Contributions to the Chemistry of N2O and 1-Alkynyltriazenes

Loïc Nicolas Jeanbourquin
EPFL, 2018
Thèse EPFL

Résumé

This thesis describes the utilization of nitrous oxide N2O as an oxidant in oxidative cou-pling reactions and as a nitrogen atom donor in the synthesis of 1-alkynyltriazene and further reactivity of the latter. An overview of N2O and its reactivity is given in chapter 1. Chapter 2 details attempts and findings made in the use of N2O as an oxidant. In a first part, the optimizations made for the oxidative coupling reaction of sterically demanding Grignard reagents are described. The use of lithium amides resulted in a 1.6-fold improvement of the yields. The use of microwave heating enhanced the reaction, giving access to biaryls with very hindered isopropyl ortho substituents. In a second part, the oxidative coupling of C- and N-nucleophiles mediated by copper is described. The oxidation of organoamidocuprate by N2O gave yields lower than 20%. The results concerning the synthesis and reactivity of 1-alkynyltriazenes are exposed in chapter three, starting with the synthesis of new 1-alkynyltriazene. Aryltriazenes were obtained by using an iodocyclization reaction. The products could be used for further transformation. The cleavage of the triazene moiety by iodine or under acidic condition was successfully made. 1-Alkynyltriazenes were isomerized to 1-allenyltriazenes under basic conditions. These 1-allenyltriazenes were shown to be thermally labile. In presence of zinc, 1-allenyltriazenes rearranged to 1-aminopyrazoles. In certain cases, the based-induced isomerization led directly to the 1,3-dienetriazene. Finally, the gold-catalyzed reaction of 1-alkynyltriazene with imines is shown to selectively form 1,3-diaminopyrazoles in good yield. The reaction is tolerant to a large variety of functional groups on the imine reagent. Dibenzyl-substituted in N3 position pyrazoles were successfully hydrogenated to the amino function yielding 1,3-diaminopyrazoles.

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https://infoscience.epfl.ch/record/253071?ln=fr

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Loïc Nicolas Jeanbourquin
EPFL, 2018
Thèse EPFL

Résumé

Official source

https://infoscience.epfl.ch/record/253071?ln=fr

À propos de ce résultat

Concepts associés (12)

Concepts associés

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Publications associées (3)

Publications associées

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Fluorine in an heteroaromatic context

Thierry Rausis

The organometallic approach to the functionalization of arenes and heteroarenes has recently been investigated by our group introducing modifications of the standard methods. This includes, in particular, the basicity-driven heavy halogen migration, which allows the introduction of a functional group at a not directly accessible position. Then, some attentions were reported toward nucleophilic aromatic substitution and especially to a regio-controlled attack at heteroarenes. Bulky trialkylsilyl groups were used to shield a given position by steric congestion against both electrophilic and nucleophilic attack. Using different electrophiles, commercially available 2,6-difluoropyridine was selected as substrate for a large proliferation of derivatives through organolithium intermediates. To allow for more regioflexibility, one can either rely on protective groups or introduce iodine which will be subsequently submitted to a basicity gradient-driven relocation and eventually a halogen/metal exchange. A systematic investigation was undertaken to explore the scope and the limitations of this latter option. Di-, tri- and tetrahalopyridines are used to explore the substituent effect in nucleophilic substitutions with the pyridine ring. An activating substituent as chlorine directed the nucleophilic substitution at the vicinal fluorine atom. Unprecedented was the finding that bulky 3-trialkylsilyl group effectively shielded the fluorine at the adjacent 2- and 4-positions, reorienting the nucleophilic substitution to the 6-position. To exploit the regioselectivity established by the "silyl trick", some halopyridines, such as 2,4,5-trifluoropyridine or 2,4-dichloro-6-hydrazinopyridine, were prepared for the fist time. Highly substituted derivatives isolated during nucleophilic substitutions were the starting point for the development of more complex structures such 2-amino-5-bromo-4-chloro-6-fluoro-3-nitropyridine obtained by using some of the developed techniques.

