SCHEME 1. Selective O-Mon oben zyla tion of Diols
via Sta n n ylen e Aceta ls
A Mor e Con ven ien t a n d Gen er a l P r oced u r e
for O-Mon oben zyla tion of Diols via
Sta n n ylen es: A Cr itica l Reeva lu a tion of
th e Bu 2Sn O Meth od
Alessandro B. C. Simas,* Karla C. Pais, and
Angelo A. T. da Silva
SCHEME 2. Syn th esis of m yo-In ositols 5 a n d 6
Universidade Federal do Rio de J aneiro, Nu´cleo de
Pesquisas de Produtos Naturais (NPPN), Laborato´rio
Roderick A. Barnes, Ilha da Cidade Universita´ria, CCS,
bloco H, Rio de J aneiro RJ 21941-590, Brazil
abcsimas@nppn.ufrj.br
On inspection of representative examples within the
vast collection of data in the literature dealing with the
use of stannylene acetals, we noticed an uncertainty on
the conditions actually needed for both the tin intermedi-
ate generation and, more importantly, its reaction with
alkylating agents such as BnBr. As the following discus-
sion demonstrates, such indecision does not seem to be
reasonable whatsoever. Apparently, it is not related to
the molecular diversity of the suitable substrates.
First, we concluded that the stannylene intermediate
formation does not require H2O removal (e.g., by use of
Dean-Stark apparatus), as it is observed in most of the
works in the literature.4,5 A simple reflux of the reactants
in CH3OH/toluene, followed by careful evaporation of the
solvents suffices for the reactions of both cyclic substrates
(bearing either cis-diol or trans-diol moieties) and acyclic
ones, as the following results will confirm. This aspect is
particularly important if it is taken into account that the
unnecessary use of the Dean-Stark apparatus requires
bath temperatures well above the reflux ones (140-150
°C in the case of toluene as solvent). So, when subjected
to the mentioned conditions, myo-inositols 4 and 5 were
converted to stannylene acetals 7 and 8 (Figure 1),
respectively.
Received December 3, 2002
Abstr a ct: A more consistent, straightforward, and eco-
nomical protocol for generation of stannylene species and
their reaction with BnBr leading to products of O-monoben-
zylation of diols has been set. It has shown to be specially
indicated for substrates bearing vicinal trans 1,2-diol moi-
eties on cyclohexane backbones, which are more resistant
to these transformations. Such protocol has been successfully
applied to myo-inositol derivatives and acyclic diols.
The introduction of tributyltin ethers and dibutylstan-
nylene acetals derived from alcohol and diol moieties,
respectively, provided a major leap to carbohydrate
chemistry, most notably.1 On reacting with activated
alkyl halides (the main use of these organometallic
intermediates), they combine an adequate nucleophilicity
with a negligible basicity. Stannylene acetals 2 (Scheme
1) are produced by reaction of diol moieties 1 and Bu2-
SnO.1,2 Such species may undergo substitution to 3 under
essentially neutral conditions. Remarkable features of
these reactions are the regiochemical (substitution on
primary hydroxyl groups prevails over those on secondary
or tertiary ones) and stereochemical (equatorial hydroxyl
groups, and not axial ones, react preferentially) controls
that they enable. Besides, the Bu2SnO method is able to
selectively afford O-monosubstituted diol moieties even
in the presence of other unprotected hydroxyl groups.
Due to such assets, this powerful methodology is not
paralleled by anionic chemistry, which usually leads to
mixtures of isomers.1
For the benzylation of the tin species 7, we chose the
Veyrie`res-David conditions.6 Reaction of this organo-
metallic compound with BnBr in toluene in the presence
of Bu4NBr (0.2 molar equiv; condition A of stannylene
alkylation) occurred uneventfully to provide 5 (Table 1,
entry 1). It is not necessary to employ either stoichio-
metric or excess amounts of ammonium halide additive,7
(4) (a) Ramos, D.; Rollin, P.; Klaffke, W. J . Org. Chem. 2001, 66,
2948. (b) Bernardi, A.; Arosio, D.; Manzoni, L.; Micheli, F.; Pasquarello,
A.; Seneci, P. J . Org. Chem. 2001, 66, 6209. (c) Hanessian, S.; Huynh,
H. K.; Reddy, G. V.; Duthaler, R. O.; Katopodis, A.; Streiff, M. B.; Kinzy,
W.; Oehrlein, R. Tetrahedron 2001, 57, 3281. (d) Mart´ınez-Bernhardt,
R.; Castro, P. P.; Godjoian, G.; Gutie´rrez, C. G. Tetrahedron 1998, 54,
8919. (e) Hanessian, S.; Pan, J .; Carnell, A.; Bouchard, H.; Lesage, L.
J . Org. Chem. 1997, 62, 465. (f) Riley, A. M.; J enkins, D. J .; Potter, B.
V. L. J . Am. Chem. Soc. 1995, 117, 3300. (g) J enkins, D. J .; Potter, B.
V. L. Carbohydr. Res. 1994, 265, 145. (h) Nagashima, N.; Ohno, M.
Chem. Lett. 1987, 141.
(5) The exceptions almost invariably deal with the preparation of
stannylenes from cis diol moieties on furanoside backbones, following
the pioneering work of Moffatt’s group: Wagner, D.; Verheyden, J . P.
H.; Moffatt, J . G. J . Org. Chem. 1974, 39, 24. Boger, D. L.; Ichikawa,
S.; Zhong, W. J . Am. Chem Soc. 2001, 123, 4161. Danishefsky, S. J .;
Hungate, R.; Schulte, G. J . Am. Chem. Soc. 1988, 110, 7434.
(6) (a) David, S.; Thieffry, A.; Veyrie`res, A. J . Chem. Soc., Perkin
Trans. 1 1981, 1796. (b) Veyrie`res, A. J . Chem. Soc., Perkin Trans. 1
1981, 1629.
In the course of our studies on inositol chemistry, we
were required to prepare large amounts of tetrabenzyl
ethers 6a and 6b (Scheme 2). After some disappointing
results of direct dibenzylation of tetrol 4 via (bis)stan-
nylene acetals,3 we realized that the stepwise process
(through triol 5) would yield a more consistent route to
those materials. However, the early work with these two
reactions indicated that there was some space for pro-
cedure improvement. The development of a protocol for
general application was clearly demanded.
(1) David, S.; Hanessian, S. Tetrahedron 1985, 41, 643.
(2) Auge´, C.; David, S.; Veyrie`res, A. J . Chem. Soc., Chem Commun.
1976, 375.
(3) Offer, J . L.; Voorheis, H. P.; Metcalfe, J . C.; Smith, G. A. J . Chem.
Soc., Perkin Trans. 1 1992, 953.
10.1021/jo026794c CCC: $25.00 © 2003 American Chemical Society
Published on Web 05/29/2003
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J . Org. Chem. 2003, 68, 5426-5428