Studies on the Intermediates for Ruthenium Catalyzed Transformation of Alkyl Azides to N-H Imines

Abstract

Imines have been used to synthesize nitrogen containing natural products and biological active derivatives in organic chemistry. In general, N-substituted imines have been studied extensively, while N-unsubstituted imines (N-H imines) were relatively difficult to synthesize and manipulate due to its instability. Recently, our groups have developed a reaction to convert alkyl azide to N-H imine under neutral and mild conditions using ruthenium catalyst [Cp’Ru(CO)2]2 (Cp’ = η5-1-(phenylamino)-2,5-di-methyl-3,4-di-phenylcyclopentadienyl). Furthermore, we synthesized nitrogen containing compounds such as homoallylic amines, oximes, N-acyl imines, and isoquinolines by using N-H imines as electrophiles, nucleophiles, metal directing groups, and oxidation reduction reactions. However, this ruthenium catalytic systems had a limitation in that it could not be used in a one-step reaction due to interfere with the catalytic activity when acid or base was generated during the reaction. Therefore, a novel ruthenium complex [Cp^RuCl2]2 (Cp^ = η5-1-methoxy-2,4-di-tert-butyl-3-neopentylcyclopentadienyl) which overcomes the limitations of the conventional catalyst system was introduced and used synthesis of N-acyl enamines. However, the ruthenium catalyst [Cp^RuCl2]2 required high reaction temperature, and their catalytic properties have not yet been studied. In this thesis, synthesis of various ruthenium complexes containing sterically demanding ligand and catalytic reaction of alkyl azides with secondary amines under the ruthenium complex [Cp^RuCl2]2 were described. In chapter 2, synthesis of ruthenium bisammine complexes and reaction with aryl azides were described. Ruthenium tetraazadiene complexes were synthesized in the reaction of alkyl azides with ruthenium complexes [Cp^RuCl2]2 containing sterically demanding cyclopentadienyl ligands. Ruthenium bisammine complexes were formed in the simple reaction of the ruthenium tetraazadiene complexes with primary amine, and ruthenium complexes including various ligands such as carbon monoxide and phosphine could be synthesized through a ligand substitution reaction. Furthermore, ruthenium imido complexes and ruthenium tetraazadiane complexes could be synthesized by reacting with various aryl azides. N-Substituted imines can be synthesized via the reaction of alkyl azide with various primary amines using the ruthenium complexes. In chapter 3, synthesis of enamines using the reaction of an alkyl azide with a secondary amine under ruthenium catalyst were described. Conventional catalytic systems which convert alkyl azides to N-H imines were not suitable because the catalytic activity was deactivated under acid or base conditions. If acid or base was generated in a subsequent reaction, it could not be used for a one-step reaction. Therefore, there was limitation that N-H imine must be generated in those reactions. Especially, primary aliphatic aldimines which were produced with side reaction including decomposition could not be used in existing catalytic systems. The ruthenium complexes containing large cyclopentadienyl groups were able to proceed with the reaction using primary aliphatic aldimines because the catalytic activity was not affected by the acid or base. A wide range of substituted enamines were synthesized in high yields.