Year

2019

Degree Name

Doctor of Philosophy

Department

School of Chemistry and Molecular Bioscience

Abstract

An allenylamino alcohol was synthesised via a known borono-Mannich method in which the amine group was next to the allene bond. A novel 2-allenylaziridine was then successfully obtained from the allenylamino alcohol under mild reaction conditions. The reactivity of the aziridine towards a number of ring-opening reactions was investigated. However, these ring-opening reactions proved to be capricious, and for the majority of these reactions no product could be isolated, along with many side products being formed. Therefore, the investigation was shifted to synthesise 5-allenyloxazolidinones, which could participate in nucleophilic ring-opening reactions as equivalent analogues of 2-allenylaziridines. To obtain these unique allenyl heterocycles, a series of new allenylamino alcohols was required in which the hydroxy group should be adjacent to the allene bond, as the borono-Mannich method provides a nitrogen heteroatom next to the allene bond. The first examples of simultaneous control of diastereoselectivity and regioselectivity in zinc-catalysed allenylation reactions of N-protected α-amino aldehydes of high enantiomeric purity using an allenylboronic acid pinacol ester were developed to obtain a wide range of novel anti and syn allenylamino alcohols. The resulting allenyl products demonstrated high reactivity in NaH-induced and Au-catalysed intramolecular cyclisation reactions to obtain novel 5-allenyloxazolidinones and 2,5-dihydrofurans, respectively, in high yields. It was described that N-Bn allenyloxazolidinones can be selectively transformed into novel chiral 1,3-(E)-enynes upon treatment with an excess amount of NaH through a decarboxylative conjugate elimination process. Addition of an extra triple bond to the enynes by incorporation of either propargyl or propiolic groups provided a series of novel unconjugated (E)-enediynes. We explored the potential of these versatile scaffolds to undergo cascade Au(I)-catalysed cycloaromatisation reactions to offer enantioenriched versions of a wide range of biologically relevant isoindolines and isoindolinones. The cycloisomerisation reaction of the propargylated enediynes likely involved a known single cleavage skeletal rearrangement mechanism and gave the corresponding isoindolines. However, the N-propiolic enediynes underwent the Au(I)-catalysed cycloaromatisation through a new dual-gold reaction mechanism, which was supported by experimental, D-labeling experiments, and computational studies.

Share

COinS