Stereodefined synthesis of 3-difluoromethyl-benzoxaboroles: novel antimicrobials with unlocked H-bonding

Benzoxaboroles, prominent scaffolds in medicinal chemistry, are typically modified on the benzene ring. In contrast, functionalization of the oxaborol ring is less common and often challenging. Indeed, 3-hydroxy-benzoxaboroles are virtually impossible to isolate due to their tautomeric equilibrium with the carbonyl form. In this work, we introduce a novel class of stereodefined 3-difluoromethyl-benzoxaboroles. The replacement of the hydroxy group with -CHF2 preserves stability while promoting bioactivity, owing to the lipophilic H-bond donor properties of the latter.