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

• Published in: European journal of organic chemistry 2012-10, Vol.2012 (30), p.5919-5927
• Main Authors: Lippert, Katharina M., Hof, Kira, Gerbig, Dennis, Ley, David, Hausmann, Heike, Guenther, Sabine, Schreiner, Peter R.
• Format: Article
• Language: English
• Subjects: Catalysis; Catalysts: preparations and properties; Chemistry; Density functional theory computations; Exact sciences and technology; General and physical chemistry; IR spectroscopy; NMR spectroscopy; Organo­catalysis; Spectrum analysis; Theory of reactions, general kinetics. Catalysis. Nomenclature, chemical documentation, computer chemistry; Thiourea derivatives
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201200739

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. The present work reveals that thiourea derivatives bearing a 3,5‐bis(trifluoromethyl)phenyl group interact with Lewis basic sites of carbonyl derivatives through NH and highly polarized ortho‐CH interactions in hydrogen‐bonded complexes. Evidence is provided through a combination of DFT, variable‐temperature IR and NMR spectroscopy, as well as MS (ESI) studies.