Borilación C(sp2)-H de arenosdesarrollo y aplicaciones

Résumé

The central objectives of this Doctoral Thesis lie in the broad field of transition-metal catalyzed transformations directed towards organic synthesis, and more specifically in C-H functionalization reactions and asymmetric catalysis using Suzuki-Miyaura cross-coupling reactions. Chapter I describes a new methodology for the nitrogen-directed C-H borylation of arenes. A rational design led to the use of modified Ir catalysts containing hemilabile N/N ligands. The strategy relies on the temporary generation of coordination vacancies necessary to enable the required directing effects. Thus, using pyridino-hydrazones as the hemilabile ligands, the desired ortho-selective Ir-catalyzed borylation has been performed using 2-arylpyridines(isoquinolines) and aromatic N,N-dimethylhydrazones as substrates. The borylated products have demonstrated a high synthetic value, being easily transformed into products of interest. Additionally, the development of modified, more efficient ligands allowed the use of pinacolborane as the borylation reagent, thereby increasing the atom economy of the process. Finally, this technique has been applied to the ortho,ortho'-diborylation of N,N-dimethylhydrazones, that, combined with a sequential dissymmetric functionalization with two different electrophiles, provides a very efficient route to densely functionalized arenes. In Chapter II, the 2'-borylated 1-arylisoquinolines obtained in Chapter I have been used as substrates in asymmetric Suzuki-Miyaura cross-couplings with aryl halides, in a process that represent a singular case of dynamic kinetic resolution (DKR). These reactions have been performed using Pd(0) catalysts with axially chiral MOP-type ligands. The best ligands to date contain additional P-stereogenic phosphines, leading to coupling products with enantiomeric excesses of up to 68%. This method constitutes a contribution to the few available methods for the asymmetric synthesis of heterobiaryls.