Thiourea cooperative activation

Catalytic enantio- and diastereoselective nitroaldol reactions were explored by using designed guanidine-thiourea brfunctional organocatalysts like 15 (Figure 4.4) under mUd and operationally simple biphasic conditions. These catalytic asymmetric reactions have a broad substrate generality with respect to the variety of aldehydes and nitroalkanes [43]. On the basis of studies of structure and catalytic activity relationships, a plausible guanidine-thiourea cooperative mechanism and a transition state of the catalytic reactions are proposed. 

A review has illustrated the importance of atomic-level DFT studies in elucidation of the function of hydrogen bonds in organocatalytic reactions through influence on the mechanism of substrate activation and orientation, and the stabilization of transition states and intermediates. Examples discussed include stereoselective catalysis by bifunctional thioureas, solvent catalysis by fluorinated alcohols in epoxidation by hydrogen peroxide, and intra-molecular cooperative hydrogen bonding in trans-a,a -(dimethyl-l,3-dioxolane-4,5-diyl)bis(diphenyl methanol) (TADDOL) (7)-type catalysts. ... 

Miao, Chen, and coworkers have reported an efficient enantioselective Biginelli reaction catalyzed by a chiral bifunctional primary amine-thiourea derivative 43 with a carbohydrate in the catalyst skeleton and using an external Brpnsted acid in a cooperative way, with t-BuNH TFA as additive (Scheme 9.15) [54]. This protocol renders a wide range of optically active DHPMs 44 in high yields and with good to excellent enantioselectivities (up to 99% ee). 

Brpnsted bases have been explored in cooperative catalysis to deprotonate substrates that subsequently add to metal-activated electrophiles. Regarding the use of these organocatalysts in cooperative catalysis, the combination of quinine and quinine-derived thiourea organocatalysts with Cu(II)-PhBox and Cu(OTf) has been employed in aza-Henry [23] and... 

Interfacially active guanidinium-thiourea bifunctional catalyst 190 catalyzes highly enantioselective nitroaldol reactions in the presence of an external base such as KOH in toluene/water biphasic conditions. Although the retro-nitroaldol reactions generally proceed under basic conditions, addition of KI inhibits the retro-process. A cooperative reaction mode between guanidinium and thiourea moieties is supported by experiments using structural variants of 190. A positive nonlinear effect is observed between the enantiomeric excess of 190 and the product 191. These results support the hypothesis that self-a egation of 190 is necessary for catalysis (Scheme 28.22) (96, 97). Catalyst 190 has been used in the synthesis of chiral tertiary alcohol products obtained in nitroaldol reactions of nitroalkanes and a-ketoesters [98],... 

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