Second-generation synthesis of protected phosphonothiodifluoromethylene analogues of nucleoside-3′-phosphates

A practical, eight-step synthesis of the key intermediate 14 in 19% overall yield from α-d-xylose is described. The preparation can be carried out on multi-gram scale and involves the use of the organomagnesium reagent 2d. The capability of derivative 14 to be transformed into the title compounds is examplified by the preparation of 15. Additionally, X-ray crystallography of intermediate 12 provided the first structural data on difluorophosphonothioates.