title: The Activation of Carboxylic Acids via Self-Assembly Asymmetric Organocatalysis: A Combined Experimental and Computational Investigation.
abstract: The heterodimerizing self-assembly between a phosphoric acid catalyst and a carboxylic acid has recently been established as a new activation mode in Brønsted acid catalysis. In this article, we present a comprehensive mechanistic investigation on this activation principle, which eventually led to its elucidation. Detailed studies are reported, including computational investigations on the supramolecular heterodimer, kinetic studies on the catalytic cycle, and a thorough analysis of transition states by DFT calculations for the rationalization of the catalyst structure-selectivity relationship. On the basis of these investigations, we developed a kinetic resolution of racemic epoxides, which proceeds with high selectivity (up to s = 93), giving the unreacted epoxides and the corresponding protected 1,2-diols in high enantiopurity. Moreover, this approach could be advanced to an unprecedented stereodivergent resolution of racemic α-chiral carboxylic acids, thus providing access to a variety of enantiopure nonsteroidal anti-inflammatory drugs and to α-amino acid derivatives.
authors: Max-Planck-Institut für Kohlenforschung , Kaiser-Wilhelm Platz 1, Mülheim an der Ruhr 45470, Germany.
authors: Mattia Riccardo
authors: MR
authors: Monaco
authors: Max-Planck-Institut für Kohlenforschung , Kaiser-Wilhelm Platz 1, Mülheim an der Ruhr 45470, Germany.
authors: Daniele
authors: D
authors: Fazzi
authors: Max-Planck-Institut für Kohlenforschung , Kaiser-Wilhelm Platz 1, Mülheim an der Ruhr 45470, Germany.
authors: Nobuya
authors: N
authors: Tsuji
authors: Max-Planck-Institut für Kohlenforschung , Kaiser-Wilhelm Platz 1, Mülheim an der Ruhr 45470, Germany.
authors: Markus
authors: M
authors: Leutzsch
authors: Max-Planck-Institut für Kohlenforschung , Kaiser-Wilhelm Platz 1, Mülheim an der Ruhr 45470, Germany.
authors: Saihu
authors: S
authors: Liao
authors: Max-Planck-Institut für Kohlenforschung , Kaiser-Wilhelm Platz 1, Mülheim an der Ruhr 45470, Germany.
authors: Walter
authors: W
authors: Thiel
authors: Max-Planck-Institut für Kohlenforschung , Kaiser-Wilhelm Platz 1, Mülheim an der Ruhr 45470, Germany.
authors: Benjamin
authors: B
authors: List