Design, synthesis and applications of tetradentate transition metal complexes towards asymmetric alkylations

Abstract

Controlling the absolute stereochemistry of molecules is a major challenge to contemporary chemists. Achieving high enantioselectivity with catalytic amounts of a chirality transfer (or inducing) agent, and the ease of regenerating such catalysts is yet another challenge. Due to the involvement of various transition metal complexes, the relatively young field of enantioselective catalysis has emerged as a powerful tool for organic chemistry. In our efforts towards the synthesis of a universal catalyst, O'Donnell Schiff base derived tetradentate ligands were shown to catalyze dialkylzinc additions to aldehydes in high selectivity. The three pot synthesis of bifurcated dipeptides in very good yields and the mechanistic aspects of diethylzinc additions to aromatic aldehydes are described in this dissertation. The chiral Lewis acidic behavior of these ligands was supported by a mechanistic study done examining the nonlinear effect. Unlike bidentate ligands such as (-)-3-exo-N,N-dimethylaminoisoborneol (DAIB), the tetradentate ligands in this study show strictly linear behavior. Also, the linear free energy relationships studied by observing the enantioselectivity with respect to electron donating or withdrawing substituents on the benzaldehyde substrates supported a Lewis acid role for the zinc complexes. A negative slope was obtained when ee's were plotted against sigma values of the substituted benzaldehydes. Since they bind to various bivalent transition metal cations, these ligands can be viewed as privileged structures, and may potentially become catalysts for various asymmetric reactions. As catalyst screening can be greatly facilitated by heterogeneous catalysis, solid phase ligands were synthesized using Wang and Merrifield resin supports. The synthetic methodology was developed using a diarylketimine linker with the aid of on-bead characterization techniques such as 13C NMR and UV-VIS spectroscopy. The ligands were shown to asymmetrically catalyze the alkenylzinc additions to aromatic aldehydes. In situ generation of alkenylzinc reagents by boron to zinc transmetalation followed by the addition to benzaldehyde in the presence chiral zinc complexes resulted in enantiomerically enriched allylic alcohols. The preliminary results for this transformation resulted in 3:1 selectivity in favor of S-isomer.