Catalytic Enantioselective Intramolecular Aza‐Diels–Alder Reactions

Abstract

A readily available chiral Brønsted acid was identified as an efficient catalyst for intramolecular Povarov reactions. Polycyclic amines containing three contiguous stereogenic centers were obtained with excellent stereocontrol in a single step from secondary anilines and aldehydes possessing a pendent dienophile. These transformations constitute the first examples of catalytic enantioselective intramolecular aza-Diels-Alder reactions.

Domino Transformations of Ene/Yne Tethered Salicylaldehyde Derivatives: Pluripotent Platforms for the Construction of High sp3 Content and Privileged Architectures

“…[36] The Seidel group demonstrated the [4+ +2] cycloaddition chemistry of o-allylsalicylaldehyded erivatives as an approach toward the construction of highly enantio-and diastereoselective polycyclic tetrahydrochromanoquinolines (55,56). [37] These scaffolds were generated from secondary amine substrates 53 and 54.A saresult,i ndolines are reacted with o-allylsalicylaldehyde derivatives (45)b yu sing 20 mol %o fachiral catalyst to give the enantiopure scaffolds of type 56 (Scheme 13). In this synthetic design, electron-withdrawing or electron-donating groups,h eteroarenes like furan, and thiophene rings resident on the dienophile component were well tolerated.…”

Enantioselective Organocatalytic Intramolecular Aza‐Diels–Alder Reaction

“…Additional constraints in the transition state of the unimolecular cycloaddition seem to make the chiral catalysts used in intermolecular versions relatively inefficient for the intramolecular Povarov reaction. In this context, Seidel and co‐workers developed a chiral catalyst possessing two Brønsted acid sites that promoted the first enantioselective intramolecular Povarov reaction of azadienes generated in situ from suitable indoline and aldehyde substrates. One year later, the same group disclosed a kinetic resolution through a phosphoric acid catalyzed enantioselective intramolecular Povarov reaction, in which one of the enantiomers of a racemic 2‐substituted indoline underwent faster cycloaddition with the chiral catalysts than the other .…”

Enantioselective Synthesis of Complex Fused Heterocycles through Chiral Phosphoric Acid Catalyzed Intramolecular Inverse‐Electron‐Demand Aza‐Diels–Alder Reactions

“…[7] Mean-while,i n2 015, Seidela nd co-workersp ioneered the asymmetric intramolecular Povarov reactionb yu sing ac hiral catalyst with two Brønsted acid sites,w hich achievede xcellent diastereo-and enantioselectivity if indolines were employed to generate in situ the reactive2 -azadienes [Eq. (1), Scheme 1C]. [8] Subsequently,t he same group reported the chiral phosphorica cid catalyzedk inetic asymmetrici ntramolecular Povarovr eaction of racemic 2-substitutedi ndolines [Eq. (2), Scheme 1C].…”