Organocatalytic Enantioselective aza‐Friedel‐Crafts Reactions of Pyrazolinone Ketimines with Hydroxyindoles and Electron‐Rich Phenols

Abstract

A variety of enantioenriched indole derivatives substituted in the benzene ring were synthesised via an organocatalytic asymmetric aza-Friedel-Crafts reaction of pyrazolinone ketimines with hydroxyindoles. This reaction was also applicabled to electron-rich phenols, yielding the desired products in high yields (up to 99%) and excellent stereo-selectivities (91-99% ee). Moreover, this method presents its potential in the synthesis of structurally novel indole-pyrazolinone conjugate derivatives.

Organocatalyzed Enantioselective Decarboxylative Mannich Reaction of β‐Ketoacids with Pyrazolinone Ketimines for the Construction of Chiral β‐Amino Ketone‐Pyrazolinone Derivatives

“…Later, chiral squaramide‐catalyzed asymmetric aza‐Friedel–Crafts/N,O acetalization domino reactions between 2‐naphthols and pyrazolinone ketimines, and asymmetric Mannich reaction of pyrazolones and pyrazolinone ketimines were reported by Enders' group, respectively (Scheme b and 1c). In 2018, Deng's group reported organocatalytic asymmetric aza‐Friedel‐Crafts reaction of pyrazolinone ketimines with hydroxyindoles to access chiral indole‐pyrazolinone derivatives (Scheme d) . Despite this elegant progress, the realization of asymmetric reaction of pyrazolinone ketimines with different diversities of nucleophilic reagents remains highly desirable and an important goal.…”

Pd‐Catalyzed Asymmetric Addition of Arylboronic Acids to Pyrazolinone Ketimines

“…For example, Enders group pioneered squaramide‐catalyzed enantioselective Strecker reaction of pyzazolin‐5‐one derived ketimines with trimethylsilyl cyanide toward chiral pyrazolone α‐aminonitriles [8] . Subsequently, a few organocatalytic or metal‐catalyzed versions of pyzazolin‐5‐one‐derived ketimines with various nucleophiles, such as naphthols, [9] 2,4‐dihydro‐3H‐pyrazol‐3‐one, [10] 1H‐indol‐4‐ols, [11] β‐ketoacids, [12] silyl enol ethers [13] and benzyl but‐3‐ynoates, [14] were reported. Despite these significant advances, asymmetric addition of arylboronic acids as aryl pronucleophiles to pyrazolinone ketimines remains unexplored so far, probably because of the lack of effective asymmetric catalytic system.…”

Direct Asymmetric Arylation of Imines

“…An organocatalytic enantioselective addition reaction between N ‐Boc ketimines of pyrazolinones and hydroxyindoles was developed (Scheme ) . It provided hydroxyindole‐pyrazolinone derivatives in excellent yields (up to 99%) and enantioselectivities (91–99% ee ).…”