Tin-mediated equilibration of the benzoate esters of methyl 4,6-O- benzylidene-α-D-glucopyranoside

Article abstract of DOI:10.1016/S0040-4039(99)02115-2

The selective dibutyltin oxide-mediated benzoylation of methyl 4,6-O- benzylidene-α-D-glucopyranoside at position 2 is not a post-acylation phenomenon as is the case with the equivalent benzoylation of phenylethyleneglycol. ¹H NMR temperature s

Full text of DOI:10.1016/S0040-4039(99)02115-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 543–546
Tin-mediated equilibration of the benzoate esters of methyl
4,6-O-benzylidene-α-D-glucopyranoside
Martin W. Bredenkamp ∗ and Hendrik S. C. Spies
Department of Chemistry, Stellenbosch University, Private Bag X1, Matieland, 7602 South Africa
Received 30 September 1999; accepted 10 November 1999
Abstract
The selective dibutyltin oxide-mediated benzoylation of methyl 4,6-O-benzylidene-α-D-glucopyranoside at po-
sition 2 is not a post-acylation phenomenon as is the case with the equivalent benzoylation of phenylethyleneglycol.
1H NMR temperature studies have shown that such equilibration occurs only above 85°C in toluene-d8 for the
glucopyranoside. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: acylation; carbohydrates; NMR; tin compounds.
The selectivity in acylation of phenylethylene glycol mediated by dibutyltin oxide has been very
elaborately shown1 to occur when the resultant dibutylchlorostannyl group is removed by quenching.
Prior to quenching, the chlorostannyl group, in an equilibration process, exchanges places with the acyl
group via a proposed stannyl glycol ortho ester intermediate (Scheme 1). The equilibrium, which is
completely functional at ambient temperature, favours the isomer 1 due to the greater steric demands of
the dibutylchlorostannyl group relative to the acyl group. On quenching, the selectivity in favour of the
ester of the secondary alcohol is further enhanced by the better accessibility the quenching agent has to
the chlorostannyl group at the primary position.
Scheme 1.
In the light of this process of equilibration, the selectivity of acylation in sugars raises a question.
Dibutyltin oxide-mediated benzoylation of methyl 4,6-O-benzylidene-α-D-glucopyranoside (3), for ex-
ample (Scheme 2), yields the 2-benzoate 6 on aqueous work up.2 It would, however, be expected that
∗
Corresponding author. Fax: 27-21-808-3360; e-mail: mwb@maties.sun.ac.za (M. W. Bredenkamp)
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(99)02115-2
tetl 16043

544
the 3-benzoate 7 should be the main product for three reasons: (i) the bulkier dibutylchlorostannyl group
should be more stable at the 2-O-position (5) since the axiality of the anomeric position allows for more
space at position O-2; (ii) the quenching agent should access the 2-O- (5) rather than the 3-O-stannyl
group (4) better for steric reasons and (iii) the axial anomeric oxygen atom (5) should stabilise the 2-
O-stannyl group by chelation, whereas chelation by the oxygen atom at position 4 (4) is less favourable
because it is equatorial. This implies that: (i) there is no equilibration of the chlorostannyl intermediate
at ambient temperature, after tin mediated-benzoylation has occurred, or (ii) equilibration favours the
3-chlorostannyl isomer 4 sufficiently to yield 6 on quenching, or (iii) quenching is very selective towards
the 3-chlorostannyl isomer 4. We herewith present our investigation into this anomaly.
Scheme 2.
In order to obtain reference compounds, methyl 4,6-O-benzylidene-α-D-glucopyranoside (3)3 was
treated with benzoyl chloride in pyridine yielding 6 and 7 and the 2,3-dibenzoate 8.4 The mixture was
easily separated using flash chromatography. The 1H and 13C NMR chemical shifts are given in Tables 1
and 2, respectively. The benzoylchlorostannyl intermediate (4 and/or 5) was then prepared as in Scheme
2, the only difference being the exchange of the benzene for chloroform before benzoylation to best
1
simulate the conditions used by Roelens1 on phenylethyleneglycol. Both the H and 13C NMR of the
intermediate reveal a species that is almost identical to compound 65 without the OH signal and with
satellites at the H-3 signal indicating 3J-coupling to 119Sn and 117Sn. Two sets of butyl signals are also
observed (Tables 1 and 2). The 1H NMR spectrum well characterises the tin complex 4 without a trace
of signals that may be assigned to the isomer 5. As quenching agent the bulky pivaloyl chloride was
used to enhance selectivity for the 2-O-position on the assumption of equilibration between 4 and 5.
The 2-O-benzoyl-3-pivaloate 96 was formed without a trace of the 3-O-benzoyl-2-pivaloate 10. This
result was confirmed twice, firstly by the reversed order of acylation (PivCl then BzCl) by dibutyltin

