Acid-Assisted Direct Olefin Metathesis of Unprotected Carbohydrates in Water.

ABSTRACT

The ability to use unprotected carbohydrates in olefin metathesis reactions in aqueous media is demonstrated. By using water-soluble, amine-functionalized Hoveyda-Grubbs catalysts under mildly acidic aqueous conditions, the self-metathesis of unprotected alkene-functionalized α-d-manno- and α-d-galactopyranosides could be achieved through minimization of nonproductive chelation and isomerization. Cross-metathesis with allyl alcohol could also be achieved with reasonable selectivity. The presence of small quantities (2.5 vol %) of acetic acid increased the formation of the self-metathesis product while significantly reducing the alkene isomerization process. The catalytic activity was furthermore retained in the presence of large amounts (0.01 mm) of protein, underlining the potential of this carbon-carbon bond-forming reaction under biological conditions. These results demonstrate the potential of directly using unprotected carbohydrate structures in olefin metathesis reactions under mild conditions compatible with biological systems, and thereby enabling their use in, for example, drug discovery and protein derivatization.