The pKa of Brønsted acids controls their reactivity with diazo compounds

Abstract

We study the O-alkylation of phosphate groups by alkyl diazo compounds in a range of small molecules and biopolymers. We show that the relatively high pK_a of phosphate in comparison to the other naturally occurring Brønsted acids can be exploited to control alkylation selectivity. We provide a simple protocol for chemical modification of some of the most important instances of phosphates in natural compounds including in small molecule metabolites, nucleic acids, and peptides.