An enantioselective multi-component synthesis of 1,2,5,6-tetrahydropyridines (THPs) has been developed through a one-pot domino-process. This transformation proceeds through proline-catalyzed direct Mannich reaction-cyclization of glutaraldehyde with in situ generated imines, followed by site-selective oxidation–reduction sequence under mild conditions. Chiral 1,2,5,6-THPs are obtained in good to high yields (up to 80%) and with the excellent enantioselectivity (up to 98:2 er). The usefulness of this operationally simple method is also shown to synthesize other medicinally important nitrogen-heterocycles.

A quick and highly efficient method for the synthesis of substituted pyrrole-3-methanols from α-iminonitriles and succinaldehyde under microwave irradiation is reported. This one-pot method involves aminocatalyzed direct Mannich reaction-cyclization-dehydrocyanation followed by NaBH4 reduction sequence in good yields (up to 75%). Further applications of this method are demonstrated through the rapid synthesis of polycyclic heterocycles such as pyrrolo-dihydrochromene and pyrrolo-dihydroquinoline compounds.

A simple and highly practical one-pot formal [4 + 2] cycloaddition approach for the enantioselective synthesis of N-PMP-1,2-dihydropyridines (DHPs) is described. This chemistry involves an amino-catalytic direct Mannich reaction/cyclization followed by IBX-mediated chemo- and regioselective oxidation sequence between readily available aqueous glutaraldehyde and imines under very mild conditions. A series of N-PMP-1,2-DHPs have been prepared in high yields and excellent enantioselectivity. This method also gives access to both enantiomers of 1,2-DHPs in surplus amount by shifting the catalyst configuration.

Organocatalytic domino reactions involving amine activation of carbonyl compounds have become the latest chemical technology towards the design and development of useful synthetic methods. In this direction, linear dialdehydes such as succinaldehyde, glutaraldehyde, and other homologous compounds have attracted considerable attention as suitable substrates for amine catalyzed transformations. Due to their unique structural features, dialdehydes can easily engage in recreation of cascade/tandem transformations for the synthesis of valuable natural products and drug molecules. In this review article we discuss the current scenario and potential applications of linear dialdehydes as adequate synthetic substrates for amine catalyzed transformations to access biologically important complex scaffolds.

A sustainable method for the direct access to highly substituted 3-formylpyrroles from 1,4-ketoaldehydes and imine via formal [3 + 2] cycloaddition is reported. This reaction involves a one-pot amine catalyzed chemoselective Mannich-cyclization-aerobic oxidation sequence with good to high yields. Further application of the gram scale reaction as well as synthesis of fully substituted 3-formylpyrrole is also shown.

Cycloaddition/annulation reactions remain the most attractive methods for the synthesis of five membered heterocyclic ring systems. Among the three possible strategies for [3 + 2] cycloaddition, this review focuses on 1,3-carbon donor–acceptor (C3, D–A) cycloaddition/annulation reactions with imines to synthesize pyrrolidines. The formal [3 + 2] cycloaddition, which includes the in situ 1,3-carbon D–A precursor generation through metal catalysis, Lewis acid catalysis and organocatalysis approaches is highlighted. The scope and limitations of this strategy along with its applications in the synthesis of natural product alkaloids reported during the last decade are outlined.

A new method for one-pot synthesis of 2,3-substituted piperidine from N-PMP aldimine and aqueous glutaraldehyde via formal [4+2] cycloaddition is reported. This reaction involves organocatalytic direct Mannich reaction–reductive cyclization with high yields (up to 90%) and excellent enantioselectivities (up to >99%). The practicability of this method is also shown at a gram scale as well as through the synthesis of functionalized (−)-anabasine.

Amine catalysis, through HOMO-activating enamine and LUMO-activating iminium-ion formation, is receiving increasing attention among other organocatalytic strategies, for the activation of unmodified carbonyl compounds. Particularly, the HOMO-raising activation concept has been applied to the greatest number of asymmetric transformations through enamine, dienamine, and SOMO-activation strategies. Recently, trienamine catalysis, an extension of amine catalysis, has emerged as a powerful tool for synthetic chemists with a novel activation strategy for polyenals/polyenones. In this review article, we discuss the initial developments of trienamine catalysis for highly asymmetric Diels–Alder reactions with different dienophiles and emerging opportunities for other types of cycloadditions and cascade reactions.

