Studies in simultaneous generation of central and axial chirality via the Buchwald-Hartwig reaction.
thesisposted on 22.05.2021, 12:46 authored by Robert Anthony Denning
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.