Studies in simultaneous generation of central and axial chirality via the Buchwald-Hartwig reaction

Robert Anthony Denning

doi:10.32920/ryerson.14646444.v1

Abstract

The Buchwald-Hartwig reaction has been investigated previously by the Viirre group to show that intramolecular cyclization using palladium and (R)-(+)-2-(diphenylphosphino)-2′-methoxy-1,1′-binaphthyl, can instill enantioselectivity. This system was continued to show that steric bulk on the 2’ position on the phenyl ring attached to the nitrogen malonamide can lock the rotation ending in a chiral axis. The diastereomers resulting from this chiral axis can be selectively formed when the substrate is 2-(2-bromobenzyl)-N1,N3-bis(2-(tert-butyl)phenyl)-2-methylmalonamide and using a similar ligand (R)-dicyclohexyl(2'-methoxy-[1,1'-binaphthalen]-2-yl)phosphane with enantio- and diastereoselectivities of 88% and 99% respectively. The work presented in this thesis continues on this class of substrates to include N,1-Di([1,1'-biphenyl]-2-yl)-3-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-3-carboxamide, as well as a newer class of monoamide substrates. The monoamide substrates allowed the interpretation of events occurring in the Buchwald-Hartwig reaction, ultimately showing that the chiral center on the substrate has some control as to the outcome of the chiral axis. Lastly, a timed sampling kinetics experiment was done to investigate if the enantiomers of the starting material were being consumed at different rates or if one diastereomeric product was being produced favourably. The kinetics experiment shows that the system does not have a preference as to the starting material or product being produced.

Highlights

This is known as the chiral center.1 1.1.1.2 Axial Chirality
The original synthesis was carried out using diethyl methylmalonate, starting with diethyl malonate would allow for further customizability of the alkyl group at the alpha carbon
The reaction proceeded smoothly and the resulting diethyl 2-bromobenzylmalonate was obtained in a good yield

Summary

Introduction

Stereochemistry is an area of chemistry devoted to understanding the differences between molecules which have the same atoms and bonds but differ in their three-dimensional structures. Isomers that differ in this way are known as stereoisomers.[1]. Point chirality exists when having four different groups bonded to a central tetrahedral carbon atom.[1]. The carbon atom bonded to F, H, ethyl and methyl is at the center of the chirality. This is known as the chiral center.1 1.1.1.2 Axial Chirality. When the chiral element is not on a single atom, but along a bond between two atoms, this is known as axial chirality.[2].

Objectives

Results

Conclusion