Discovery and application of asymmetric reaction by multi-functional thioureas

作者：Miyabe Hideto; Takemoto Yoshiji^*

来源：Bulletin of the Chemical Society of Japan, 2008, 81(7): 785-795.

DOI：10.1246/bcsj.81.785

Novel bifunctional organocatalysts, which Possess a thiourea moiety and an amino group, Were designed and synthesized. We discovered that bifunctional thiourea hearing a tertiary arnino group significantly accelerated several nucleophilic addition reactions of active methylene compounds to electron-deficient double bonds. In these reactions, the double hydrogen-bonding activation of electrophiles hearing nitro, imide, and carbamate groups by the thiourea moiety and Simultaneous deprotonation of nucleophiles by the dimethylamino group of bifunctional thiourea proved to play a crucial role for enhancing both reaction rate and enantioselectivity. We have demonstrated the utility of PEG-bound thiourea as a homogeneous catalyst. Although the reaction rate was somewhat decreased with PEG-bound thiourea, mobilization to a PEG support proved to facilitate the recovery and reuse of thiourea catalyst without affecting the chemical yield and enantioselectivity. A newly designed thiourea catalyst provided Sufficient activation of organoboronic acids to facilitate the enantioselective Petasis transformation of quinolines even at low temperatures. A high degree of stereocontrol was achieved in the reaction of various quinolines and organoboronic acids by using it combination of H2O and NaHCO3 as additives.

• 出版日期2008-7-15