EPFL2005

Chargement

Synthesis and Reactivity of 1-Allenyltriazenes

Farzaneh Fadaei Tirani, Loïc Nicolas Jeanbourquin, Rosario Scopelliti, Kay Severin

1-Aryl-3,3-dialkyltriazenes have received considerable attention in the context of synthetic and medicinal chemistry. In contrast, the chemistry of other unsaturated triazenes is largely unexplored. The synthesis of 1-allenyltriazenes is described. This new class of compounds can be obtained by base-induced isomerization of 1-alkynyltriazenes. The latter are accessible by reaction of alkynyl Grignard reagents with lithium amides and nitrous oxide. 1-Allenyltriazenes were found to be thermally labile, but they can be stored without degradation at lower temperatures. In the presence of ZnCl2, 1-allenyltriazenes rearrange into N-aminopyrazoles.

American Chemical Society2017

Chargement

Nitrogen-containing compounds are an important class of molecules in medicinal chemistry, chemical biology, biochemistry, material sciences or environmental sciences. Organic nitrogen occurs in many forms, ranging from small building blocks such as urea, amino acids, nucleotides, to complex natural products, drug molecules, proteins, nucleic acids, among others. The transformation of easily-accessed nitrogen-containing building blocks into more complex nitrogen-containing structures is therefore important for the synthesis of bioactive compounds or functional materials. Interested in donor-acceptor aminocyclopropanes and aminocyclobutanes, we first developed a Lewis-acid catalyzed formal [4+1] cycloaddition of donor-acceptor aminocyclobutanes with isocyanides, which resulted in the formation of cyclopentene-1,2-diamines. We then attempted to develop a formal [3+2] cycloaddition of donor-acceptor aminocyclopropanes with electron-deficient alkenes, which was mechanistically inspired by the Morita-Baylis-Hillman reaction. Apart from the donor-acceptor system, we were also attracted by simple aminocyclopropanes without electron-withdrawing group at vicinal position. We anticipated that the incorporation of cyclopropylamine into carboxylic-containing compounds followed by ring opening functionalization reactions could be used for the synthesis of more complex products. Therefore, we first disclosed an oxidative ring-opening strategy to transform acyl, sulfonyl or carbamate protected aminocyclopropanes into 1,3-dielectrophilic carbon intermediates bearing a halide atom (Br, I) and a N,O-acetal. Replacing the alkoxy group of the N,O-acetal was achieved under acidic conditions via an elimination-addition pathway, while substitution of the halides by nucleophiles was done under basic conditions via a SN2 pathway, generating a wide range of 1,3-difunctionalized propylamines. Based on the transformation described above, we further discovered an efficient synthesis of 4-amino thiochromans starting from simple aminocyclopropanes and thiophenols through a formal [3+3] annulation reaction. Next, we developed an oxidative ring-opening strategy to transform cyclopropylamides and cyclobutylamides into fluorinated imines. The imines can be isolated in their more stable hemiaminal form, with the fluorine atom installed selectively at the terminal position. Both cheap benzophenone with UV A light or organic and inorganic dyes with blue light could be used as photoredox catalysts to promote this process. Various fluorinated amines were then obtained by nucleophilic attack on the hemiaminals in one pot, giving access to a broad range of useful building blocks for medicinal chemistry. Finally, we turned our attention to the synthesis of diamines, which are essential building blocks for the synthesis of agrochemicals, drugs and organic materials, yet their synthesis remains challenging, as both nitrogen moieties need to be differentiated and diverse substitution patterns (1,2-, 1,3 or 1,4) are required. We described a new strategy giving access to 1,2-, 1,3- and 1,4- amido azides as orthogonally protected diamines based on the nitrogen-directed diazidation of alkenes, cyclopropanes and cyclobutanes.Other unsuccessful efforts over the last four years have also been described, together with some preliminary results of ring-opening cyanation and arylation reactions.

EPFL2022

Chargement

EPFL2022

Fluorine in an heteroaromatic context

Thierry Rausis

EPFL2005