Organocatalytic Strategies for the Development of the Enantioselective Inverse‐electron‐demand Hetero‐Diels‐Alder Reaction

Abstract

Cycloaddition reactions, in particular Diels-Alder reactions, have attracted a lot of attention from organic chemists since they represent one of the most powerful methodologies for the construction of carbon-carbon bonds. In particular, inverse-electron-demand hetero-Diels-Alder reactions have been an important breakthrough for the synthesis of heterocyclic compounds. Among all their variants, the organocatalytic enantioselective version has been widely explored since the asymmetric construction of diversely functionalized scaffolds under reaction conditions encompassed within the green chemistry field is of great interest. In this review, a profound revision on the latest advances on the organocatalytic asymmetric inverse-electron demand hetero-Diels-Alder reaction is shown.

Diels–Alder Cycloaddition Reactions in Sustainable Media

“…The intramolecular Povarov reaction of 2-aminoarylaldehydes bearing a tethered alkyne moiety with heterocyclic amines catalyzed by Amberlyst-15 in PEG-200 has been described [54]. This metal-free green protocol allowed the synthesis of [1,6]naphthyridine-fused heterocycles 33 and 35 in good yields (60-81%) starting from 2-(N-Scheme 5. Multicomponent reaction of β-ketosulfones, formaldehyde and styrenes in a bio-based binary mixture of GAAS and meglumine.…”

“…The intramolecular Povarov reaction of 2-aminoarylaldehydes bearing a tethered alkyne moiety with heterocyclic amines catalyzed by Amberlyst-15 in PEG-200 has been described [54]. This metal-free green protocol allowed the synthesis of [1,6] The intramolecular Povarov reaction of 2-aminoarylaldehydes bearing a tethered alkyne moiety with heterocyclic amines catalyzed by Amberlyst-15 in PEG-200 has been described [54]. This metal-free green protocol allowed the synthesis of [1,6]-naphthyridinefused heterocycles 33 and 35 in good yields (60-81%) starting from 2-(N-propargylamino)-arylaldehydes 31 and 3-aminocoumarins 32 or 3-methyl-1-aryl-1H-pyrazol-5-amines 34, respectively (Scheme 7).…”

“…This metal-free green protocol allowed the synthesis of [1,6] The intramolecular Povarov reaction of 2-aminoarylaldehydes bearing a tethered alkyne moiety with heterocyclic amines catalyzed by Amberlyst-15 in PEG-200 has been described [54]. This metal-free green protocol allowed the synthesis of [1,6]-naphthyridinefused heterocycles 33 and 35 in good yields (60-81%) starting from 2-(N-propargylamino)-arylaldehydes 31 and 3-aminocoumarins 32 or 3-methyl-1-aryl-1H-pyrazol-5-amines 34, respectively (Scheme 7). The synthesis of these heterocyclic systems involves the initial formation of imine intermediate 36, followed by an Amberlyst-15 promoted intramolecular [4 + 2] hetero Diels-Alder reaction as the key step.…”

“…The Diels-Alder reaction, a concerted [4 + 2] cycloaddition of a conjugated diene and a dienophile, is a powerful tool for the regio-and stereoselective construction of six-membered rings [1][2][3][4][5][6]. In its original version, two new C-C bonds are created in the Diels-Alder reaction and six-membered carbocyclic systems are obtained.…”

Bifunctional thiourea-catalyzed asymmetric [3 + 2] annulation reactions of 2-isothiocyanato-1-indanones with barbiturate-based olefins

“…Therefore, this structural motif has attracted great attention of researchers in the field of synthetic organic chemistry and pharmaceutical chemistry all over the world. In the previous few decades, a large number of strategies emerged to construct heterocyclic compounds with this skeleton or similar ones [6][7][8][9][10], aiming to explore biological activity and medicinal value conveniently and comprehensively. However, as we know, the construction of these compounds is mostly carried out through transition-metal-catalyzed cyclization reactions [11][12][13][14], whereas strategies using bifunctional chiral thiourea catalysts are rarely reported.…”