Highly Site‐ and Enantioselective N—H Functionalization of N‐Monosubstituted Aniline Derivatives Affording Pyrazolones Bearing a Quaternary Stereocenter

Abstract

Chiral phosphoric acid catalyzed the regio-and enantioselective N-H functionalization of N-alkylaniline with pyrazolones derived ketimines as electrophiles, providing a variety of chiral pyrazolones containing a tetrasubstituted stereocenter bearing a new N,N'-acetal motif in excellent yields and high enantioselectivities. This strategy was featured by low catalyst loading, mild conditions, and high efficiency and selectivity.

Atroposelective Synthesis of 2‐Arylindoles via Chiral Phosphoric Acid‐Catalyzed Direct Amination of Indoles†

“…Indole‐based atropisomers are a very important class of axially chiral compounds, many of them have become the core skeletons such as natural products, active drugs, and chiral catalysts or ligands (Scheme 1a), [ 1‐6 ] and the development of catalytic asymmetric constructions within these frameworks has become an emerging research area. [ 7‐30 ] In comparison to axially chiral biaryl compounds, [ 8 ] introducing a five‐membered pyrrole component decreases the rotation barrier, thereby affecting the stability of the axial chirality configuration and making it difficult to control the enantioselectivity. [ 7,9 ] Therefore, the asymmetric synthesis of axially chiral indole‐based frameworks presents certain challenges.…”

Accessing unnatural α-amino acids with tetrasubstituted stereogenic centersviacatalytic enantioselective reactions of ketimine-type α-iminoesters/α-iminoamides

“…On the other hand, in 2022 Sun, Ding, and co-workers reported N -alkylanilines as nucleophiles during enantioselective addition to pyrazolinone-type ketimines 7b in the presence of CPA organocatalyst 161j′ (Scheme 96C). 155 However, primary amines and dialkylamines are not suitable nucleophiles in this reaction.…”

“…On the other hand, in 2022 Sun, Ding, and coworkers reported N-alkylanilines as nucleophiles during enantioselective addition to pyrazolinone-type ketimines 7b in the presence of CPA organocatalyst 161j 0 (Scheme 96C). 155 However, primary amines and dialkylamines are not suitable nucleophiles in this reaction. In 2020, Nakamura and co-workers reported a reaction system that involved the in situ formation of ketimines derived from acyclic a-ketoesters 196e and 2-aminobenzamides, and the subsequent intramolecular enantioselective addition of amines for constructing cyclic N,N-acetals 223 (Scheme 97).…”

4-Disubstituted Pyrazolin-3-Ones—Novel Class of Fungicides against Phytopathogenic Fungi

“…Recently, C4-disubstituted pyrazolones, primarily spiropyrazolones, have also attracted increasing attention as biologically active compounds [34][35][36]. Due to the wide spectrum of the biological activity of disubstituted pyrazolones, new asymmetric methods for their synthesis are being actively developed [36][37][38][39][40][41]. C4-disubstituted pyrazolones are recognized as valuable antitumor agents [35,[42][43][44][45][46], antimicrobial substances [47], inhibitors of trypanosomal phosphodiesterase B1 [48], RalA inhibitors [49], and miticides [50].…”