Metal-free intermolecular formal cycloadditions enable an orthogonal access to nitrogen heterocycles

Xie, Lan‐Gui; Niyomchon, Supaporn; Mota, Antonio J.; González, Leticia; Maulide, Nuno

doi:10.1038/ncomms10914

Cited by 107 publications

(62 citation statements)

References 59 publications

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“…The C4-S1 bond length [1.7672 (16) Å ] is shorter than the corresponding values observed previously in two analogous polymorphic forms of diethyl 4,4 0 -disulfanediylbis(6-methyl-2-phenylpyrimidine-5-carboxylate), where the C-S distances were in the range 1.786 (2)-1.795 (2) Å (Cunha et al, 2007;Są siadek et al, 2016). The S1-C41 bond length [1.8234 18Å ] is longer than that observed previously in thiopyrimidine compounds (Mao et al, 2014;Są siadek et al, 2016;Xie et al, 2016). The conformation of the molecule is best defined by the dihedral angles between the pyrimidine ring and the planes of the substituents, i.e.…”

Section: Crystal Structure Analysismentioning

confidence: 68%

Synthesis, crystal structure and cytotoxic activity of novel 5-methyl-4-thiopyrimidine derivatives

et al. 2018

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This article presents the synthesis of three new 4-thiopyrimidine derivatives obtained from ethyl 4-methyl-2-phenyl-6-sulfanylpyrimidine-5-carboxylate as the starting material, namely, ethyl 4-[(4-chlorobenzyl)sulfanyl]-6-methyl-2phenylpyrimidine-5-carboxylate, C 21 H 19 ClN 2 O 2 S, (2), {4-[(4-chlorobenzyl)sulfanyl]-6-methyl-2-phenylpyrimidin-5-yl}methanol, C 19 H 17 ClN 2 OS, (3), and 4-[(4-chlorobenzyl)sulfanyl]-5,6-dimethyl-2-phenylpyrimidine, C 19 H 17 ClN 2 S, (4), which vary in the substituent at the 5-position of the pyrimidine ring. The compounds were characterized by 1 H NMR, 13 C NMR, IR and mass spectroscopies, and also elemental analysis. The molecular structures were further studied by single-crystal X-ray diffraction. Compound (2) crystallizes in the space group P1 with one molecule in the asymmetric unit, whereas compounds (3) and (4) crystallize in the space group P2 1 /c with two and one molecule, respectively, in their asymmetric units. The conformation of each molecule is best defined by the dihedral angles formed between the pyrimidine ring and the planes of the two aryl substituents attached at the 2-and 4-positions. The only structural difference between the three compounds is the substituent at the 5-position of the pyrimidine ring, but they present significantly different features in the hydrogenbond interactions. Compound (2) displays a one-dimensional chain formed by hydrogen bonds and the chains are further extended into a two-dimensional network. Molecules of (3) and (4) generate one-dimensional chains formed through intermolecular interactions. The study examines the cytotoxicity of compounds (3) and (4) against Human umbilical vein endothelial cells (HUVEC) and HeLa, K562 and CFPAC cancer cell lines. The presence of the hydroxymethyl and methyl groups in (3) and (4), respectively, offers an interesting new insight into the structures and behaviour of these derivatives. Compound (4) was found to be nontoxic against CFPAC and HUVEC; however, it shows weak activity against the HeLa and K563 cell lines. The presence of a hydroxy group in (3) significantly increases its cytotoxicity towards both, i.e. the cancer (HeLa, K562 and CFPAC) and normal (HUVEC) cell lines.

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Section: Crystal Structure Analysismentioning

confidence: 68%

Synthesis, crystal structure and cytotoxic activity of novel 5-methyl-4-thiopyrimidine derivatives

et al. 2018

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“…The value of sulfur‐substituted compounds coupled with progress in C−C and C–heteroatom bond formation from C−S bonds, renders alkynyl thioethers appealing alternatives to ynamides. Indeed the ketenethionium pathway (Scheme a) from alkynyl thioethers has recently been invoked in proton‐catalyzed reactions with nitriles, and gold‐catalyzed reactions with sulfides…”

Section: Methodsmentioning

confidence: 99%

Alkynyl Thioethers in Gold‐Catalyzed Annulations To Form Oxazoles

2017

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Non‐oxidative, regioselective, and convergent access to densely functionalized oxazoles is realized in a functional‐group tolerant manner using alkynyl thioethers. Sulfur‐terminated alkynes provide access to reactivity previously requiring strong donor‐substituted alkynes such as ynamides. Sulfur does not act in an analogous donor fashion in this gold‐catalyzed reaction, thus leading to complementary regioselective outcomes and addressing the limitations of using ynamides.

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“…This reactivity was exploited by Maulide in 2016 for the synthesis of isoquinolines 139 from ynamides 137 and nitriles 138 through a formal [4+2] cycloaddition process (Scheme ) . In the presence of triflic acid in 1,2‐dichloroethane at 120 °C, a broad range of ynamides 138 were converted into representatives of this important class of nitrogen‐containing heterocycles in good yields.…”

Section: [4+2] Cycloadditions Of Ynamidesmentioning

confidence: 99%

Diels–Alder and Formal Diels–Alder Cycloaddition Reactions of Ynamines and Ynamides

et al. 2017

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Nitrogen‐substituted alkynes such as ynamines and ynamides are competent partners in [4+2] cycloaddition reactions. This microreview aims to discuss in a historical context the main achievements in the work on this class of reactions that leads to valuable nitrogen‐containing heterocycles in a single‐step fashion. In the last section, our own work in the field of inverse‐electron‐demand Diels–Alder reactions between ynamides and pyrimidines is discussed.

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Metal-free intermolecular formal cycloadditions enable an orthogonal access to nitrogen heterocycles

Cited by 107 publications

References 59 publications

Synthesis, crystal structure and cytotoxic activity of novel 5-methyl-4-thiopyrimidine derivatives

Synthesis, crystal structure and cytotoxic activity of novel 5-methyl-4-thiopyrimidine derivatives

Alkynyl Thioethers in Gold‐Catalyzed Annulations To Form Oxazoles

Diels–Alder and Formal Diels–Alder Cycloaddition Reactions of Ynamines and Ynamides

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