Figure 73: The proposed catalyst/substrate interaction shown in Figure 73 corresponds to the related sulfoxidation catalyzed by chiral phosphoric acid PA 5 (ref 133). Please note that this interaction will be different for PA 43. Figure 105 and surrounding text: The asymmetric reduction was achieved with 1 mol % (S)-PA 25 (ref ). Figure 176 and surrounding text: For the first example of the application of asymmetric counteranion directed catalysis with phosphoric acid salts as catalysts, see ref 29d. Figure 192: The proposed transition state corresponds to the spiroacetalization catalyzed by chiral phosphoric acid (S)-PA 25 (ref 373). Please note that this will be different for PA 43. Figure 196: The correct substrate used is TMSN3. Please note that an alternative mechanism has been proposed (ref 381), as discussed in the surrounding text. Figure 228: The correct structure of 427 is

Addition and Correction to Complete Field Guide to Asymmetric BINOL-Phosphate Derived Brønsted Acid and Metal Catalysis: History and Classification by Mode of Activation; Brønsted Acidity, Hydrogen Bonding, Ion Pairing, and Metal Phosphates

The first enantioselective Friedel–Crafts alkylation of indoles and pyrroles with 3-hydroxy-3-indolyloxindoles to access two novel types of 3,3-diaryloxindoles catalyzed by chiral imidodiphosphoric acids has been reported. A range of quaternary carbon centered 3,3-diaryloxindoles were synthesized in high yield (up to >99%) with excellent enantioselectivity (up to 98% ee) at low catalyst loadings (as low as 0.5 mol%). The Friedel–Crafts reaction between indoles and 3-hydroxy-3-indolyloxindoles is amenable to gram scale syntheses.

Chiral Imidodiphosphoric Acids-Catalyzed Friedel–Crafts Reactions of Indoles/Pyrroles with 3-Hydroxy-indolyloxindoles: Enantioselective Synthesis of 3,3-Diaryloxindoles

Organocatalyzed nucleophilic addition of pyrazoles to 2H-azirines: asymmetric synthesis of 3,3-disubstituted aziridines and kinetic resolution of racemic 2H-azirines

This review aims to bring light upon a very interesting group of compounds, the 1,4-dihydropyridines (1,4-DHPs). These structures are well-known pharmacophores, used for many years to treat cardiovascular diseases because of their activity as calcium channel blockers. In addition, their potential as drugs to treat other affections has been recently exposed. The racemic synthesis of 1,4-DHPs has been well studied, while the asymmetric approaches are mainly based on the use of chiral auxiliaries or chiral resolutions. However, there are scarce examples regarding enantioselective organocatalytic methods. Herein, we will summarize the existing examples in this field of research.

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Organocatalytic Enantioselective Synthesis of 1,4-Dihydropyridines

The purpose of this review is to highlight recent developments in the synthesis of chiral 1,4-dihydropyridines and their fused analogues. 1,4-Dihydropyridines are among the most active calcium antagonists that are used for the treatment of hypertension. Enantiomers of unsymmetrical 1,4-dihydropyridines often show different biological activities and may have even an opposite action profile. Hantzsch synthesis usually produces racemic mixtures of unsymmetrical 1,4-dihydropyridines. Therefore, the development of stereoselective synthesis of 1,4-dihydropyridines is one of the priorities of medicinal chemistry. Over the years, numerous methodologies have been developed for the production of enantiopure 1,4-dihydropyridines, such as stereoselective synthesis using chiral auxiliaries and chiral cyclocondensation partners, chromatographical methods, resolution of diastereomeric 1,4-dihydropyridine salts, enzyme catalysed kinetic resolution, or asymmetrisation of ester groups of 1,4-dihydropyridines. These approaches have been studied in detail and are relatively well established. The catalytic asymmetric approach holds the greatest promise in delivering the most practical and widely applicable methods. Substantial progress has been made toward the development of enantioselective organocatalytic methods for the construction of the chiral dihydropyridines. However, most of them do not provide a convenient way to pharmacologically important 1,4-dihydropyridine-3,5-dicarboxylates. Organocatalytic enantioselective desymmetrisation of prochiral 1,4-dihydropyridine-3,5-dicarbaldehydes also has great promise in the synthesis of pharmacologically important 1,4-dihydropyridine-3,5-dicarboxylates.

Recent Approaches to Chiral 1,4-Dihydropyridines and their Fused Analogues

Penta-substituted 1,4-dihydropyridines were synthesized via catalytic enantioselective cyclization reactions of β,γ-unsaturated α-ketoesters, arylamines and acetylacetone for the first time. H 8 -BINOL-type chiral imidodiphosphoric acid 4c was a suitable catalyst and exhibited high catalytic and stereocontrolling abilities in these enone-type reactions. Under the optimized conditions, these 1,4-dihydropyridines were obtained with excellent enantioselectivities (up to 97% ee). In addition, the typical product 8ba was converted into the corresponding substituted piperidine with high yield (87%) and excellent enantioselectivity (95% ee) in a single-step reduction.

H8-BINOL chiral imidodiphosphoric acids catalyzed cyclization reactions of β,γ-unsaturated α-ketoesters, arylamines and 1,3-dicarbonyl compounds: enantioselective synthesis of 1,4-dihydropyridines

H8‐BINOL Chiral Imidodiphosphoric Acids Catalyzed Cyclization Reactions of β,γ‐Unsaturated α‐Ketoesters, Arylamines and 1,3‐Dicarbonyl Compounds: Enantioselective Synthesis of 1,4‐Dihydropyridines.

Xu Han

Papers

H8-BINOL chiral imidodiphosphoric acids catalyzed cyclization reactions of β,γ-unsaturated α-ketoesters, arylamines and 1,3-dicarbonyl compounds: enantioselective synthesis of 1,4-dihydropyridines

H8‐BINOL Chiral Imidodiphosphoric Acids Catalyzed Cyclization Reactions of β,γ‐Unsaturated α‐Ketoesters, Arylamines and 1,3‐Dicarbonyl Compounds: Enantioselective Synthesis of 1,4‐Dihydropyridines.