of stoichiometric triethylamine. A dramatic rate acceleration,
Vis a` Vis the stoichiometric version, was also observed.
Dibutyltin oxide has been employed in a catalytic fashion
to effect macrolactonization under neutral conditions,11
presumably as a template for ionic interactions with the
carboxylate and alcohol termini. Similarly, it has been used
as a highly effective, intermolecular transesterification and
esterification catalyst.12 Bu2SnX2 has been utilized in a
catalytic manner to form trimethylsilyl cyanohydrins of
aldehydes and ketones.13 A recent citation describes the use
of catalytic Bu2SnO to accelerate benzoylation of polyols.14
This latter approach was run under conditions with a tunable
microwave heater.15 More recently, dimethyltin dichloride
has been reported as a catalyst for the selective monoben-
zoylation of diols, with added K2CO3 as adjuvant.16 Finally,
application of catalytic Bu2SnO to mediate the addition of
TMS-N3 to nitriles, affording tetrazoles, has been reported.17
During the course of our work on cryptophycin ana-
logues,18 we discovered the catalytic nature of Bu2SnO in
the sulfonylation of 5. Our preliminary experiments are listed
in Table 1. Under the “standard” protocol, diol 5 was
excess Et3N might enhance turnover through competitive tin
binding and neutralization of the newly formed HCl. Thus,
treatment of diol 5 with TsCl and Et3N (1 equiv each) and
catalytic Bu2SnO (2 mol %) led to the results under the
“catalytic” column. It is noteworthy that excellent regio-
selectivity (comparable to the “standard” protocol) is achieved
in this case. More significant is the observed rate acceleration
under these conditions, compared with the “standard”
protocol.
To further exemplify the catalytic effect of dibutyltin oxide
on the tosylation reaction, a rate study was conducted. Diol
11 was chosen as the test substrate. In separate experiments,
1-phenyl-1,2-ethanediol 11 was treated with TsCl (1.05
equiv) and Et3N (1 equiv) in CD2Cl2, in the presence and in
the absence of catalytic Bu2SnO. The conversion to mono-
tosylate 13 was followed by 1H NMR as a function of time
(Figure 1). From this study, it is evident that the Bu2SnO-
catalyzed reaction is at least an order of magnitude faster
than the uncatalyzed version.
Table 1. Comparison of Stoichiometric and Catalytic
Dibutyltin Oxide Tosylations, Relative to Tin-Free Conditions
Figure 1. Rates of monotosylation of diol 11 in the presence and
absence of catalytic Bu2SnO.
converted to the corresponding stannylidene acetal by
treatment with Bu2SnO (1 equiv) in toluene with azeotropic
removal of H2O. After solvent exchange into CH2Cl2, the
stannylidene was treated with TsCl (1 equiv) and Et3N (0.1
equiv) for 18 h to furnish monotosylate 6 as the exclusive
product. Under “tin-free” conditions where the diol was
treated with TsCl (1 equiv) and Et3N (1 equiv) in CH2Cl2,
the byproduct bis-tosylate 7 is usually formed, accompanied
by the starting diol (Scheme 2). The “standard” protocol
employs 0-10 mol % of Et3N presumably since the weak
product-tin complex remains until workup. Whereas the
stannylidene is a tight covalent complex and quite stable,
upon primary alcohol functionalization the complex stability
is significantly diminished. We therefore speculated that
A brief solvent study showed the following trend for
tosylation rate and overall yield: CH2Cl2 > CH3CN > THF
> toluene > MeOH at ambient temperature with catalytic
Bu2SnO. Toluene proved less effective due to an observed
limited solubility, while methanol likely competed for
binding at the tin center. Both of these aspects will manifest
in less efficient reaction progress. Other Sn species were
likewise evaluated in the selective tosylation process and
showed this trend: Bu2SnO g Bu2Sn(OMe)2 > Bu2SnCl2
> Bu2Sn(OAc)2 . Bu3SnCl. We believe this trend is a
reflection of the ability to both form a strong complex with
the glycol and to complete catalyst turnover.
(11) Steliou, K.; Nowosielska, A. S.; Favre, A.; Poupart, M. A.;
Hanessian, S. J. Am. Chem. Soc. 1980, 102, 7579.
Scheme 2
(12) Otera, J.; Dan-oh, N.; Nozaki, H. J. Org. Chem. 1991, 56, 5307.
(13) Whitesell, J. K.; Apodaca, R. Tetrahedron Lett. 1996, 37, 2525.
(14) (a) Morcuende, A.; Valverde, S.; Herrado´n, B. Synlett 1994, 89.
(b) Herrado´n, B.; Morcuende, A.; Valverde, S. Synlett 1995, 455.
(15) Morcuende, A.; Ors, M.; Valverde, S.; Herrado´n, B. J. Org. Chem.
1996, 61, 5264.
(16) Maki, T.; Iwasaki, F.; Matsumura, Y. Tetrahedron Lett. 1998, 39,
5601.
(17) Wittenberger, S. J.; Donner, B. G. J. Org. Chem. 1993, 58, 4139.
(18) Trimurtulu, G.; Ohtani, I.; Patterson, G. M.; Moore, R. E.; Corbett,
T. H.; Valeriote, F. A.; Demchik, L. J. Am. Chem. Soc. 1994, 116, 4729.
448
Org. Lett., Vol. 1, No. 3, 1999