Selective monosulfonylation of internal 1,2-diols catalyzed by di-n- butyltin oxide

Article abstract of DOI:10.1016/S0040-4039(00)00500-1

The reaction of internal 1,2-diols with catalytic n-Bu₂SnO, p-TsCl (1.05 equiv.) and Et₃N (1.1 equiv.) led to selective monotosylation. In the case of cyclic substrates, the cis-1,2-diol moiety appeared best suited for optimal results, supporting the intermediacy of a five-membered chelate. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00500-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 3773–3776
Selective monosulfonylation of internal 1,2-diols catalyzed by
di-n-butyltin oxide†
Michael J. Martinelli,∗ Rajappa Vaidyanathan ∗ and Vien Van Khau
Chemical Process R&D, Lilly Research Laboratories, Lilly Corporate Center, Eli Lilly and Company, Indianapolis,
IN 46285-4813, USA
Received 13 February 2000; revised 17 March 2000; accepted 20 March 2000
Abstract
The reaction of internal 1,2-diols with catalytic n-Bu2SnO, p-TsCl (1.05 equiv.) and Et3N (1.1 equiv.) led to
selective monotosylation. In the case of cyclic substrates, the cis-1,2-diol moiety appeared best suited for optimal
results, supporting the intermediacy of a five-membered chelate. © 2000 Elsevier Science Ltd. All rights reserved.
The selective monofunctionalization of diols has been of considerable interest in organic synthesis.
Since Shanzer first reported it,1 the monoderivatization of diols via their stannylene acetals has been
explored and reviewed thoroughly.2 Typically, the diol 1 is treated with a stoichiometric amount
of n-Bu2SnX, where X=O3 or (OMe)2,4 with removal of water or methanol to afford the desired
stannylene acetal 2. The stannylenes then undergo selective alkylation, acylation, sulfonylation, and
phosphorylation, usually at the primary position, or silylation with variable regioselectivity (Scheme
1).5 The principal limitations of these methods are the reaction rate and the unavoidable production of a
stoichiometric amount of n-Bu2SnO, which is usually separable only by chromatography.
Scheme 1.
We recently described a convenient protocol for the primary selective sulfonylation of terminal 1,2-
diols using catalytic n-Bu2SnO in conjunction with stoichiometric Et3N.6 The reactions were extremely
rapid, selective and high yielding. We report herein an extension of this method to the selective
monotosylation of internal 1,2-diols.
Table 1 lists various examples of internal 1,2-diols that were subjected to the n-Bu2SnO-catalyzed
tosylation reaction. In the case of cyclic 1,2-diols, significant rate differences were observed between the
∗
†
Corresponding authors.
We would like to dedicate this manuscript to Professor Jose Barluenga on the occasion of his 60th birthday.
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00500-1
tetl 16779

3774
catalyzed and uncatalyzed versions. For example, cis-cyclopentane-1,2-diol was efficiently tosylated in
the presence of catalytic n-Bu2SnO within 45 min to afford the desired monotosylate in 97% yield.
The corresponding uncatalyzed reaction went to approximately 13% conversion in 4 h (entry 1). A
similar rate enhancement was observed in the case of cis-cyclohexane-1,2-diol (entry 3). The reactions
of the corresponding trans-diols were much slower under the same conditions, and no significant rate
acceleration was observed with added n-Bu2SnO (entries 2 and 4). These results may be rationalized by
invoking the intermediacy of a five-membered ring stannylene acetal. The formation of such a species
would be more facile in the case of cis-1,2-diols than trans-1,2-diols. Interestingly, the tosylation of
hydrobenzoin led to the formation of trans-stilbene oxide in addition to the desired monotosylate. The
corresponding uncatalyzed reaction was also much slower in this case (entry 5). Sulfonylation of diethyl
tartrate under the n-Bu2SnO-mediated conditions led to a mixture of mono- and bis-tosylated products,
the latter arising presumably due to the coordination of tin to the ester oxygen.
Table 1
Mono-sulfonylation of 1,2-diols catalyzed by di-n-butyltin oxide
We then sought to expand the scope of this reaction to carbohydrate examples (α- and β-methyl-D-
xylose, Scheme 2). If the hypothesis of a five-membered intermediate were correct, one would expect
the α-anomer 3 to undergo preferential tosylation at the 2-position to afford 5. However, when the
n-Bu2SnO-catalyzed tosylation of α-methyl-D-xylose 3 was run in CH2Cl2, the conversion was low
(25%), and the predominant product was the 2,4-bis-O-tosylate (6). Similar results were obtained in the
absence of n-Bu2SnO. We reasoned that this was due to the higher solubility of the monotosylates 4
and 5 (compared to the starting material) in CH2Cl2. However, when the reaction was carried out in
dioxane,7 the 2-O- and 4-O-tosylated products (5 and 4, respectively) were obtained in 70% overall yield

