Design and Synthesis of Tris-Heteroleptic Bis-Cyclometalated Chiral-at-Rhodium Catalysts for Application in Asymmetric Catalysis

Chiral transition metal complexes represent a powerful class of catalysts for the asymmetric synthesis of optically active compounds. In recent years, Meggers and co-workers introduced a new class of iridium(III)- and rhodium(III)-based Lewis acid catalysts, in which the overall chirality exclusively originates from a stereogenic metal center, with all coordinating ligands being achiral. This thesis provides a synthetic approach to a previously elusive class of tris-heteroleptic bis-cyclometalated chiral-at-rhodium(III) complexes and demonstrates their application as chiral catalysts in asymmetric catalysis. Chapter 3.1 and 3.2. A method for the synthesis of a bis-cyclometalated rhodium complex containing two different cyclometalating ligands is developed. Preparation of this previously inaccessible family of tris-heteroleptic bis-cyclometalated rhodium catalysts was accomplished by a stepwise protocol that relies on the formation of an isolable mono-cyclometalated rhodium(III) species in the first step, which provided the opportunity to introduce a different second ligand in a subsequent second cyclometalation step. Resolution of the racemic complex into its individual lambda- and delta-enantiomers was achieved using an established chiral auxiliary-mediated approach. The final chiral-at-metal rhodium complex contains a cyclometalated 5-tert-butyl-1-methyl-2-phenylbenzimidazole, a cyclometalated 5-tert-butyl-2-phenylbenzothiazole, and two labile acetonitrile ligands, complemented by a hexafluorophosphate counterion, and was demonstrated to be a highly efficient catalyst for asymmetric [2+2] photocycloadditions. Chapter 3.3. An application of chiral bis(oxazoline) ligands as C2-symmetric chiral auxiliaries for the synthesis of enantiopure bis-cyclometalated rhodium(III) complexes is described. Bis(oxazolines) are versatile chiral ligands for asymmetric catalysis, but have not been used for the resolution of racemic mixtures of transition metal complexes. Due to their C2-symmetry, chiral bis(oxazolines) are particularly useful for the synthesis of nonracemic transition metal complexes with lower symmetry and this is demonstrated for the synthesis of an enantiomerically pure rhodium(III) complex containing two different cyclometalated ligands. Chapter 3.4. The developed synthetic method for the preparation of bis-cyclometalated rhodium(III) complexes with two different cyclometalating ligands was further improved and the modularity of the procedure demonstrated by the addition of two new catalyst derivatives which, in addition to a cyclometalated 5-tert-butyl-1-methyl-2-phenylbenzimidazole, contained a cyclometalated 3,5-diphenyl-1H-pyrazole or a sterically more demanding 1-mesityl-3,5-diphenyl-1H-pyrazole ligand. Both catalysts were readily accessible in an enantiomerically pure fashion (>99% ee) via the previously established chiral bis(oxazoline) mediated strategy. Chapter 3.5. A non-C2-symmetric and sterically demanding chiral-at-rhodium(III) catalyst is demonstrated to efficiently catalyze the highly enantioselective alpha-fluorination (12 examples, up to >99% ee) and alpha-chlorination (12 examples, up to 98% ee) of N-acyl pyrazoles in high yields. Comparison of the catalytic performance with related C2-symmetric rhodium catalysts revealed the clear superiority of the non-C2-symmetric design for the presented alpha-halogenation reactions, which are generally featured by a very simple synthetic protocol. Conversion of the alpha-halogenated products into the corresponding esters with almost no epimerization was achieved and allowed the synthesis of valuable chiral compounds for subsequent chemical transformations