Research

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17 pages, 3451 KiB

Open AccessArticle

Investigation of Grignard Reagent as an Advanced Base for Aza-Claisen Rearrangement

by Bo Reum Song, Min Woo Ha, Donghwan Kim, Chanin Park, Keun Woo Lee and Seung-Mann Paek

Molecules 2019, 24(24), 4597; https://doi.org/10.3390/molecules24244597 - 16 Dec 2019

Cited by 3 | Viewed by 2880

Employing iPrMgCl as an advanced base instead of lithium hexamethyldisilazane (LHMDS) resulted in dramatic improvements in aza-Claisen rearrangement. This advance is considered responsible for the increased bulkiness of the alkoxide moiety (including magnesium cation and ligands), followed by a resultant conformational change [...] Read more.

Employing iPrMgCl as an advanced base instead of lithium hexamethyldisilazane (LHMDS) resulted in dramatic improvements in aza-Claisen rearrangement. This advance is considered responsible for the increased bulkiness of the alkoxide moiety (including magnesium cation and ligands), followed by a resultant conformational change of the transition state. To support this hypothesis, various substrates of aza-Claisen rearrangement were prepared and screened. In addition, a molecular dynamic simulation study was performed to investigate and compare the structural stability of reaction intermediates. Full article

(This article belongs to the Special Issue Recent Synthetic Aspects on the Chemistry of Nitro, Nitroso and Amino Compounds II)

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10 pages, 1277 KiB

Open AccessFeature PaperArticle

Organocatalytic Michael Addition to (D)-Mannitol-Derived Enantiopure Nitroalkenes: A Valuable Strategy for the Synthesis of Densely Functionalized Chiral Molecules

by Lucia Caruso, Alessandra Puglisi, Emmerance Gillon and Maurizio Benaglia

Molecules 2019, 24(24), 4588; https://doi.org/10.3390/molecules24244588 - 14 Dec 2019

Cited by 3 | Viewed by 3461

Abstract

Carbohydrates are abundant renewable resources and are a feedstock for green chemistry and sustainable synthesis of the future. Among the hexoses and the pentoses present in biomass, mannitol was selected in the present project as a valuable platform, directly available from the chiral [...] Read more.

Carbohydrates are abundant renewable resources and are a feedstock for green chemistry and sustainable synthesis of the future. Among the hexoses and the pentoses present in biomass, mannitol was selected in the present project as a valuable platform, directly available from the chiral pool, to build highly functionalized molecules. Starting from (R)-2,3-O-cyclohexylidene glyceraldehyde, which is easily prepared in a large scale from D-mannitol, an enantiopure chiral nitro alkene was prepared by reaction with nitromethane, and its reactivity studied. Organocatalytic Michael addition of dimethyl malonate, β-keto esters, and other nucleophiles on the nitro alkene afforded high stereoselectivity and densely functionalized chiral molecules, which were further synthetically developed, leading to five-membered lactones and bicyclic lactams. Preliminary studies showed that the metal-free catalytic reaction on the chiral nitro alkene can be performed under continuous flow conditions, thus enabling the use of (micro)mesofluidic systems for the preparation of enantiomerically pure organic molecules from the chiral pool. Full article

(This article belongs to the Special Issue Recent Synthetic Aspects on the Chemistry of Nitro, Nitroso and Amino Compounds II)

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10 pages, 2385 KiB

Open AccessFeature PaperArticle

A New Valuable Synthesis of Polyfunctionalized Furans Starting from β-Nitroenones and Active Methylene Compounds

by Elena Chiurchiù, Serena Gabrielli, Roberto Ballini and Alessandro Palmieri

Molecules 2019, 24(24), 4575; https://doi.org/10.3390/molecules24244575 - 13 Dec 2019

Cited by 13 | Viewed by 2698

Abstract

Highly functionalized furans are the key scaffolds of many pharmaceuticals and bioactive natural products. Herein, we disclose a new fruitful synthesis of polyfunctionalized furans starting from β-nitroenones and α-functionalized ketones. The protocol involves two steps promoted by solid supported species, and it provides [...] Read more.

Highly functionalized furans are the key scaffolds of many pharmaceuticals and bioactive natural products. Herein, we disclose a new fruitful synthesis of polyfunctionalized furans starting from β-nitroenones and α-functionalized ketones. The protocol involves two steps promoted by solid supported species, and it provides the title targets from satisfactory to very good overall yields and in an excellent diastereomeric ratios. Full article

(This article belongs to the Special Issue Recent Synthetic Aspects on the Chemistry of Nitro, Nitroso and Amino Compounds II)

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19 pages, 3437 KiB

Open AccessFeature PaperArticle

Copper-Mediated Nitrosation: 2-Nitrosophenolato Complexes and Their Use in the Synthesis of Heterocycles

by Alexander J. Nicholls, Andrei S. Batsanov and Ian R. Baxendale

Molecules 2019, 24(22), 4154; https://doi.org/10.3390/molecules24224154 - 16 Nov 2019

Cited by 2 | Viewed by 2862

Abstract

A simple protocol yielding ortho-substituted nitrosophenols from phenols is demonstrated, in the form of copper(II) bis(nitrosophenolato) complexes. The developed methodology was applied to a range of substrates, confirming the role of the copper in both the formation and protection of the [...] Read more.

