CF₂H, a Hydrogen Bond Donor

The CF₂H group, a potential surrogate for the OH group, can act as an unusual hydrogen bond donor, as confirmed by crystallographic, spectroscopic, and computational methods. Here, we demonstrate the bioisosterism of the OH and CF₂H groups and the important roles of CF₂-H···O hydrogen bonds in influencing intermolecular interactions and conformational preferences. Experimental evidence, corroborated by theory, reveals the distinctive nature of CF₂H hydrogen bonding interactions relative to their normal OH hydrogen bonding counterparts.