Preparation of both C5' epimers of 5'-C-methyladenosine: reagent control trumps substrate control

Adenosine-derived ketone 5 was subjected to Noyori asymmetric transfer hydrogenation (ATH) using aqueous sodium formate as a stoichiometric reductant. Despite the well-known sensitivity of ATH to stereoelectronic effects from a contiguous stereogenic center, the 5' stereochemistry was overwhelmingly controlled by the chirality of the catalyst. Both the (5'S,4'R) and the (5'R,4'R) diastereomers could be prepared selectively in good yields. An efficient three-step route that provides ketone 5 in 75% overall yield was developed.