Matsuda-Heck Arylation of Glycals for the Stereoselective Synthesis of Aryl C-Glycosides.

The methoxymethyl-protected glycal l-amicetal, synthesized de novo from l-ethyl lactate through tandem ring-closing metathesis-isomerization sequence, undergoes a highly trans-diastereoselective Heck-type coupling reaction with various arene diazonium salts to furnish 2,3-unsaturated aryl C-glycosides in moderate to excellent yields. The products can be further functionalized, e.g., by hydrogenation, epoxidation, or dihydroxylation to furnish 2,3,6-tridesoxy, 2,3-anhydro-6-desoxy, or 6-desoxy aryl C-glycosides, respectively. The method was applied to the synthesis of an α-configured 6-desoxy-gliflozin derivative.