Selective phosphorylation of diols with a Lewis acid catalyst

We report a method for the Lewis acid catalyzed phosphorylation of diols with pyrophosphates. Titanium alkoxides were found to be effective catalysts in the selective mono-phosphorylation for a range of diols. Diols of varying chain lengths and substituents were screened, to study the factors that influence mono- versus di-phosphorylation. It was discovered that 2-alkyl-2-amino-1,3-propanediols can be selectively mono-phosphorylated in up to 97% isolated yield. This structural core is mono-phosphorylated in numerous immunomodulating compounds including the FDA-approved drug, FTY720.67