Recent advances in the asymmetric synthesis of pharmacology-relevant nitrogen heterocycles<i>via</i>stereoselective aza-Michael reactions

Vinogradov, M. G.; Turova, O. V.; Zlotin, Sergei G.

doi:10.1039/c8ob03034k

Cited by 128 publications

(54 citation statements)

References 266 publications

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“…The terms aza‐Michael reaction and oxa‐Michael reaction have been used to refer to the 1,4‐addition of nitrogen and oxygen nucleophiles, respectively. The aza‐Michael reaction (aza‐MR) is one of the most important synthetic tools for the formation of a C─N bond …”

Section: Introductionmentioning

confidence: 99%

Synthesis of heterocyclic compounds via Michael and Hantzsch reactions

Abdella

Abdelmoniem

Abdelhamid

et al. 2020

Journal of Heterocyclic Chem

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Heterocycles represent the largest diversity of organic compounds with signifcant chemical, biomedical, and industrial applications. They exist in numerous natural products, dyes, and as scaffolds in diverse drugs and related pharmaceutically active substances. Substantial attention has been paid to develop various elegant methods to synthesize heterocycles. Among different strategies, Michael and Hantzsch reactions are considered as effective approaches for construction of heterocycles and their corresponding fused derivatives. This review covers this area especially in the last 10 years. The heterocyclic systems reported in this review are classified according to the kind of the heterocyclic systems.

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Section: Introductionmentioning

confidence: 99%

Synthesis of heterocyclic compounds via Michael and Hantzsch reactions

Abdella

Abdelmoniem

Abdelhamid

et al. 2020

Journal of Heterocyclic Chem

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“…Oxa-, [3][4][5] aza-, [6][7][8] thia-, [9][10][11] and phospha- [12] Michael addition reactions are the conceptual extension to heteroatom-centered anions. Utility of the Michael additions for the constructiono f CÀCb ond employing carbon nucleophiles are very well developed.…”

Section: Introductionmentioning

confidence: 99%

KOtBu‐Catalyzed Michael Addition Reactions Under Mild and Solvent‐Free Conditions

Thiyagarajan

Krishnakumar

Gunanathan

2020

Chemistry An Asian Journal

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Designed transition metal complexes predominantly catalyze Michael addition reactions. Inorganic and organic base‐catalyzed Michael addition reactions have been reported. However, known base‐catalyzed reactions suffer from the requirement of solvents, additives, high pressure and also side‐reactions. Herein, we demonstrate a mild and environmentally friendly strategy of readily available KOtBu‐catalyzed Michael addition reactions. This simple inorganic base efficiently catalyzes the Michael addition of underexplored acrylonitriles, esters and amides with (oxa‐, aza‐, and thia‐) heteroatom nucleophiles. This catalytic process proceeds under solvent‐free conditions and at room temperature. Notably, this protocol offers an easy operational procedure, broad substrate scope with excellent selectivity, reaction scalability and excellent TON (>9900). Preliminary mechanistic studies revealed that the reaction follows an ionic mechanism. Formal synthesis of promazine is demonstrated using this catalytic protocol.

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“…Although the development of heterocycle‐related field merges with that of chemistry, there are continuous improvements in their synthesis . This is because heterocycle derivatives have displayed broad spectrum applications in medicine, agriculture, industry, and chemistry . In this context, selenium‐containing heterocycles, even though not present in natural products, have been widely used in material science, as intermediaries in organic synthesis, and also searched for different biological activities .…”

Section: Introductionmentioning

confidence: 99%

Iron‐Mediated Cyclization of 1,3‐Diynyl Propargyl Aryl Ethers with Dibutyl Diselenide: Synthesis of Selenophene‐Fused Chromenes

2020

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The synthesis of selenophene‐fused chromene derivatives starting from 1,3‐diynyl propargyl aryl ethers is reported herein. The method is based on carbon‐carbon, carbon‐selenium, selenium‐carbon and carbon‐selenium bonds formation in a one‐pot protocol, using iron(III) chloride and dibutyl diselenide as promoters. The same reaction conditions were applied to propargyl anilines leading to the formation of 1‐(butylselanyl)‐selenophene quinolines. The results showed that the dilution and temperature of substrate addition had a crucial influence in the products obtained. When the substrates were added at room temperature, in the absence of a solvent, a mixture of products was obtained, whereas the slowly addition (15 min) of starting materials, as a dichloromethane solution, at 0 °C led to the product formation in good yields. The mechanistic study indicates that the cooperative action between iron(III) chloride and dibutyl diselenide was essential to promote the cyclization, whereas separately none of them was effective in promoting the cyclization. We proved the synthetic utility of heterocycles obtained in the Suzuki cross coupling reaction, giving the corresponding cross‐coupled products in good yields. In addition, the organoselenium moiety was removed from the structures of products by using n‐butyllithium.

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Recent advances in the asymmetric synthesis of pharmacology-relevant nitrogen heterocyclesviastereoselective aza-Michael reactions

Abstract: In this review, recent applications of a stereoselective aza-Michael reaction for asymmetric synthesis of naturally occurring N-containing heterocyclic scaffolds and their usefulness to pharmacology are summarized.

Cited by 128 publications

References 266 publications

Synthesis of heterocyclic compounds via Michael and Hantzsch reactions

Synthesis of heterocyclic compounds via Michael and Hantzsch reactions

KOtBu‐Catalyzed Michael Addition Reactions Under Mild and Solvent‐Free Conditions

Iron‐Mediated Cyclization of 1,3‐Diynyl Propargyl Aryl Ethers with Dibutyl Diselenide: Synthesis of Selenophene‐Fused Chromenes

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