Camphor-derived chiral auxiliaries in asymmetric synthesis

Molema, Warner Evert (1998) Camphor-derived chiral auxiliaries in asymmetric synthesis. PhD thesis, Rhodes University.

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The investigation has been focussed largely on the chemistry and stereo-directing potential of camphor-derived compounds. The major regioisomer produced on partial hydrolysis of N-benzylcamphorimide was identified, by one- and two-dimensional NMR and X-ray crystallography, as (+)-(1S,3R)-3-(N-benzylcarbamoyl)-2,3,3-trimethylcyclopentanecarboxylic acid, the methyl ester of which was shown to undergo an unexpected intramolecular rearrangement during LAH reduction to afford (1S,3R)-N-benzyl-3-hydroxymethyl-2,2,3-trimethylcyclopentane carboxamide. Several tartrate- and camphor-derived diols have been investigated as chiral auxiliaries in various asymmetric reactions of corresponding acetals of α,β-unsaturated aldehydes. MCPBA epoxidation of the tartrate-derived acetals afforded epoxy acetals in 4-12 % diastereomeric excess. The camphor-derived acetals were obtained solely as the exosubstituted diastereomers, the stereochemistry being confimned by two-dimensional NMR spectroscopy and X-ray crystallography. Simmons-Smith cyclopropanation of these camphor-derived acetals afforded cyclopropyl products with diastereoselectivities of 4% d.e. for the bomane-2,1O-diol acetal and 46 -> 99 % d.e. for the bomane-2,3-diol acetals. In order to increase diastereofacial selectivity, a camphor-derived diol having a bulky substituent at C-lO was prepared, viz., phenyl 2,3-dihydroxybomane-1Osulfonate, and α,β-unsaturated acetals of this diol were shown to undergo Simmons-Smith cyclopropanation with complete topological control (> 99% d.e.), the diastereoselectivities being conveniently determined by ¹ H and ¹³C NMR spectroscopy. Computer modelling, with the software package HYPERCHEM®, was used to explore the stereochemical aspects of the Simmons-Smith cyclopropanation, and hydrolysis of one of the cyclopropyl acetals has permitted the diastereoselective bias to be confirmed. (+ )-Pinane-2,3-diol was also investigated as a chiral auxiliary in the Simmons-Smith reactions of α,β-unsaturated aldehydes, and moderate diasteroselectivities (20-30 % d.e.) were observed. In a series of exploratory studies, the Diels-Alder reaction of the 2,3-dihydroxybomane-10-sulfonate acetal of trans-cinnamaldehyde with cyclopentadiene afforded a single cycloadduct, while OS04 dihydroxylation, MCPBA oxidation and alkylation of chiral acetals produced from both bomane-2,3-diol and phenyl 2,3-dihydroxybomane-1O-sulfonate were less selective.

Item Type:Thesis (PhD)
Uncontrolled Keywords:Asymmetric synthesis, Chirality, Camphor
Subjects:Q Science > QD Chemistry
Divisions:Faculty > Faculty of Science > Chemistry
Supervisors:Kaye, Perry
ID Code:3761
Deposited By: Mrs Carol Perold
Deposited On:23 Oct 2012 09:53
Last Modified:23 Oct 2012 09:53
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