The stereochemistry of 2,4- and 2,3-disubstituted-γ-butyrolactones

Abstract

Relative configurational assignments have been made to the 2,4-dimethyl-(7), 2,4-di-t-butyl-(8), 2,4-diphenyl-(9), 4-methyl-2-phenyl-(10), and 2-methyl-3-phenyl-(31)γ-butyrolactones on the basis of the stereoselective synthesis of their cis-isomers, from the corresponding disubstituted but-2-en-4-olides (2)–(5) and 2-methylene-3-phenyl-γ-butyrolactone (41) by hydrogenation over palladium. The characteristic features from the ¹H n.m.r. spectra of the cis- and trans-isomers of (7)–(10) have been employed to assign relative configurations to the 2-methyl-4-phenyl-(11), 2,4-diethyl-(12), 2-ethyl-4-methyl-(13), and 2-butyl-4-methyl-(14)γ-butyrolactones. Equilibration studies on seven 2,4-disubstituted γ-butyrolactones [(7)–(10) and (12)–(14)] indicate that (i) the free energy differences between cis- and trans-isomers are small, and (ii) the cis- is thermodynamically more stable than the trans-isomer in all cases. The opposite situation is true of the 2-methyl-3-phenyl-γ-butyrolactones (31) where the trans-isomer is found to predominate at equilibrium. ¹H N.m.r. spectroscopic data suggest that the conformational behaviour of the five-membered ring in 2,4-disubstituted γ-butyrolactones is different for diastereoisomers but is not influenced to any great extent by the nature of the substituent groupings.