A robust method for the synthesis of substituted pyrrole-3-carboxaldehydes from N-PMP aldimines and succinaldehyde is reported. This reaction involves an organocatalytic direct Mannich reaction, and an acid catalyzed cyclization and oxidative aromatization sequence with high yields (up to 82%).

The intramolecular alkyne–azide Huisgen [3+2] cycloaddition reaction as a ‘click-chemistry’ reaction without a metal catalyst has been studied under aerobic conditions. The synthesis of various pyrrolidine–triazole hybrid compounds has also been achieved by using this intramolecular cycloaddition reaction in water with complete 1,5-regioselectivity.((4S,5S)-5-(Azidomethyl)-2,2-dimethyl-1,3-dioxolan-4-yl)methanolC7H13N3O3[α]D25=-69.3 (c 1, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (4S,5S)(4S,5S)-4-(Azidomethyl)-5-ethynyl-2,2-dimethyl-1,3-dioxolaneC8H11N3O2[α]D25=-109.6 (c 1, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (4S,5S)(3bS,6aS)-5,5-Dimethyl-6a,7-dihydro-3bH-[1,3]-dioxolo[4′,5′:3,4]pyrrolo[1,2-c][1,2,3]triazoleC8H11N3O2[α]D25=-64.5 (c 0.75, MeOH)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (3bS,6aS)Methyl 3-((4S,5S)-5-(azidomethyl)-2,2-dimethyl-1,3-dioxolan-4-yl)propionateC10H13N3O4[α]D25=-98.7 (c 0.75, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (4S,5S)(3bS,6aS)-Methyl 5,5-dimethyl-6a,7-dihydro-3bH-[1,3]dioxolo[4′,5′:3,4]pyrrolo[1,2-c][1,2,3]triazole-3-carboxylateC10H13N3O4[α]D25=-86.5 (c 1, MeOH)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (3bS,6aS)(4S,5S)-Methyl 4,5-dihydroxy-5,6-dihydro-4H-pyrrolo[1,2-c][1,2,3]triazole-3-carboxylateC7H9N3O4[α]D25=-38.5 (c 0.5, MeOH)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (4S,5S)

A new method for one-pot synthesis of 2,3-substituted piperidine from N-PMP aldimine and aqueous glutaraldehyde via formal [4+2] cycloaddition is reported. This reaction involves organocatalytic direct Mannich reaction–reductive cyclization with high yields (up to 90%) and excellent enantioselectivities (up to >99%). The practicability of this method is also shown at a gram scale as well as through the synthesis of functionalized (−)-anabasine.

Organocatalytic domino reactions involving amine activation of carbonyl compounds have become the latest chemical technology towards the design and development of useful synthetic methods. In this direction, linear dialdehydes such as succinaldehyde, glutaraldehyde, and other homologous compounds have attracted considerable attention as suitable substrates for amine catalyzed transformations. Due to their unique structural features, dialdehydes can easily engage in recreation of cascade/tandem transformations for the synthesis of valuable natural products and drug molecules. In this review article we discuss the current scenario and potential applications of linear dialdehydes as adequate synthetic substrates for amine catalyzed transformations to access biologically important complex scaffolds.

Amine catalysis, through HOMO-activating enamine and LUMO-activating iminium-ion formation, is receiving increasing attention among other organocatalytic strategies, for the activation of unmodified carbonyl compounds. Particularly, the HOMO-raising activation concept has been applied to the greatest number of asymmetric transformations through enamine, dienamine, and SOMO-activation strategies. Recently, trienamine catalysis, an extension of amine catalysis, has emerged as a powerful tool for synthetic chemists with a novel activation strategy for polyenals/polyenones. In this review article, we discuss the initial developments of trienamine catalysis for highly asymmetric Diels–Alder reactions with different dienophiles and emerging opportunities for other types of cycloadditions and cascade reactions.