Syntesis, Conformational Analysis, and Stereoselective Reduction of 14-Membered Ring 3-Keto Lactones

Article abstract of DOI:10.1021/jo00103a034

The synthesis of 3-oxo-13-tetradecanolide (5) and its 2-methyl and 2,2-dimethyl derivatives 7 and 8 have been carried out.The keto carbonyls in 5, 7, and 8 have been reduced with varying degrees of stereoselectivity.The stereoselectivity of the reduction depends on the counterion with the borohydride reducing agent, but selectivities approaching 100percent have been achieved for 5 and 7.The structure of the reduced products were determined by X-ray crystallography and chemical correlation.Heavy reliance on the stereoselectivity in the Frater dianion alkylation was used.The solution conformation of the β-keto lactones was found to be based on A both from NMR studies and molecular mechanics calculations.However, we are not able to predict the observed stereoselectivity in the hydride reduction of the ketones using this conformation.Thus we suggest the reduction proceeds through conformation B' in which the two carbonyls are chelated to the counterion.The conformations of the resulting alcohols are more complex and have both inter- and intramolecular hydrogen bonding which control the conformations.The use of polar maps to illustrate similarities and differences in conformations is demonstrated.These conformations are used to rationalize the physical and chemical properties of the β-keto and β-hydroxy 14-membered lactones.