Chiral Diamine Derivatives: Synthesis and Evaluation as Transient Directing Groups (TDGs) in C(sp3)-H activation reactions of α-keto amides

Abstract

This research project has been developed in the Department of Organic Chemistry I at the Faculty of Chemistry in Donostia, under the guidance of Professor Maria Antonia Mielgo Vicente. Research carried out in this project belongs to the Organic Chemistry field, more precisely, to the area of asymmetric catalysis. This work’s aim has been to explore the reactivity of α-keto amides in C(sp3)-H activation reactions catalysed by Pd metal and transient directing groups (also abbreviated as TDG), more specifically, the direct arylation of more remote positions than the β site, in other words, the γ and δ positions. The reactions have been carried out with two types of ligands, first with commercially available achiral ligands (glycine and β-alanine), then with the designed chiral TDGs. Hence, first the α-keto amides (K1 and K2) have been synthesised by adapting the protocols previously used in the research group. Afterwards, the synthesis of L1, L2 and L3 (chiral diamine derivatives) has been explored, adapting other methods described in the literature. L1 and L2 have been synthesised, although the protocols and yields require optimisation; however, L3 has not been obtained. Lastly, the C(sp3)-H activation reactions have been explored using different TDGs and commercially available aryl iodide as the electrophile. The racemic reactions have been explored using achiral TDGs glycine and β-alanine. Then the designed L1 and L2 TDGs have also been tested. All TDGs analysed promote the C(sp3)-H arylation reaction with different conversions. Furthermore, the designed TDGs promote the selective γ-arylation of the α-keto amides but in the explored conditions the conversion is not complete and the observed enantioselectivity did not match the expected results.