First organocatalytic, diastereoselective synthesis of tRNA wobble nucleosides: (<i>R</i>)- and (<i>S</i>)-methoxycarbonylhydroxymethyluridines (mchm⁵Us) and their acid analogues (chm⁵Us)

A diastereoselective organocatalytic synthesis of (<i>R</i>)- and (<i>S</i>)-methoxycarbonylhydroxymethyluridines (mchm⁵Us) and their acid analogues (chm⁵Us) was developed. The method employs organo- and organometallic-catalyzed cyanosilylation of 5-formyluridine to yield diastereomerically enriched TMS-protected cyanohydrins, which are converted <i>via</i> a Pinner reaction to (<i>R</i>)- and (<i>S</i>)-mchm⁵Us, then hydrolyzed to (<i>R</i>)- and (<i>S</i>)-chm⁵Us.