Camphor-derived chiral auxiliaries: a synthetic, mechanistic and computational study

• Main Author: Duggan, Andrew Robert
• Format: Others
• Language: English
• Published: Rhodes University 2007
• Subjects: Camphor; Chirality; Asymmetric synthesis
• Online Access: http://hdl.handle.net/10962/d1006772

A broadly based approach has been undertaken to the development and use of camphor derivatives as chiral auxiliaries in asymmetric synthesis – an approach which has embraced synthetic, mechanistic and computational studies. The unambiguous characterization of mono- and dihydroxy-derivatives, obtained by reduction of chiral camphor ether dimers, has been achieved through detailed one- and two-dimensional NMR spectroscopic analysis. The resulting data has been used to establish both the regio- and stereochemistry of the hydroxyl groups. A camphor-derived cyclic iminolactone has been shown to provide a convenient platform for the synthesis of chiral α-amino acids, stereoselective monoalkylation of the iminolactone affording a range of products in yields of 52 - 65 % with up to 85 % d.e. The attempted development of chiral bifunctional Morita-Baylis-Hillman substrates has revealed an unexpected equilibration between isomeric bornane 2,3-diol monoacrylates via acid-catalysed intramolecular transesterification. A detailed [superscript 1]H NMR-based kinetic study of the rearrangement in various media and at various temperatures has permitted the determination of the kinetic and thermodynamic parameters. A computational study at the DFT level has been used to explore the potential energy surfaces of the acid-catalysed and uncatalysed transesterification of the monoacrylate esters. The theoretical data supports the involvement of cyclic intermediates and has provided a rational basis for predicting the favoured reaction pathways. Novel camphor-derived phenyl sulfonate esters and N-adamantylsulfonamides have been synthesised for use as chiral auxiliaries in the Morita-Baylis-Hillman reaction. Modeling at the Molecular Mechanics level has provided useful insights into possible conformational constraints and an adamantyl sulfonate auxiliary has been successfully used in the stereoselective synthesis of a range of products, generally in excellent yield and with up to 95 % d.e.