Trifluorométhylthiolation par C-H activation et synthèse d’amines primaires en chimie en flux continu
This thesis is divided into two parts: primary amine synthesis from halides and Pd(II)-catalyzed trifluoromethylthiolation of C(sp3)-H bonds.  Both methods were developed in continuous flow chemistry.   Primary amines are important building blocks in synthetic chemistry. Therefore, numerous methods for the synthesis of primary amines have been developed. However, mono-alkylation of ammonia, is unreliable, as only modest yields are obtained, due to the poor nucleophilicity of ammonia and the formation of di- and tri-alkylated by-products. In this dissertation, flow chemistry has been used to develop a fast and efficient method for the direct amination of halides with ammonia. In addition, the methodology has been applied to an in-line synthesis showing the possibility for automated synthesis of various compounds.  There is a growing interest of the pharmaceutical and agrochemical industries toward the SCF3 moiety, due to its high lipophilicity and electron-withdrawing character. On the other hand, C-H activation has proven to be an elegant way to functionalize a molecule in an atom- and step-economical fashion. Although C-S bond formation by C-H activation has been relatively underexplored, Pr Pannecoucke and colleagues have elaborated a Pd(II)-catalyzed trifluoromethylthiolation of non-activated C(sp3)-H bonds using a bidentate directing group. Unfortunately, in somes cases, the yields remained modest and long reaction times are needed. Using a continuous flow approach, the reaction proceeded 120–429 times faster and afforded the desired product with improved yields.
amination C-H activation aminoquinoline trifluoromethylthiolation Flow chemistry amination halide