The Vinylogous Anomeric Effect in 3-Alkyl-2-chlorocyclohexanone Oximes and Oxime Ethers

A series of trans-3-alkyl-2-chlorocyclohexanones, 2 (methyl, ethyl, isopropyl, and zerz-butyl), have been prepared and shown to exist predominantly in the diequatorial chair conformation except the tert-butyl derivative which prefers a twist-boat. Formation of the oximes and various oxime derivatives (methyloxime, silyloxime) results in a remarkable conformational inversion for the methyl, ethyl, and isopropyl systems. By analysis of vicinal interproton coupling constants it is believed that these compounds exist predominantly in the diaxial chair conformation. This is corroborated by an X-ray crystal structure of (E)-trans-5a which shows that the chair with diaxial substituents is indeed preferred in the solid state. A strong hyperconjugative stabilization of the axial conformation is proposed to be the origin of this preference which is termed the vinylogous anomeric effect.