N–Phenyl Pyrroloimidazolone Derivatives for Stereoselective Birch Reduction-Alkylation and Chiral Imidazolylidene-Iridium Complexation

Abstract

This thesis describes the synthesis and use of an N– based proline–derived directing group towards the Birch reduction, diastereoselective alkylation, and the synthesis of NHC–iridium complexes that are precursors for the study of intramolecular aryl C–H activation. A pair of ortho–benzoate esters containing epimeric pyrroloimidazolone chiral auxiliaries underwent sequential Birch reduction and diastereoselective alkylation to provide products ranging from a 50:50 to 95:5 dr for the anti– epimer, and 88:12 to >95:5 diastereomeric ratio (dr) for the syn– epimer. Single crystal X–ray analysis of key anti–epimer–derived products, along with the comparison of the optical rotation measurements of enantiomers that were prepared from the syn–or anti– starting materials to its known enantiomer confirmed the stereoselectivity of the products. This work includes related Schultz stereoselective Birch reduction alkylation of anisole with a chiral benzamide except that the pyrroloimidazolone replaces the achiral methoxy group and serves as the stereodetermining element. In addition, the synthesis and evaluation of the N–phenyl iridium complex derived from the annulated aminal with syn–stereochemistry in the backbone was achieved. Exposure of the neutral Ir–complexes to anionic nucleophiles such as MeLi resulted in an increase of electron density at the Ir atom that initiated C–H bond activation. Lastly, a N–heterocyclic carbene ligand derived from the N–benzyl analogue of the auxiliary was also investigated. Attempts to design a monodentate ligand as well as a bidentate ligand bearing an alcohol side chain were both shown to be unsuccessful at this time.