Phosphoric Acid Based Heterodimers in Asymmetric Catalysis

Abstract

Chiral phosphoric acid diesters arguably constitute the most exploited class of catalysts in asymmetric Brønsted acid catalysis. Despite being highly investigated for their acidic properties, these compounds display an amphoteric nature, which has instead been considerably overlooked. The potential of this dichotomous polarity has recently been disclosed and applied to the development of novel reaction modes in organocatalysis. In this account, we present our recent advances in this area, focusing on the establishment of heterodimeric interactions toward the nucleophilic activation of carboxylic acids, thiocarboxylic acids and ketones (via their enols) in asymmetric transformations

Asymmetric phosphoric acid–catalyzed four-component Ugi reaction

“…The heightened acidity of chiral phosphoric acids over carboxylic acids is perceived to accelerate the kinetics of the desired reaction so as to outcompete the background reaction. Also, pioneering reports by List and co-workers suggested that the self-assembled heterodimerization between the CPA and the carboxylic acid brings about a dual effect: enhanced acidity of the catalyst and nucleophilicity of the carboxylic acid (35)(36)(37); both of these favor the catalytic enantioselective Ugi-4CR. A myriad of well-established or custom CPAs with well-defined chiral pockets can be readily applied (38)(39)(40)(41), leading to complete stereocontrol in a-addition of the isocyanide to imine.…”

Chiral guanidine catalyzed cyclization reactions of 1,3-enynes for lactone synthesis: switchable H-bond catalysis

“…(10 mol%), in solvent (1.0 mL) at r.t. for 15 h. Entries 1–11: A1 (0.1 mmol) and B1 (0.1 mmol); entries 12–16: C1 (0.1 mmol) and B1 (0.2 mmol). The er and dr were determined by UPC 2 analysis on a chiral stationary phase. Isolated yield.b3 Å MS (20 mg).…”

“…aUnless otherwise noted, all reactions were carried out with G-2 (10 mol%), A (0.1 mmol), and B (0.1 mmol) in toluene (1.0 mL) at −60 °C for 12 h. The er and dr were determined by HPLC/UPC 2 analysis on a chiral stationary phase. Isolated yield.b G-15 (10 mol%).…”

“…1a); notably, chiral phosphoric acids (CPAs) have maintained their prominence in this field. 2 A bifunctional transition state has been achieved in phosphoric acid-catalyzed reactions, such as those involving imines and others, where it demonstrates the capability for simultaneous activation of a nucleophile and an electrophile. To fully harness the potential of H-bond donor catalysis and achieve a comprehensive mechanistic understanding, emphasizing the distinct attributes of these catalyst classes remains a primary focus of ongoing research endeavors.…”

Harnessing Protonated 2,2′-Bipyridinium Salts as Powerful Brønsted Acid Catalysts in Organic Reactions

“…Significant progress has been made for many enantioselective transformations with the aid of chiral Brønsted acids bearing BINOL (1,1′-binaphthyl-2,2′-diol) scaffolds . It is worth noting that the BINOL-derived phosphoric acids have emerged as one of the most widely used organocatalysts, and hundreds of their derivatives have been synthesized and applied in organic synthesis . A salient feature of this phosphoric acid is that it can enhance its acidity and reactivity via providing an additional Lewis-basic coordination site (Figure D).…”