De Novo Design and Asymmetric Synthesis of a <i>C</i>-1/2 Benzodioxin Fused Glycoside Analogue of Lincomycin

An <i>in silico</i> designed benzodioxin fused analogue of a des-(1-hydroxyethyl)-lincomycin analogue was synthesized in a <i>de novo</i> asymmetric fashion from an achiral acylfuran, a 4-(<i>n</i>-Pr)-<i>N</i>-methyl-proline, and catechol. The synthesis of the 6-amino-galactose portion of the lincomycin analogue necessitated the development of a novel stereospecific tandem Pd-glycosylation/1,4-addition reaction between catechol and an <i>N</i>-Cbz-protected 6-amino-pyranone with a Pd-π-allyl leaving group at the <i>C</i>-1 position. The desired <i>galacto</i>-stereochemistry was installed by a subsequent stereoselective ketone reduction, alcohol elimination, and diastereoselective dihydroxylation of the <i>C</i>-3/4 alkene.