Pd-Catalyzed Counter-Steric Site- and Chemoselective Glycosylation: Total Synthesis of Fridamycin A and Himalomycin B

Here, we report a de novo synthetic strategy toward fridamycin-type glycoside natural products. A salient feature of the method is highlighted by the Pd-catalyzed asymmetric hydroalkoxylation of fridamycin A methyl ester with alkoxyallene, which enables site- and chemoselective introduction of 2,3,6-trideoxyglycosysides to various hydroxyl positions in a highly controlled manner. A unique advantage of this method is demonstrated by the total synthesis of himalomycin B and a C₄′-epi derivative of the proposed structure of amicenomycin B.