Catalytic Lewis acid phosphorylation with pyrophosphates

We report a method for the Lewis acid catalyzed phosphorylation of alcohols with pyrophosphates. Ti(OtBu)4 was found to be the most effective catalyst in the phosphorylation of both primary and secondary alcohols with tetrabenzylpyrophosphate, providing conversions between 54% and >98% and isolated yields between 50% and 97%. Other pyrophosphates with orthogonal protecting groups were synthesized and screened to validate the generality of the approach. This study will describe how benzyl, methyl, ethyl, allyl, and o-nitrobenzyl pyrophosphates are all effective phosphorylating agents under Lewis acid catalysis.