Unexpected stability of δ-lactones with axial substituents rather than equatorial ones. Conformational evaluation by molecular mechanics and molecular orbital calculations

Abstract

A 1:1 mixture of the trisubstituted δ-lactones 5a and 5b was subjected to thermodynamically equilibrated conditions to give predominantly 5b with axial substituents rather than 5a with all equatorial ones, in contrast to the Prelog-Djerassi lactone derivatives 3a and 3b. Further surprisingly, it has been found that the disubstituted lactone 15 also adopts a half-chair conformation with axial substituents. The conformational analyses of these compounds by molecular mechanics and molecular orbital calculations have emphasized gauche effects and electrostatic interactions as a cause of the preference for axial conformers.