Diseño y aplicaciones de nuevas familias de carbenos N-heterocíclicos quirales

Resumen

This Doctoral Thesis has been designed and performed with the aim of developing applications of interest in the field of enantioselective catalysis. In this context, new families of stable N-heterocyclic carbenes have been developed. The principal objective has been to study the possibility of introduction of chirality based on exocyclic N-dialkylamino groups or thioether-functionalized alkyl chains as substituents of one or more nitrogen atoms. In the general introduction, the memory collects generalities about N-heterocyclic carbenes, describing his nature, structure, stability, and the most relevant aspects of their reactivity and applications in enantioselective catalysis. In addition, the introduction includes the most relevant bibliographic references covering the structural diversity of this type of carbenes. The results section has been organized into independent chapters: Chapter I.2 covers the results obtained on the development of new triazolium salts from enantiopure hydrazines and their use as precursors of chiral N-heterocyclic carbenes. New 4-dialkylamino-1,2,4-triazol-5-ylidenes with a substitution pattern at C-1 including alkyl, aryl and thioeter-functionazided alkyl groups (heterobidentate C/S ligands) have been synthesised. Furthermore, the synthesis of their Rh(I) [Rh(NHC)Cl(COD)] complexes is described. Finally, the determination of the ¿-donor hability of the [Rh(NHC)Cl(CO)2] carbenes has been accomplished. Thus, the analysis of their infrared CO stretching frequencies indicates that, in general, nature of the substituents at N-1 has a negligible influence on the electronic properties of the carbene, with exception of the mixed ligands CNH(triazol)/S(thioeter), which show a lower s-donor ability. Chapter I.3 describes the design and synthesis of novel Ag(I) complexes containing mixed ligands based on chiral thioeter/N-heterocyclic carbene/thioeter (RS/NHC/SR) structures. Besides, their application as catalysts in the 1,3-dipolar cycloaddition reaction of imino-glycinates to dipolarophiles is described. The expected pyrrolidine derivatives were obtained with high yields, complete endo diastereoselectivity and promising enantioselectivities (ee up to 80%). Noteworthy, this reaction constitutes the first application of Ag(I) N-hetetocyclic carbenes (otherwise widely used as synthetic intermediates in the preparation of other metallic NHC complexes) in enantioselective catalysis. Chapter I.4 deals with the synthesis of a new family of achiral 2-fenil[1,2,4]triazo [4,3-a/f]piridinium salts and their metallic complexes. A comparative analysis reveals that the s-donor ability of these bicyclic carbenes is clearly higher than that of triazopyridin-5-yldene analogues, as a result of the annelation of the heterocycle. Furthermore, a preliminary approach to the development of a chiral version of this new type of carbenes is discussed. Chapter II collects the final results of a short stay in the laboratories of Prof. Steven Ley at Cambridge. In this work, a novel flow microwave device has been applied to the synthesis of 5-amino-4-cyanopyrazoles and the structurally more complex dimeric pyrazolopirimidines. The used flow system allows the isolation of these products with excellent purity without the need of traditional work-up or chromatographic purifications.