Development of chiral cooperative catalysts featuring cation-binding sites and chiral pyridine-dihydroisoquinoline ligands for asymmetric reactions

Abstract

This dissertation discusses the development of a catalyst for the asymmetric reactions. Stereocontrol is crucial in several synthetic chemistry fields, including pharmaceutical, biological, agricultural, fragrance, and materials chemistry. Hence, a plethora of chiral organometallic complexes have been developed and investigated for numerous applications. Chapter 1 describes the background of asymmetric catalysis, introducing the fundamental concepts that govern it. In Chapter 2, cation-binding salen nickel catalysts were developed for the enantioselective alkynylation of trifluoromethyl ketones in high yield (up to 99%) and high enantioselectivity (up to 97% ee). The reaction proceeds with substoichiometric quantities of base (10-20 mol% KOt-Bu) and open to air. In the case of trifluoromethyl vinyl ketones, excellent chemo-selectivity was observed, generating 1,2-addition products exclusively over 1,4-addition products. UV-vis analysis revealed the pendant oligo-ether group of the catalyst strongly binds to the potassium cation (K+) with 1:1 binding stoichiometry (Ka = 6.6 × 105 M-1). Chapter 3 details the Enantioselective C(sp2)−H borylations of diarylmethylsilanes catalyzed by iridium complexes with chiral pyridine-dihydroisoquinoline (PyDHIQ) ligands. It was established that a higher selectivity was obtained for both electron-donating and electron-withdrawing substituents in this reaction, as compared to the results of a previously reported reaction. A gram-scale synthesis was conducted using 1 mol% of the catalyst to afford the desired chiral borylated organosilane product in 91% yield and >99% ee. The development of the PyDHIQ ligand for the enantioselective cross-coupling of secondary electrophiles with secondary nucleophiles in moderate yield (up to 94%) and high enantioselectivity (up to 96% ee) is discussed in Chapter 4.