885696-47-9Relevant articles and documents
Organocatalysts Fold to Generate an Active Site Pocket for the Mannich Reaction
Neuvonen, Antti J.,F?ldes, Tamás,Madarász, ádám,Pápai, Imre,Pihko, Petri M.
, p. 3284 - 3294 (2017/06/09)
Catalysts containing urea, thiourea, and tertiary amine groups fold into a three-dimensional organized structure in solution both in the absence as well as in the presence of substrates or substrate analogues, as indicated by solution NMR and computational studies. These foldamer catalysts promote Mannich reactions with both aliphatic and aromatic imines and malonate esters. Hammett plot and secondary kinetic isotope effects provide evidence for the C-C bond forming event as the turnover-limiting step of the Mannich reaction. Computational studies suggest two viable pathways for the C-C bond formation step, differing in the activation modes of the malonate and imine substrates. The results show that the foldamer catalysts may promote C-C bond formation with an aliphatic substrate bearing a cyclohexyl group by enhanced binding of the substrates by dispersion interactions, but these interactions are largely absent with a simpler catalyst. Additional control experiments demonstrate the ability of simple thiourea catalysts to promote competing side reactions with aliphatic substrates, such as reversible covalent binding of the thiourea sulfur to the imine which deactivates the catalyst, and imine to enamine isomerization reactions. In foldamer catalysts, the nucleophilicity of sulfur is reduced, which prevents catalyst deactivation. The results indicate that the improved catalytic performance of foldamer catalysts in Mannich reactions may not be due to cooperative effects of intramolecular hydrogen bonds but simply due to the presence of the folded structure that provides an active site pocket, accommodating the substrate and at the same time impeding undesirable side reactions.
Sequential enantiodivergent organocatalysis: Reversibility in enantioswitching controlled by a conformationally flexible guanidine/bisthiourea organocatalyst
Sohtome, Yoshihiro,Yamaguchi, Takahisa,Tanaka, Shinji,Nagasawa, Kazuo
supporting information, p. 2780 - 2786 (2013/05/09)
Here we describe our studies on solvent-dependent enantiodivergent Mannich-type reactions utilizing conformationally flexible guanidine/bisthiourea organocatalyst (S,S)-1. Our mechanistic investigations revealed that the stereo-determining steps in both t
Cooperative assistance in bifunctional organocatalysis: Enantioselective mannich reactions with aliphatic and aromatic imines
Probst, Nicolas,Madarász, údám,Valkonen, Arto,Pápai, Imre,Rissanen, Kari,Neuvonen, Antti,Pihko, Petri M.
supporting information; experimental part, p. 8495 - 8499 (2012/09/21)
Hold them tight: Guided by X-ray structures, bifunctional thiourea catalysts containing an activating intramolecular hydrogen bond were redesigned. The new catalysts were used to effect a highly enantioselective Mannich reaction between malonates and both aliphatic and aromatic imines (see scheme; Boc=tert-butoxycarbonyl).
