Multicomponent reactions (MCRs) undoubtedly correspond to one of the synthetic strategies that best fit the new demands of chemistry for presenting high atom economy and enabling molecular diversity. ...However, many challenges still exist when products possessing stereogenic centres are formed. The field of asymmetric catalytic reactions has achieved significant progress in recent decades; new applications for chiral ligands and catalysts have been demonstrated and new catalysts have been specifically designed for challenging chemical conversions. In this sense, highly efficient approaches for classic multicomponent reactions such as the Ugi reaction and a number of new asymmetric MCRs have been described. In this review we discuss the recent developments that enable catalytic enantioselective MCRs including the proposed mechanistic pathways.
Multicomponent reactions have demonstrated a remarkable impact on the synthesis of complex compounds, with high atom economy. In this review, the last decade contributions to enantioselective MCRs by focusing on catalytic approaches are discussed.
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•Greener methods for the synthesis of bioactive compounds attract great interest.•Multicomponent reactions allow the straightforward synthesis of intricate molecules.•Ultrasonic waves ...in synthesis may result in shorter reaction time and higher yield.•Use of ultrasound in heterogeneous catalysis proved to be a powerful strategy.
Ultrasound is an essential technique to improve organic synthesis from the point of view of green chemistry, as it can promote better yields and selectivities, in addition to shorter reaction times when compared to the conventional methods. Heterogeneous catalysis is another pillar of sustainable chemistry being the recycling and reuse of the catalysts one of its great advantage. In the other hand, multicomponent reactions provide the synthesis of structurally diverse compounds, in a one-pot fashion, without isolation and purification of intermediates. Thus, the combination of these protocols has proved to be a powerful tool to obtain biologically active organic compounds with lower costs, time and energy consumption. Herein, we provide a comprehensive overview of advances on methods of organic synthesis that have been reported over the past ten years with focus on ultrasound-assisted multicomponent reactions under heterogeneous catalysis. In particular, we present pharmacologically important N- and O-heterocyclic compounds, considering their synthetic methods using green solvents, and catalyst recycling.
We report a C(sp3)−C(sp3) cross‐coupling of alkyl bromides and alkyl chlorides with ethers by dual photoredox‐nickel catalysis. The catalytic system comprises of the organic photocatalyst ...1,2,3,5‐tetrakis(carbazol‐9‐yl)‐4,6‐dicyanobenzene (4‐CzIPN) and bench stable nickel (II) acetylacetonate in the presence of visible‐light, providing the coupling products in up to 92% yield. Preliminary mechanistic studies suggest two catalytic cycles, as well as the photogeneration of bromine or chlorine radicals from halide atoms that are present in the structures of the coupling partners. The halide radical mediates the hydrogen atom transfer event, avoiding the need of an additional HAT catalyst.
A solution-phase combinatorial approach based on the Ugi four-component reaction was implemented for the development of new prolyl peptide–peptoid hybrid catalysts. Three different elements of ...diversity were varied during the creation of the set of catalysts: the amine, oxo, and isocyano components. The multicomponent nature of this process enabled the straightforward generation of a series of peptide–peptoid hybrids having the generic sequence Pro-N-R1-Xaa-NHR3, with Xaa being either Gly (R2 = H) or Aib (R2 = gem-Me) and R1 and R3 either alkyl or amino acid substituents. The catalytic behavior of the peptide–peptoid hybrids was assessed in the asymmetric conjugate addition of aldehydes to nitroolefins, where most of the catalysts showed great efficacy and rendered the Michael adducts with good to excellent enantio- and diastereoselectivity. A molecular modeling study was performed for two distinct catalysts aiming to understand their conformational features. The conformational analysis provided important information for understanding the remarkable stereocontrol achieved during the organocatalytic transformation.
