Chiral bicyclic keto lactones: determination of the absolute configuration by the study of chiroptical properties and chemical correlation

摘要

Chiral bifunctional oxabicyclodecanediones (keto lactones) were synthesized from the corresponding bicyclo[3.3.1]nonane diones 1-5 by employing a regioselective Baeyer-Villiger oxidation. Enantiomers with high enantiomeric excess were obtained by chiral HPLC enantiomer separation on microcrystalline, triacetylcellulose column. Circular dichroism spectra of molecules containing two chromophores, namely a carbonyl and lactone in one molecule, were studied. The conformational analysis was performed with the aim to apply the octant and lactone sector rules for the determination of the absolute configuration. Ab initio and molecular mechanics calculations revealed that for all compounds investigated a single conformer, that is c-tb for 1a-3a and 1b-2b, and c-tc for 4a, tc-tc for 5a is prevalent in the gas phase at room temperature. The applicability and limitations of the semi-empirical rules was demonstrated. The enantiospecific synthesis of enantiomerically enriched keto lactones 1-2a and 1b-2b from the corresponding enantiomeric ketones unambiguously led to the final proof of the absolute configurations. (C) 2004 Elsevier Ltd. All rights reserved.