3775
(77:23). This is in contrast to the results of Tsuda and co-workers who observed a preponderance of the
4-O-tosylate 4 when they treated the stannylene acetal derived from α-methyl-D-xylose with p-TsCl and
DMAP (cat.) in dioxane (Scheme 2).8
Scheme 2.
This trend may be explained as follows: We have already shown that an α-chelatable moiety should be
present for efficient catalysis of tosylations by n-Bu2SnO.6a For cyclic compounds, we have demonstrated
that this α-chelatable moiety should be cis to the hydroxy group (Table 1). In the case of the α-anomer
3, one may envision a five-membered intermediate arising out of tin coordination to the methoxy and
2-hydroxy groups (11, Scheme 3), thereby leading to tosylation at the 2-position to afford 5. The 4-
O-tosylate 4 may be formed either via the six-membered stannylene acetal intermediate 12, or via
an uncatalyzed reaction. Since five-membered rings are kinetically favored over six-membered rings,
one would expect 11 to be formed faster than 12, leading to the observed product distribution. On the
other hand, the product distribution observed by Tsuda and co-workers may be attributed to the greater
contribution of intermediate 12, where the 4-O–Sn bond is the most reactive to a bulky electrophile for
steric reasons.
Scheme 3.
The β-anomer 7, on the other hand, underwent tosylation preferentially at the 4-position to furnish
8, consonant with Tsuda’s results (Scheme 2); however, the conversion was low. In this case, the
trans relationship between the methoxy and 2-hydroxy groups would preclude the formation of a five-
membered chelate, and hence the 2-O-tosylate would not be formed. Moreover, the formation of the
six-membered stannylene acetal 13 via tin coordination to the 4- and 2-hydroxy groups may not be
favored (1,3-diaxial interaction), leading to a lower conversion.

3776
In summary, we have demonstrated the feasibility of selective monotosylation of internal diols using
catalytic amounts of n-Bu2SnO (ca. 2 mol%). Additionally, we have demonstrated that, for efficient
catalysis in the case of cyclic substrates, an α-chelatable moiety cis to the hydroxy group should
be present. The use of catalytic n-Bu2SnO to effect sulfonylation affords dramatic rate enhancement
relative to the uncatalyzed version, and minimal waste. This protocol obviates the need for extensive
chromatographic removal of stoichiometric lipophilic tin waste.
Acknowledgements
The authors thank Professors Leo Paquette, Peter Wipf, William Roush and Marvin Miller for helpful
discussions.
References
1. Shanzer, A. Tetrahedron Lett. 1980, 21, 221.
2. (a) David, S.; Hanessian, S. Tetrahedron 1985, 41, 643. (b) Grindley, T. B. Adv. Carbohydr. Chem. Biochem. 1998, 53, 17.
3. O’Donnell, C. J.; Burke, S. D. J. Org. Chem. 1998, 63, 8614.
4. Boons, G.-J.; Castle, G. H.; Clase, J. A.; Grice, P.; Ley, S. V.; Pinel, C. Synlett 1993, 913.
5. (a) Leigh, D. A.; Martin, R. P.; Smart, J. P.; Truscello, A. M. J. Chem. Soc., Chem. Commun. 1994, 1373. (b) Reginato, G.;
Ricci, A.; Roelens, S.; Scapecchi, S. J. Org. Chem. 1990, 55, 5132.
6. (a) Martinelli, M. J.; Nayyar, N. K.; Moher, E. D.; Dhokte, U. P.; Pawlak, J. M.; Vaidyanathan, R. Org. Lett. 1999, 1,
447. (b) A recent paper describes the selective monobenzoylation of diols using catalytic Me2SnCl2: Maki, T.; Iwasaki, F.;
Matsumura, Y. Tetrahedron Lett. 1998, 39, 5601.
7. The n-Bu2SnO-catalyzed tosylations are slower in dioxane than in CH2Cl2.
8. Tsuda, Y.; Nishimura, M.; Kobayashi, T.; Sato, Y.; Kanemitsu, K. Chem. Pharm. Bull. 1991, 39, 2883.
9. Typical experimental procedure: To a solution of the diol (2.5 mmol) in CH2Cl2 (5 mL) were added n-Bu2SnO (0.02
equiv.), TsCl (1.05 equiv.) and Et3N (1.1 equiv.). The reaction mixture was stirred at room temperature until TLC indicated
disappearance of starting material. The mixture was filtered, and the filtrate was concentrated.