Synthesis and Reactivity of 1-Allenyltriazenes

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.

Novel Applications of Nitrous Oxide and Transition Metals for C-C and C-N Bond Formation

Gregor Kiefer

This thesis describes novel methods for and investigations into C–C and C–N bond formation reactions. Chapter 1 gives a very brief overview of established strategies for the formation of new C–C bonds in organic synthesis. In chapter 2, a multi‐step one‐pot synthesis is described. Arylalkynes and ethylene are converted to 2‐arylbutadienes by ruthenium catalyzed enyne metathesis. Upon addition of polyhalogenated substrates, the butadienes react in a 1,4‐atom transfer radical addition (ATRA) to yield 1,5‐dichloropen‐2‐enes. These form substituted vinylcyclopropanes via reductive 1,5 dechlorination with magnesium or manganese. Chapter 3 describes a study about two complex organometallic structures that form by reaction of rhodium(III) chloride with tert‐butylacetylene. The reaction products demonstrate the ability of rhodium to mediate various reactions of alkynes such as [2+2+1] cycloadditions, oxidative cleavages and others. Cobalt‐catalyzed reactions for C–C bond formation are reported in chapter 4. In the first part, the focus lies on the putative pre‐catalysts [CoX2(dppe)] (X = Cl, Br, I; dppe = diphenylphosphinoethane), which are used together with a reducing agent (e. g. zinc) in a wide range of C–C bond formation reactions. It is shown that they are, in reality, complex salts of the formula [CoX(dppe)2]2[X3Co(dppe)CoX3]. The second part describes the synthesis and characterization of the complexes [CoX(dppe)(PPh3)] and [CoX(dppe)(η4‐isoprene)]. Without addition of a reducing agent, these cobalt(I) complexes catalyze reactions that are usually accomplished with the catalyst system Co(II)/dppe/Zn. These results provide evidence that the active species in these reactions are indeed Co(I) complexes as supposed. In the fifth chapter, two methods for the use of nitrous oxide (N2O, laughing gas) in organic reactions are described. The challenge of using N2O in synthetic chemistry is to overcome its kinetic inertness. In the oxidative homo‐ and cross‐coupling of Grignard reagents, N2O takes the role of an oxidizing agent. The reactions proceed under mild conditions with copper, iron and cobalt salts as catalysts and exhibit high turnover numbers. The utilization of N2O has advantages compared to established methods with other oxidation agents such as oxygen. Furthermore, a procedure for the synthesis of triazenes from lithium dialkylamides, N2O and Grignard reagents is described. This method enables the synthesis of aryl and alkyl triazenes, but also alkenyl and alkynyl triazenes that are difficult to access via established procedures. Some alkynyl triazenes are selectively cytotoxic against certain cancer cell lines.

EPFL2015

Contributions to the Chemistry of N2O and 1-Alkynyltriazenes

Loïc Nicolas Jeanbourquin

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.

EPFL2018

Novel Applications of Nitrous Oxide and Transition Metals for C-C and C-N Bond Formation

Gregor Kiefer

EPFL2015