Selective opening of nucleoside derived acetals to form highly functionalized vinyl ethers

[Display omitted] •Ring opening of cyclic acetal on a protected nucleoside gives high selectivity for a C2 vinyl ether.•High yield and selectivity can be obtained using TMSOTf/NEt3 with a range of protected uridines.•This method allows the formation of a vinyl ether without the need for metals. During efforts to employ a Claisen rearrangement in the synthesis of a complex nucleoside, a highly functionalized, protected vinyl ether was required as a key intermediate. The optimal route to this vinyl ether was found to be a remarkably selective ring opening of a cyclic acetal with TMSOTf and NEt3. In this paper we describe factors affecting the selectivity of this vinyl ether synthesis as well as the scope of the reaction for preparation of highly functionalized nucleoside vinyl ethers.