Synthesis of Enantiomerically Pure 4-Substituted Riboses

An efficient and flexible synthesis of 4-substituted ribose analogues is described. The key step involves the simple addition of a Grignard reagent to a ketone derived from a commercially available ribose. The addition of a range of Grignard reagents proceeded in high yield and with complete stereocontrol, to provide a single enantiomer in every case, the identity of which was confirmed by single-crystal X-ray crystallography. This addition is unaffected by substitution at the 2-position of the starting ribose.