Desymmetrization of Diols by Phosphorylation with a Titanium-BINOLate Catalyst
Erik T. Ouellette, Marshall G. Lougee, Andrea R. Bucknam, Paul Endres, John Y. Kim, Emma Lynch, Elizabeth J. Sisko, Bianca R. Sculimbrene
Abstract
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.