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H. Chen, E. Plettner / Tetrahedron Letters 53 (2012) 2059–2062
Acknowledgments
This project was founded by Natural Sciences and Engineering
Research Council of Canada (NSERC) strategic grants STGP35104-
5-2007 and STGP/396484-10, and in part, by Human Frontiers Sci-
ence Project (HFSP) grant RGP0042/2007.
Supplementary data
Supplementary data (experimental procedures and character-
ization data (1H, 13C NMR, IR, MS); molecular optimization using
Gaussian calculations; kinetic data; and the NMR study for dimer-
ization of 2) associated with this article can be found, in the online
Scheme 5. A putative mechanism (SN1-like) of silylation of diol 2 in the absence of
a base and nucleophilic catalyst.
References and notes
involving some degree of covalent bonding has been docu-
mented.19 Therefore, both of the two mechanistic pathways might
exist in our reaction. Namely, both a bimolecular mechanism (SN2-
like) and a SN1-like mechanism are operating during the reaction
process. In the absence of base, the HCl either accumulates in the
solvent or evaporates. In those cases where no base was added,
the HCl caused the 1° silyl ether to back-react, but the 2° allylic si-
lyl ether withstood the HCl and accumulated.
In conclusion, the selective silylation of 2 and 5 proceeds with
high selectivity for substrates in which the secondary allylic and
saturated primary alcohols are sterically different. There are two
potential sites for silylation, the primary –CH2OH and secondary
alcohol giving products 3/6 and 4/7, respectively. Under various
conditions, both sites are observed to be silylated, and in the ab-
sence of base or catalyst, only the secondary site is silylated. In
the presence of in situ generated HCl, the primary silyl product is
unstable, leaving only the secondary one as an observed product.
Our proposed mechanism starts with the nucleophilic attack of
alcohol with TBDMSCl to form a bimolecular transition sate, fol-
lowed by the repulsion of Clꢀ and deprotonation. In the absence
of base, HCl forms, and this causes the desilylation of the 1° silyl
ether. The 2° allylic silyl ether forms more slowly, but is more sta-
ble toward the HCl formed in the reaction. Therefore, in the pres-
ence of base the kinetic (1°) product predominates whereas in
the absence of base the thermodynamic (2° allylic) product
predominates.
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