The upgrading of biomass‐derived compounds has arisen in recent years as a very promising research field in both academia and industry. In this sense, a lot of new processes and products have been ...developed, often involving levulinic acid as a starting material or intermediate. In the last few years, though, other scaffolds have been receiving growing attention, especially, angelica lactones. Considering these facts and the emergent applications of said molecules, in this review we will discuss their preparation and applications; the use of these frameworks as starting materials in organic synthesis to produce potential bioactive compounds will be covered, as will their use as a foundation to highly regarded compounds such as liquid alkanes with prospective use as fuels and polymers.
A useful platform: Herein, we discuss the preparation and applications of angelica lactones as biomass‐derived platform chemicals. The use of these frameworks as starting materials in organic synthesis to produce potential bioactive compounds will be covered, as will their use as a foundation to highly regarded compounds such as liquid alkanes with prospective use as fuels and polymers.
Reactions involving C(sp3)–H bonds of azaarenes have been widely studied in recent years as they allow direct functionalization of these N-heterocycles without the use of harsh reaction conditions. ...In this work, we describe the C(sp3)–H functionalization of 4-methylquinazolines and 1-benzylisoquinolines, employing α-substituted β-nitrostyrenes catalyzed by inexpensive copper acetate. Under the optimized condition, 21 pyrrolo1,2-cquinazolines, as well as an imidazo1,2-cquinazoline and 4 pyrrolo2,1-aisoquinolines, were obtained in moderate to good yields. Furthermore, the biological activity of the pyrrolo1,2-cquinazolines was evaluated against Plasmodium falciparum, and promising results were obtained.
A simple and efficient metal-free methodology for the regioselective synthesis of 1,4-disubstituted-1,2,3-triazoles has been developed by applying a novel inverse electron-demand-1,3-dipolar ...cycloaddition approach. The practical one-pot metal-free strategy can be accomplished with various alkylidene malononitriles and aromatic azides in the presence of base.
The use of immobilized capillary enzyme reactors (ICERs) for online ligand screening has been adopted as a new technique for high-throughput screening (HTS). In this work, the selected target was the ...enzyme acetylcholinesterase (AChE), and the AChE-ICERs produced were used in a liquid chromatograph–tandem ion-trap mass spectrometer. The activity and kinetic parameters were evaluated by monitoring the choline’s precursor ion (M + H)+ m/z 104.0 and its ion fragment (C2H3OH) – (M + H)+ m/z 60.0. The assay method was validated using the reference AChE inhibitors tacrine and galanthamine. Two new ligands, out of a library of 17 coumarin derivatives, were identified, and the half-maximal inhibitory concentration (IC50), inhibition constant (K i), and the inhibition mechanism were determined. A coumarin derivative with IC50 similar to tacrine was highlighted.
A transition metal- and oxidant-free visible light-photoinduced protocol for direct functionalization of 2-methylquinolines has been developed. This protocol enabled the C–H functionalization of ...substituted 2-methylquinolines with diacetyl or ethyl pyruvate, under environmentally friendly conditions. A mechanistic investigation based on density functional theory (DFT) calculations provided details about the origins of reactivity and selectivity.
In an endeavor to provide an efficient route to natural product hybrids, described herein is an efficient, highly stereoselective, one‐pot process comprising an organocatalytic conjugate addition of ...1,3‐dicarbonyls to α,β‐unsaturated aldehydes followed by an intramolecular isocyanide‐based multicomponent reaction. This approach enables the rapid assembly of complex natural product hybrids including up to four different molecular fragments, such as hydroquinolinone, chromene, piperidine, peptide, lipid, and glycoside moieties. The strategy combines the stereocontrol of organocatalysis with the diversity‐generating character of multicomponent reactions, thus leading to structurally unique peptidomimetics integrating heterocyclic, lipidic, and sugar moieties.
One shot complexity: The combination of an organocatalytic conjugate addition with a stereoselective multicomponent reaction (MCR) enables the one‐pot synthesis of enantiomerically pure natural product hybrids. Such interplay between organocatalysis and MCRs allows the tunable diversification of up to four structural elements, thus facilitating the rapid exploration of a large chemical space.
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