Degree Name

Doctor of Philosophy


School of Chemistry


An investigation into the design and synthesis of helical chiral ligands for atropoenantioselective Suzuki reactions was undertaken. The chiral synthesis of 2,2'- bipyrrolidine was the subject of primary investigations which focused on methods to prepare the key intermediate alkene - (4E)-1,8-di(benzyloxy)-4-octene - in high geometrical purity. The trans selective Wittig reaction provided the optimum stereoselectivity (E:Z, 97:3), albeit with a low chemical yield (30%). Subsequent Sharpless asymmetric dihydroxylation afforded (4R,5R)-1,8-di(benzyloxy)-4,5- octanediol (73%, 97% ee) and separately, its S,S-enantiomer (77%, 87% ee). These diols can be easily elaborated to the target enantiomers of 2,2'-bipyrrolidine with preservation of stereochemical integrity.

The first two stereoselective syntheses of (2S,2'S)-2,2'-biindoline were concurrently performed using (2R,2'R)-2,2'-bioxirane and (2S,2'S)-N,N'-di-tert-butoxycarbonyl-2,2'- biaziridine as chiral precursors. The copper catalysed ring opening of each heterocycle with 2-bromophenylmagnesium chloride provided two pathways to (2S,3S)-1,4-di(2- bromophenyl)-2,3-butanediamine, which was regioselectively cyclised under microwave assisted palladium catalysis. The synthesis of (2S,2'S)-2,2'-biindoline was thus achieved in five-steps with an overall yield of 5% (>99% ee) from the bioxirane and in three-steps with in an overall yield of 15% from the biazidirine (>99% ee). Crystallographic analysis of the biindoline and its corresponding palladium(II) dichloride complex unequivocally confirmed the structure, enantiomeric purity and absolute stereochemistry of the molecule.

The chiral bioxirane was also used in a highly stereoselective four-step synthesis of (2S,2'S)-N,N'-di-tert-butoxycarbonyl-2,2'-bipyrrolidine using acetonitrile as the carbanion source for the ring opening reaction. A chiral copper(II) complex was subsequently prepared from the parent compound for application in oxidative aryl homo-coupling reactions, however its precise structure is yet to be determined.

The preparation of the analogous phospholane and arsolane monomers was investigated using a one-pot diGrignard cyclisation strategy. The reaction of 1,4-di(bromomagnesio)butane at 0 oC with PhPOCl2 and separately, PhAsO, provided 1- phenylphospholane 1-oxide and 1-phenylarsolane in unoptimised yields of 23% and 12% respectively. The same electrophiles in combination with 1-bromomagnesio-2-(2- (chloromagnesio)ethyl)benzene at -78 oC afforded racemic mixtures of 1- phenylbenzophospholane 1-oxide (46%) and 1-phenylbenzoarsolane (20%). The labile dimethylamino moiety was also accommodated as a P-substituent in the cyclisation of the latter diGrignard, providing racemic dimethylaminobenzophospholane 1-oxide in 60% yield.



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.