Conformationally Controlled Chiral Phenanthrolines for Asymmetric Catalysis

Author

Irina Dotsenko, University of the Pacific

Date of Award

2014

Document Type

Dissertation - Pacific Access Restricted

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Pharmaceutical and Chemical Sciences

First Advisor

Vyachelsav V. Samoshin, Ph.D.

First Committee Member

Andreas H. Franz, Ph.D.

Second Committee Member

Liang Xue, Ph.D.

Third Committee Member

Pasit Phiasivongsa, Ph.D.

Fourth Committee Member

Wade A. Russu, Ph.D.

Abstract

Asymmetric catalysis is vitally important for modern organic chemistry. However, many chiral catalysts are readily available only in a single absolute configuration. This often prevents practical access to both enantiomers of a product. To address this shortcoming, we propose a novel type of accessible ligands based on the structure of trans-5,6-disubstituted-5,6-dihydro-1,10-phenanthroline. Conformers of this molecule have opposite twist in the bipyridine fragment (opposite helicity or axial chirality). Thus, a relative stabilization of one or the other conformer of the same chiral precursor could potentially give access to two ligands with opposite axial chirality and hence to two catalysts with opposite enantioselectivity.

We proposed structural modifications of substituents attached to 5,6-dihydro-1,10- phenanthroline as a convenient and reliable approach for stabilization of one or another conformer. To validate this strategy, multiple oxygen- and sulfur-substituted ligands were synthesized and fully characterized. In particular, their conformational behavior was studied by 1H NMR. Some ligands and their metal complexes were designed and proved to be conformationally (axially) constrained. Chiral resolution of these ligands through separation of their diastereomeric derivatives was accomplished, resulting in material of high optical purity. The absolute configuration of chiral elements (centers and axis) were established by 1H NMR, CD and X-ray analysis.

Metal complexes with a range of novel chiral 5,6-dihydro-1,10-phenanthrolines were assessed as chiral catalysts for the asymmetric alkylation of aldehydes, Henry reaction and allylic substitution. Moderate to high activities were achieved in all catalytic transformations while low to moderate degree of enantioselectivity was observed. The results of asymmetric catalysis confirmed the crucial role of the twist in the ligand’s bipyridine moiety (of its sign and magnitude) in the induction of stereoselectivity.

Exploring an undesired aromatization of products in cleavage of 5,6-epoxy-5,6- dihydro-1,10-phenanthroline with various thiols in presence of base, we developed a new simple procedure and synthesized a broad library of novel valuable ligands: 5-aryl(alkyl)sulfanyl-1,10-phenanthrolines and bis(1,10-phenanthrolines). Other functional groups attached to the thiol moiety allow using these products as building blocks for versatile ligands and in functionalization of surfaces. Besides, the new sulfur- substituted derivatives were found to be potent modulators of fungal glycosidases.

Pages

244

Recommended Citation

Dotsenko, Irina. (2014). Conformationally Controlled Chiral Phenanthrolines for Asymmetric Catalysis. University of the Pacific, Dissertation - Pacific Access Restricted. https://scholarlycommons.pacific.edu/uop_etds/4232