Stereoselective synthesis : studies involving dipole-stabilized carbanions alpha to nitrogen

Organolithiums are key reagents and intermediates in organic synthesis. An exciting and growing field is the use of organolithiums in enantioselective synthesis. The often complex nature of these compounds makes their implementation towards the synthesis of natural products or pharmaceutical targets a challenging yet rewarding endeavour. The ability of organolithiums to form carbon-carbon bonds in a stereoselective and predictable way is vital to their success in organic synthesis. The first chapter in this thesis summarizes the current mechanistic understanding of asymmetric carbon-carbon bond formation adjacent to nitrogen. A brief literature review is presented to illustrate the different ways in which a stereoselective lithiation/substitution reaction at carbon can occur. A review of the application of dipole-stabilized carbanions a to nitrogen used in the stereoselective synthesis of natural products is presented. The second chapter in this thesis describes a study of the use of N-Boc-3-pyrroline, and related compounds, as molecular scaffolds for the stereoselective synthesis of functionalized five-membered ring containing alkaloids. The asymmetric alkylation of N-Boc-3-pyrroline is possible for simple alkyl halides but only modest enantioselectivity can be obtained using chiral lithium amides or s-butyl lithium/(-)-sparteine as bases. More promising was the enantioselective alkylation of a protected 3-pyrroline building block 116. The assignment for the stereochemistry of the alkylated product from 116 and benzaldehyde was achieved by NMR techniques and conformational analysis. The work done on the synthesis of enantiomerically pure castanospermine analogs is also presented