Organocatalytic Enantioselective Friedel−Crafts Reaction of Pyrrole Derivatives with Imines

Abstract

A highly enantioselective Friedel-Crafts reaction of pyrrole derivatives with N-acyl imines catalyzed by chiral phosphoric acids was developed. The reactions produced the pyrrole derivatives in high yields and enantioselectivity.

The mechanism investigation of chiral phosphoric acid-catalyzed Friedel–Crafts reactions – How the chiral phosphoric acid regains the proton

“…Particularly we would like to discover if the proton comes from the carbon or the nitrogen atom of the pyrrole ring (refer to a and b in Scheme 1). To answer this question, we studied the Friedel-Crafts reaction with pyrrole and imine [13] (as shown in Scheme 2), we tried to explain this question using theoretical methods.…”

Enantioselective Synthesis of Amines by Chiral Brønsted Acid Catalysts

“…The enantioselective F-C reactions catalyzed by chiral phosphoric acids were further applied to such electron-rich aromatic compounds as pyrroles (Scheme 3.19a and b) [45,46] and 4,7-dihydroindoles (Scheme 3.19c) [47]. The reaction of 4,7-dihydroindoles yielded 2-substituted indole derivatives following oxidation of the F-C products.…”

Selective Synthesis of β‐Alkylpyrroles

“…However, as described in the previous paragraph, the preferential a-nucleophilicity of pyrroles actually makes the b-alkylation considerably difficult. In fact, a vast amount of research has thus far been devoted to exclusive or selective aalkylation of pyrroles, in which various organic molecules such as alkenes, [7] alcohols, [8] allylic acetates, [9] ketones, [10] imines, [11] epoxides, [12] aziridines [12] and diazo compounds [13] have been the alkylating agents of choices. Under such situation, how do you alkylate pyrroles at the b-position regioselectively?…”