Methodology development and physical organic chemistry: a powerful combination for the advancement of glycochemistry.

This Perspective outlines work in the Crich group on the diastereoselective synthesis of the so-called difficult classes of glycosidic bond: the 2-deoxy-β-glycopyranosides, the β-mannopyranosides, the α-sialosides, the α-glucopyranosides, and the β-arabinofuranosides with an emphasis on the critical interplay between mechanism and methodology development.