Glycosyl ortho‐Methoxybenzoates: Catalytically Activated Glycosyl Donors with an Easily Removable and Recyclable Leaving Group

Abstract

We describe the β‐ortho‐methoxybenzoate as a shelf stable and practical C‐1 nucleofuge for catalytic chemical glycosylation in which the benzoic acid by‐product can be easily removed, reisolated, and potentially recycled after the glycosylation reaction. This new type of glycosyl donor can be efficiently activated by a range of promoters, including Bi(OTf)3, Fe(OTf)3, TMSOTf (TMS = trimethylsilyl), and triflic acid, with low (<10 mol‐%) catalyst loadings. The donor shows higher reactivity than analogous benzoate, p‐methoxybenzoate and p‐cyano‐o‐methoxybenzoate donors. In glycosylation reactions with o‐methoxybenzoate donors, the yields of disaccharide products were good to excellent for various glycosyl acceptors, including a carbohydrate‐based secondary alcohol. Furthermore, β‐selective mannosylation was achieved with a Crich‐type donor at 0 °C to ambient temperature, without donor preactivation. The donor was also used for the first step of a one‐pot two‐step glycosylation to obtain a trisaccharide; the second coupling involved activation of a thioglycoside with NIS/TMSOTf (NIS = N‐iodosuccinimide). We believe that this offers a good alternative to current protocols.