Year

2023

Degree Name

Doctor of Philosophy

Department

School of Chemistry and Molecular Bioscience

Abstract

Five-membered cyclic sulfamidate imines—the unsaturated analogues of the well-established synthetic precursor cyclic sulfamidates—have attracted increasing interest from synthetic chemists within the last two decades, and the recent developments involving this intriguing scaffold is summarised in Chapter 1. Featuring a highly reactive imine functionality, these stereodefined heterocycles are popular substrates in various transition metal-catalysed asymmetric reactions such as hydrogenation, transfer hydrogenation, and nucleophilic addition. On the other hand, the nucleophilic reactivity of these cyclic imines, enabled by the acidic proton(s) at the α-position to the imine functionality, have also been elegantly demonstrated in several organocatalysed cascade transformations. This manuscript describes the deployment of this versatile scaffold and related derivatives in various stereoselective palladium(0)-catalysed reactions.

The development of a Pd-catalysed asymmetric allylic alkylation reaction using these cyclic sulfamidate imines as substrates is described in Chapter 2, being the first literature example successfully utilising the nucleophilicity of these heterocycles in a transition metal-catalysed protocol. Under the optimised reaction conditions, utilising a chiral Trost ligand, a wide range of imines underwent the transformation with various allyl carbonates and 1,3-dipole precursors to afford the allylated products in high yields and high enantioselectivities overall, which can be further elaborated to afford valuable synthetic intermediates such as chiral sulfamidates and β-amino alcohols. Intriguingly, the formation of the N-allylated product was observed for a few substrates, followed by their conversion to the corresponding C-allylated derivatives overtime in an enantioselective manner.

The preliminary investigation of a Pd-catalysed (3 + 2) cycloaddition of cyclic sulfamidate fused vinyl aziridines—a significant departure from the simple vinyl aziridines typically utilised in the literature—with activated olefins is outlined in Chapter 3. It was found that even though the desired heterobicyclic cycloadduct could be obtained in high yields under several examined reaction conditions (up to 89%), the diastereocontrol of the transformation has been unsatisfactory, with the best result obtained being only 2.3 : 1 dr. Regardless, these preliminary results successfully established a proof of concept and may serve as a foundation for further studies of this precursor.

The successful adoption of cyclic sulfamidate imine-derived 1-aza-1,3-dienes as a unique dipolarophiles in an enantio- and diastereoselective Pd-catalysed (3 + 2) cycloaddition with vinylcyclopropanes is discussed in Chapter 4. The optimised protocol, featuring a chiral SEGPHOS ligand, tolerated a wide range of 1-azadienes, affording densely functionalised spiroheterocycles containing three stereogenic centres in good to high yields, with high enantio- and diastereoselectivities overall. Further chemo- and stereoselective manipulations targeting these available functional handles allow an additional stereogenic centre to be readily installed.

FoR codes (2020)

340209 Organometallic chemistry, 340503 Organic chemical synthesis, 340601 Catalysis and mechanisms of reactions

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Unless otherwise indicated, the views expressed in this thesis are those of the author and do not necessarily represent the views of the University of Wollongong.