545
oxide-mediation, yielding the isomer 10.6 Secondly, a good yield of the 3-benzoate 7 was obtained by
dibutyltin oxide-mediated trimethylsilylation, followed by benzoylation and then desilylation.
Table 1
Selected 1H NMR chemical shifts (CDCl3) of derivatives of methyl 4,6-O-benzylidene-α-D-
glucopyranosidea
Table 2
Selected 13C NMR chemical shifts (CDCl3) of derivatives of methyl 4,6-O-benzylidene-α-D-
glucopyranosidea
At this stage, no evidence for an equilibration process had been obtained. Yet the possibility of
its existence at ambient temperature had not been disproved. If the 2-O-chlorostannyl-3-O-benzoyl
intermediate 5 could be prepared along an alternate route and an equilibrium existed that greatly favoured
1
the isomeric intermediate 4, then the latter should be observed as the only compound by H NMR
as before. Such an alternate preparation could be obtained by treating the 3-benzoate 7 with 0.5 mol
equivalents of bis(dibutylchlorotin) oxide in refluxing toluene. Before this reaction was tried, it was first
performed on the isomeric 2-benzoate 6 as a control reaction. Surprisingly this yielded a 1:1 mixture
1
of 4 and 5, respectively, as observed by H and 13C NMR. The equilibrating role of this process was
confirmed by similar results with 1 and 2 mol equiv. of (Bu2ClSn)2O on 6 and 1 mol equiv. on 7.
Quite clearly the equilibrating role that (Bu2ClSn)2O plays implies that the stannylene species involved
is not the same as that derived from Bu2SnO/BzCl, or alternately, temperature plays a role. The reflux
temperature of toluene (111°C) was used to incorporate the chlorostannyl species into 6 and 7 which
already contained benzoyl esters, whereas ambient temperature was not exceeded after the addition of
benzoyl chloride to the Bu2SnO complex of 3. An NMR temperature study was thus conducted on a fresh
sample of 4 generated by complexing Bu2SnO onto 3 in refluxing toluene followed by the addition of

546
BzCl at ambient temperature. The toluene was removed and a sample dissolved in toluene-d8 in an NMR
tube. As before the sample consisted of a tin complex of the 2-benzoate 4. This did not change at even
85°C for 35 min in the NMR probe. The tube was then heated at 108°C for 75 min in an oil bath, during
which time isomerisation occurred furnishing a 2:1 mixture of the 2-benzoate 4 relative to the 3-benzoate
5. This isomer mixture changed to 1:1 after 16 h of heating. Some debenzoylation also occurred.
Post-acylation equilibration is clearly not an ambient temperature process for the dibutyltin oxide-
mediated benzoylation of methyl 4,6-O-benzylidene-α-D-glucopyranoside (3) as is the case with phenyl-
ethylene glycol.1 It is likely that other sugar derivatives, due to the rigidity of the ring structures, will also
experience post-acylation equilibration only at elevated temperatures. We are now investigating sugar cis-
diols and also sugar tri- and tetrols in this respect.
Acknowledgements
The Foundation for Research Development and the University of Stellenbosch is thanked for financial
support.
References
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2. (a) Holzapfel, C. W.; Koekemoer, J. M.; Marais, C. F. S. Afr. J. Chem. 1984, 37, 19. (b) David, S.; Thieffry, A. J. Chem. Soc.,
Perkin Trans. 1 1979, 1568.
3. Bredenkamp, M. W.; Flowers, H. M.; Holzapfel, C. W. Chem. Ber. 1992, 125, 1159.
4. Ohle, H.; Spencker, K. Ber. 1928, 61B, 2387.
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species.
6. This structure was determined unambiguously by means of observing long range correlations between the relevant carbonyl
13C signals and the sugar ring protons using XHLR experiments: Reynolds, W. F.; McLean, S.; Perpick-Dumont, M.;
Enríquez, R. G. Magn. Reson. Chem. 1989, 27, 162.
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