Hydrogen‐Bond‐Mediated Asymmetric Catalysis

Abstract

The utilization of hydrogen bonding as an activation force has become a powerful tool in asymmetric organocatalysis. Significant advances have been made in the recent past in this emerging field. Due to space constraints, this Focus Review summarizes only the key aspects with an emphasis on catalysis based on chiral ureas and thioureas, diols, and phosphoric acids. The examples provided neatly demonstrate that chiral ureas and thioureas, diols, and phosphoric acids display effective and unique activation modes of catalysis for a broad spectrum of asymmetric organic transformations, including single-step and multiple-step cascade reactions. These functionalities, which have the ability to afford efficient H-bond activation of electrophiles including C=O, C=N, aziridines, and epoxides, have established their status as "privileged" functional groups in the design of organocatalysts.

Organocatalytic Conjugate Addition in Stereoselective Synthesis

“…Applying this principle to catalysis by using chiral thioureas or phosphoric acids, a different type of electrophiles could be activated toward an asymmetric nucleophilic attack. [16][17][18] Brønsted bases such as tertiary amines are known to activate carbonyl nucleophiles by deprotonation resulting in chiral ion pairs. 19 These two modes of action can be used separately or combined together in a bifunctional activation mode, resulting in extremely well-defined and reactive transition states (Scheme 11.2, eq 3).…”

Novel phenyl(thio)ureas bearing (thio)oxothiazoline group as potential BACE-1 inhibitors: synthesis and biological evaluation

“…These experiments have been performed using BACE-1 (β-secretase) FRET Kit assay, from PanVera Corporation (Madison, WI, USA), according to the described protocol and using a multiwell spectrofluorometer instrument capable of 530-545 nm excitation and 570-590 nm emission wavelengths (Wallac Victor [2][3][4][5][6][7][8] 1420, Perkin Elmer, Turku, Finland). The procedure is as follow: the substrate and enzyme are diluted according to the described protocol into the provided assay buffer (50 mM Tris, pH 7.5, 10% glycerol).…”

“…Aryl(thio)ureas presenting two N-H groups are well recognized in the very active field of non-covalent organocatalysis for their ability to bind ketones, aldehydes and nitro groups through hydrogen bonding [2][3][4][5][6][7][8] . In addition, they are outstanding neutral compounds for the selective complexation of various anions [9][10][11][12][13][14] and they found application in the (enantio) selective extraction of carboxylate anions [15][16][17][18] .…”

Bifunctional primary amine 2-aminobenzimidazole organocatalyst anchored to trans-cyclohexane-1,2-diamine in enantioselective conjugate additions of aldehydes

“…[1][2][3][4][5] These two function-40 alities work in a cooperative manner when they are present in a rigid 1,2-diamine skeleton such as trans-cyclohexane-1,2-diamine. Different hydrogen bonding moieties, such as thiourea 1, can efficiently catalyze the enantioselective conjugate addition of 1,3-dicarbonyl compounds to nitroalkenes.…”