Efficient access to general α-tertiary amines via water-accelerated organocatalytic multicomponent allylation

Abstract

A tetrasubstituted carbon atom connected by three sp3 or sp2-carbons with single nitrogen, i.e., the α-tertiary amine (ATA) functional group, is an essential structure of diverse naturally occurring alkaloids and pharmaceuticals. The synthetic approach toward ATA structures is intricate, therefore, a straightforward catalytic method has remained a substantial challenge. Here we show an efficient water-accelerated organocatalytic method to directly access ATA incorporating homoallylic amine structures by exploiting readily accessible general ketones as useful starting material. The synergistic action of a hydrophobic Brønsted acid in combination with a squaramide hydrogen-bonding donor under aqueous condition enabled the facile formation of the desired moiety. The developed exceptionally mild but powerful system facilitated a broad substrate scope, and enabled efficient multi-gram scalability.

Accelerating Drug Discovery: Synthesis of Complex Chemotypes via Multicomponent Reactions

“…An α-tertiary amine moiety is an important structural motif that is present in various biologically active natural products and pharmaceuticals. 50 With a specific focus on obtaining αtriphenylmethylamines, a versatile synthetic route was developed utilizing a Brønsted acid-catalyzed (BA) Betti reaction. 51 Since reactive imine species can be formed in situ from their stable precursors, it was reasoned that a benzophenone-derived iminium species (68, Scheme 16) could act as a highly reactive electrophile for poor nucleophiles, such as phenols, and enable 1,2-addition of aryl rings in a formal Betti reaction.…”

Photoredox-Nickel Dual-Catalyzed C-Alkylation of Secondary Nitroalkanes: Access to Sterically Hindered α-Tertiary Amines

“…Curtius rearrangement can also be used but requires potentially dangerous intermediates . Advances in transition metal-catalyzed alkene hydroamination and hydroazidation, alkane C–H amination, decarboxylative azidation, and (most recently) conjugate addition or heteroarylation of α-amino radicals have made progress in the ability to prepare α-tertiary amines (Figure , top) …”

Design, preparation and characterization of Fe3O4@SiO2@ECH@thiocarbazide@Au(i)@chitosan nanoparticles as a catalyst for the synthesis of 3,4-dihydropyrano[3,2-c]chromenes

“…Among them, one-pot multicomponent reactions (MCRs) are powerful tools for the synthesis of complex heterocyclic constructions, based on procedure simplicity, energy saving, cost-effectiveness, atom economy, and green solvent compatibility [20][21][22]. Water compatibility is one notable beneficial aspect of multicomponent reaction due to being safe, eco-friendly, readily available, and inexpensive [23]. It is worth mentioning that some reactants are not well-solved in water application in organic transformation is limited.…”

“…20–22 Water compatibility is one notable beneficial aspect of multicomponent reactions, due to it being safe, eco-friendly, readily available, and inexpensive. 23 It is worth a mention that are still some issues regarding the reactants for water applications and organic transformation is limited. A one-pot three-component reaction is the most common procedure for the synthesis of 3,4-dihydropyrano[3,2- c ]chromenes via the reaction of aldehyde, malononitrile, and cyclohexane-1,3-dione in the presence of an organo-catalyst and a nanocatalyst.…”