Hydrogen‐Bonding Thiourea Organocatalysts: The Privileged 3,5‐Bis(trifluoromethyl)phenyl Group

We present evidence that the privileged use of the 3,5-bis(trifluoromethyl)phenyl group in thiourea organocatalysis is due to the involvement of the ortho-CH bond in the binding event with Lewis-basic sites. We utilized a combination of low-temperature IR spectroscopy, 2D NMR spectroscopy, nano-MS (ESI) investigations, as well as density functional theory computations [M06/6-31+G(d,p), including solvent corrections as well as natural bond orbital and atoms-in-molecules analyses] to support our conclusions that bear implications for catalyst design.