Organocatalytic asymmetric Povarov reactions with 2- and 3-vinylindoles

Abstract

The asymmetric Povarov reaction of N-arylimines with 2- and 3-vinylindoles has been developed using a chiral phosphoric acid ((S)-TRIP) as catalyst. The peculiar reactivity of vinylindoles allowed also the disclosure of a Povarov Friedel-Crafts sequence, and the trapping of the reaction intermediate with nucleophilic species, thus providing a versatile platform for the preparation of highly enantioenriched indole derivatives.

An Atropisomerically Enforced Phosphoric Acid for Organocatalytic Asymmetric Reactions

“…Catalyst 4b is not C 2 ‐symmetric; one methyl group points inwards, the second one outwards. Based on our experience in phosphoric acid catalysis and considering these structural features, we initially selected two known asymmetric transformations wherein catalysts 1 and 2 show contrasting behaviors, and which we thought useful to compare the catalytic performances of 4a – c with these phosphoric acid catalysts. We also included the “non‐frozen” 1‐naphthyl‐substituted catalyst 3 for this comparison.…”

“…We first studied the Povarov reaction between the N ‐4‐methoxyphenyl aldimine 7 and 2‐vinylindole 8 (Table ). [19a] In this reaction, the highly hindered catalyst 1 affords very good enantioselectivity (entry 1), whereas the 9‐anthracenyl derivative 2 , bearing flat substituents, is less efficient (entry 2). The 1‐naphthyl‐substituted catalyst 3 affords intermediate results (entry 3).…”

“…(2 S ,4 S )‐4‐(1 H ‐Indol‐2‐yl)‐6‐methoxy‐2‐phenyl‐1,2,3,4‐tetrahydroquinoline (9): [19a] To a flame‐dried Schlenk tube equipped with a magnetic stirring bar, 3 Å spherical‐shaped molecular sieves (ca. 70 mg) were added under a N 2 atmosphere.…”

Catalytic Asymmetric Inverse‐Electron‐Demand (IED) [4+2] Cycloaddition of Salicylaldimines: Preparation of Optically Active 4‐Aminobenzopyran Derivatives

“…[6] In this context, the development of new catalytic asymmetric methods for the preparation of the benzopyran structure attracted our interest. Following our recent report on the asymmetric Povarov [7] reaction of N-arylimines with 2-and 3-vinylindoles using chiral BINOL-derived phosphoric acids [8,9] as catalyst, we decided to examine the feasibility of an enantioselective inverse-electron-demand (IED) [4 + 2] cycloaddition of o-hydroxybenzaldimines 1 with electron-rich alkenes. In particular, besides the evident synthetic utility of this reaction, we were intrigued by the possible competing pathways expected in the reactions of these imines with electron-rich dienophiles, leading to two distinct products.…”

Organocatalysts for enantioselective synthesis of fine chemicals: definitions, trends and developments

“…Noteworthy examples are Povarov reactions, O-alkylations, Pictet-Spengler reactions or benzidine rearrangement [73][74][75][76]. Chiral BA have shown particularly successful performances in the acetalisation reaction [77][78][79].…”