Quantum Mechanical Investigations of Organocatalysis: Mechanisms, Reactivities, and Selectivities

Stabilization of Proline Enamine Carboxylates by Amine Bases

“…This is well illustrated by the versatility and wide range of different transformations that have been developed in the last decade. A number of theoretical [4] and experimental mechanistic studies [5] for these systems are now available. However, to promote specific reactions the application of dual or cooperative catalyst combinations [6] or the use of (co-catalytic) additives is slowly emerging because this often can prove beneficial for tuning both the reactivity and selectivity of existing catalytic systems.…”

“…This principle was outlined by Seebach, Eschenmoser, and co-workers who created enaminocarA C H T U N G T R E N N U N G box-A C H T U N G T R E N N U N G ylA C H T U N G T R E N N U N G ates by the addition of DBU (1,8-diazabicycloA C H T U N G T R E N N U N G [5. 4.0]-undec-7-ene) to oxazolidinones in THF. [12] This idea was recently exploited by Mayr and co-workers for the kinetic proof of neighboring-group participation in proline enaminocarboxylate catalysis in acetonitrile and THF, [13] and by Blackmond, Armstrong, and co-workers for the reversal of enantioselectivity in proline-catalyzed a-amination of aldehydes in dichloromethane.…”

Enantioselective synthesis of 2,3-disubstituted trans-2,3-dihydrobenzofurans using a Brønsted base/thiourea bifunctional catalyst

“…The mechanism of reactions promoted by bifunctional tertiary amine-thiourea catalysts have been studied experimentally and theoretically by a number of groups. 19 Based on these works, it is assumed that the carbonyl of the pro-nucleophile binds to the thiourea, enhancing the acidity of the -proton, and enabling deprotonation by the proximal tertiary amine to give a (Z)-enolate with subsequent stereodetermining C-C bond formation. The pre-transition state assembly for this step may be characterised by the thiourea binding the oxyanion of the enolate, with the ammonium ion hydrogen bonding to the enone (Figure 1, TS1).…”

2.07 The Aldol Reaction: Organocatalysis Approach

“…In addition, these are supported by B3LYP/6-31 G à calculations. [178][179][180][181][182] In the chair transition state model 350a leading to the corresponding aldol (S)-37, hydrogen bonding between the carbonyl group of electrophile and the carboxylic acid of (S)-proline is formed. The favorable electrostatic interaction of +δ NCH--O δÀ also contributes to the lower energy of transition state 350a.…”