Urea and thiourea-based catalysts

Thioureas (and less often ureas) as organocatalysts were introduced into synthetic practice by Jacobsen and Schreiner. Further development included the design of bifunctional catalysts combining two thiourea subunits or a thiourea group and chiral amines.  

Especially these more effective bifunctional catalysts are capable of formation of numerous strong hydrogen bonds with the substrates of the catalytic reactions. In earlier studies, these strong hydrogen bonds were considered to be a main stereo-regulating factor in the corresponding catalytic reactions. 

However, more recent studies based on the use of the functionals involving diffusion corrections demonstrated that the weak disperse interactions can play an important role in stereoselection even in the presence of numerous and much stronger bonds. 

---

Initial mechanistic analysis of the Strecker reaction catalyzed by a urea-based organocatalyst (Scheme 3.18) revealed that the catalytic activity is provided by the urea functionality of structurally complex catalyst 1. However, further studies revealed a bifunchonal character of urea and thiourea-based catalysts " as well as the possibility of multiple mechanistic pathways in catalysis of nucleophile-electrophile addition reactions. " Simplified but sufficiently effective (thio)urea catalysts 4a and 4b were used in the hydrocyanation reaction (Scheme 3.19) that was subjected to a combined experimental and computational study. °... 

---