Desymmetrization of Diols by Phosphorylation with a Titanium-BINOLate Catalyst

The desymmetrization of ten prochiral diols by phosphoryl transfer with a titanium-BINOLate complex is discussed. The phosphorylation of nine 1,3-propane diols is achieved in yields of 50-98%. Enantiomeric ratios as high as 92:8 are achieved with diols containing a quaternary C-2 center incorporating a protected amine. The chiral ligand, base, solvent, and stoichiometry are evaluated along with a nonlinear effect study to support an active catalyst species that is oligomeric in chiral ligand. The use of pyrophosphates as the phosphorylating agent in the desymmetrization facilitates a user-friendly method for enantioselective phosphorylation with desirable protecting groups (benzyl, o-nitrobenzyl) on the phosphate product.