Cooperative Cation‐Binding Catalysis as an Efficient Approach for Enantioselective Friedel–Crafts Reaction of Indoles and Pyrrole

Abstract

In this study, we demonstrated the cooperative cation-binding catalysis as an efficient approach for enantioselective Friedel-Crafts reactiono fi ndoles and pyrroles. By using highly accessible chiral oligoethylene glycol (oligoEG) as the cation-binding catalyst and KF as the base,ahighly enantioselective Friedel-Crafts reactiono fi ndoles,4 ,7-dihydroindoles,a nd pyrrole with bench-stable a-amidosulfones as in-situ equivalents of sensitive imines was achieved.T he scope of this new catalytic protocolw as not limited to aromatici mines. Heteroaromatic and aliphatic substrates as well as a-iminoethyl glyoxylate also afforded the desired productsw ith excellent yields and ees. Thee nforced proximity of the catalyst and substrates in ac hiral cage in situ formed by incorporation of the potassium salt enhancedt he reactivity and efficiently transferred the stereochemical information, mimicking the action of enzymes.

In the Pursuit of (Ald)Imine Surrogates for the Direct Asymmetric Synthesis of Non-Proteinogenic α-Amino Acids

“…12 In 2017, the same research group additionally explored the aza-Friedel-Crafts alkylation of amido sulfone 4b with indole and pyrrole nucleophiles (Scheme 3C). 13 In this study, the authors exploited a cooperative cation-binding catalysis modality with the chiral oligoethylene glycol (oligoEG) C5 and KF as the base, generating the reactive -imino ester in situ. The cage, enforced by the catalyst structure around the potassium ion (assembly 9), creates a fine chiral environment for the aza-Friedel-Crafts to proceed with high enantioselectivity (91-98% e.e.…”

Catalytic C3 aza-alkylation of indoles

“…The second example concerns chiral polyethers, such as 21, that promoted aza-Friedel-Crafts alkylation of indoles through a mechanism requiring the presence of a fluoride ion and involving the formation of a sort of chiral cage, similarly to the concept of the active site in enzymes (Scheme 35b). 131 First of all, catalyst 21 needs to be complexed with a unit of KF. Then, -amidosulfones, used as imine surrogates, are coordinated to the chiral complex.…”

Acid-induced intermolecular [3+2] cycloaddition/oxidation to synthesize polysubstituted benzo[f]isoindole-4,9-diones

“…Due to their wide utility as biologically active agents and key intermediates in organic synthesis, pyrrole derivatives have attracted significant attention from organic chemists, and a variety of efficient methods have been developed for their synthesis. Examples include Hantzsch, [13][14][15][16][17][18] Trofimov, [19][20][21][22] Mannich [23][24][25][26] and Clauson-Kaas reactions, [27][28][29][30] Friedel-Crafts, [31][32][33][34] and [3+2] cycloadditions. [35][36][37][38][39] In recent years, metal-free catalysis of various organic transformations has gained more and more attention.…”