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 inves- tigations 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.
Monaco M R, Fazzi D, Tsui N, Leutzsch M, Liao S, Thiel W, et al. (2016). The Activation of Carboxylic Acids via Self-Assembly Asymmetric Organocatalysis: A Combined Experimental and Computational Investigation. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 138, 14740-14749 [10.1021/jacs.6b09179].
The Activation of Carboxylic Acids via Self-Assembly Asymmetric Organocatalysis: A Combined Experimental and Computational Investigation
Fazzi D;
2016
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 inves- tigations 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
