The role of boronic acids in accelerating condensation reactions of α-effect amines with carbonyls

Abstract

A broad palette of bioconjugation reactions are available for chemical biologists, but an area that still requires investigation is high-rate constant reactions. These are indispensable in certain applications, particularly for in vivo labelling. Appropriately positioned boronic acids accelerate normally sluggish Schiff base condensations of α-effect nucleophiles by five orders of magnitude – providing a new entry to the rare set of reactions that have a rate constant above 100 M⁻¹ s⁻¹ under physiological conditions. I summarize here a number of recent reports, including work from my own group, and outline a mechanistic picture that explains the differing behaviour of seemingly similar substrate classes.