A simple protocol yielding ortho-substituted nitrosophenols from phenols is demonstrated, in the form of copper(II) bis(nitrosophenolato) complexes. The developed methodology was applied to a range of substrates, confirming the role of the copper in both the formation and protection of the challenging 1, 2-substitution pattern. Using polymer supported thiourea, the Cu could be stripped from the complexes and thus enabled the isolation or identification of the uncoordinated ligands and their decomposition products, in yields generally low in line with the intrinsic high reactivity of 2-nitrosophenols. The product complexes are useful intermediates as demonstrated in revisiting a formal [4 + 2] cycloaddition with dimethylacetylene dicarboxylate to synthesise bicyclic products in variable yields, revealing the product has a novel structure different from those previously reported in the literature. Full article

(This article belongs to the Special Issue Recent Synthetic Aspects on the Chemistry of Nitro, Nitroso and Amino Compounds II)

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13 pages, 2372 KiB

Open AccessArticle

Development of a Telescoped Flow Process for the Safe and Effective Generation of Propargylic Amines

by Kian Donnelly, Huan Zhang and Marcus Baumann

Molecules 2019, 24(20), 3658; https://doi.org/10.3390/molecules24203658 - 10 Oct 2019

Cited by 5 | Viewed by 3152

Abstract

Propargylic amines are important multifunctional building blocks that are frequently exploited in the synthesis of privileged heterocyclic entities. Herein we report on a novel flow process that achieves the safe and effective on-demand synthesis of propargylic amines in a telescoped manner. This process [...] Read more.

Propargylic amines are important multifunctional building blocks that are frequently exploited in the synthesis of privileged heterocyclic entities. Herein we report on a novel flow process that achieves the safe and effective on-demand synthesis of propargylic amines in a telescoped manner. This process minimizes exposure to hazardous azide intermediates and renders a streamlined route into these building blocks. The value of this approach is demonstrated by the rapid generation of a small selection of drug-like thiazolines that result from a high-yielding reaction cascade between propargylic amines with different aryl isothiocyanates. Full article

(This article belongs to the Special Issue Recent Synthetic Aspects on the Chemistry of Nitro, Nitroso and Amino Compounds II)

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10 pages, 927 KiB

Open AccessArticle

Hydro/Deutero Deamination of Arylazo Sulfones under Metal- and (Photo)Catalyst-Free Conditions

by Hawraz I. M. Amin, Carlotta Raviola, Ahmed A. Amin, Barbara Mannucci, Stefano Protti and Maurizio Fagnoni

Molecules 2019, 24(11), 2164; https://doi.org/10.3390/molecules24112164 - 08 Jun 2019

Cited by 24 | Viewed by 4919

Abstract

Hydrodeaminated and monodeuterated aromatics were obtained via a visible-light driven reaction of arylazo sulfones. Deuteration occurs efficiently in deuterated media such as isopropanol-d⁸ or in THF-d⁸/water mixtures and exhibits a high tolerance to the nature and the position of the aromatic substituents. Full article

(This article belongs to the Special Issue Recent Synthetic Aspects on the Chemistry of Nitro, Nitroso and Amino Compounds II)

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11 pages, 1109 KiB

Open AccessArticle

Synthesis, Purification and Characterization of Polymerizable Multifunctional Quaternary Ammonium Compounds

by Ugochukwu C. Okeke, Chad R. Snyder and Stanislav A. Frukhtbeyn

Molecules 2019, 24(8), 1464; https://doi.org/10.3390/molecules24081464 - 13 Apr 2019

Cited by 13 | Viewed by 5795

Abstract

Methacrylate analogs of quaternary ammonium salts functionalized with carboxylic (AMadh1 68.8% yield, AMadh2 53.2% yield) and methoxysilane (AMsil1 94.8% yield, AMsil2 36.0% yield) groups were synthesized via Menschutkin reaction. Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (¹H, ¹³C and [...] Read more.

Methacrylate analogs of quaternary ammonium salts functionalized with carboxylic (AMadh1 68.8% yield, AMadh2 53.2% yield) and methoxysilane (AMsil1 94.8% yield, AMsil2 36.0% yield) groups were synthesized via Menschutkin reaction. Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (¹H, ¹³C and 2D ¹H-¹³C heteronuclear single quantum coherence (HSQC) NMR), mass spectrometry, thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) were utilized to validate structures and characterize thermal properties of the novel multifunctional quaternary ammonium salts synthesized. The potential adhesive, coupling and antimicrobial properties of these multifunctional monomers encourage their further comprehensive evaluation in conventional and experimental copolymers and composites. Full article

(This article belongs to the Special Issue Recent Synthetic Aspects on the Chemistry of Nitro, Nitroso and Amino Compounds II)

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Review

Jump to: Research

31 pages, 9578 KiB

Open AccessReview

The Synthesis and Utility of Metal-Nitrosophenolato Compounds—Highlighting the Baudisch Reaction

by Alexander J. Nicholls, Thomas Barber and Ian R. Baxendale

Molecules 2019, 24(22), 4018; https://doi.org/10.3390/molecules24224018 - 06 Nov 2019

Cited by 7 | Viewed by 5370

Abstract

The syntheses of the title compounds demonstrate a privileged introduction of a nitroso (and a hydroxyl via the Baudisch reaction) group to an aromatic ring. These complexes first appeared in the literature as early as 1939, and a range of applications has subsequently [...] Read more.

The syntheses of the title compounds demonstrate a privileged introduction of a nitroso (and a hydroxyl via the Baudisch reaction) group to an aromatic ring. These complexes first appeared in the literature as early as 1939, and a range of applications has subsequently been published. However, optimisations of the preparative sequences were not considered, and as such, the reactions have seldom been utilised in recent years; indeed, there remains confusion in the literature as to how such complexes form. In this review, we aim to demystify the misunderstanding surrounding these remarkable complexes and consider their renewed application in the 21st century. Full article

(This article belongs to the Special Issue Recent Synthetic Aspects on the Chemistry of Nitro, Nitroso and Amino Compounds II)

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