 (108 mg, 0.31 mmol),
mp 75 °C, Rf 0.30, identical to a sample pre-
pared as described below.
Preparation of dibenzoate 2 from benzyli-
dene-pentaerythritol.—Benzoylation of ben-
zylidene–pentaerythritol (0.6 g, 2.68 mmol)
with BzCl (0.75 mL) in pyridine (3 mL) gave,
after the usual working up, the dibenzoate 4
(891 mg, 77%), mp 122 °C (MeOH). A solu-
tion of this compound (2.43 g, 5.6 mmol) in
AcOH (25 mL) and water (15 mL) was kept at
90 °C for 3 h. After evaporation of the sol-
vents, chromatography of the residue (1:1
petroleum ether–EtOAc) first gave the acetate
3 (615 mg) and then the crystalline dibenzoate
2 (731 mg, 38%), mp 75 °C. This compound
could not be crystallized from common sol-
vents. Anal. Calcd for C19H20O6: C, 66.28; H,
5.81; Found: C, 66.44; H, 6.01.
20 mmol) was refluxed in methanol for a few
hours. The solvent was removed by evapora-
tion and the glassy residue was dried first by
keeping for 1 day at 40 °C under diminished
pressure, and then by coevaporation with tol-
uene. The product was stored in a dessicator
(P2O5) but did not appear to be hygroscopic.
2,2-Bis(benzyloxymethyl)-1,3-propanediol
(6).—A suspension of the above stannylene
derivative (0.6 g, 1 mmol) in toluene (10 mL)
in the presence of BnBr (0.5 mL, 4 mmol) and
tetraethylammonium bromide (135 mg) was
heated at reflux for 4 h, cooled to rt and
stirred with water (20 mL). Evaporation of the
organic phase gave a residue from which was
separated by chromatography (EtOAc) the
crystalline dibenzyl ether 6 (211 mg, 70%), mp
67–70 °C, raised to 73 °C by one crystalliza-
tion from petroleum ether, Rf 0.35. This was
identical with a sample prepared according to
Ref. 6.
3 - O - Benzoyl - 2,2 - bis(benzoyloxymethyl)-
1,3-propanediol (1).—Benzoyl chloride (0.8
mL, 6.9 mmol) was added to a suspension of
the above stannylene derivative (0.6 g, 1
mmol) in toluene (5 mL). After 10 min at rt,
water (10 mL) was added to the clear solution,
and the mixture was stirred vigorously for 4 h,
while the medium was kept neutral by the
addition of a sodium hydrogencarbonate solu-
tion. The organic layer was separated, and the
solvent was removed by evaporation. Chro-
matography of the residue (706 mg), with 8:1,
4:1, 2:1, and 1:1 petroleum ether–EtOAc mix-
tures as eluent, separated the tribenzoate 1 as
a glass (318 mg, 70%), Rf 0.35 (2:1 petroleum
ether–EtOAc). Anal. Calcd for C26H24O7: C,
69.64; H, 5.35. Found: C, 69.45; H, 5.57.
A similar experiment conducted with 3.4
mmol of BzCl per mmol of stannylene gave
the same tribenzoate as the only product
which could be detected on a TLC plate.
2,2-Bis(benzoyloxymethyl)-1,3-propanediol
(2).—To a suspension of the above stannylene
derivative (1.2 g, 2 mmol) in dry toluene (10
mL), BzCl (0.40 mL, 3.4 mmol) was added,
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