Highly substituted cyclohexanones and bicyclic derivatives: synthesis, structure and NMR studies

Abstract

A new family of 3-aryl-3,5,5-trisubstituted cyclo-hexanones have been synthesized and studied by proton and carbon-13 NMR spectroscopy, [diagram and equation on PDF]. These highly substituted ketones have been prepared by the conjugate addition of an aryl Grignard reagent to an unsaturated cyclohexanone. The yield of 1,4-addition product is enhanced by the use of low temperatures and a copper(I) catalyst. Derivatives of these ketones were prepared by a modified Wolff-Kishner reaction (to afford cyclohexanes) and a Wittig reaction (to afford exo-methylenecyclohexanes). A new family of Bicyclic Hydrocarbons has also synthesized, [diagram on PDF]. These have been prepared by the acid-catalyzed cyclization of the carbinol or derived olefins formed by Grignard addition to the parent cyclohexanones. Both concentrated sulfuric acid and trifluoroacetic acid have been used to effect the cyclization, with the latter providing greatly increased yields of Bicyclic Hydrocarbons. The cyclohexanones and derivatives have been subjected to study by proton and carbon-13 NMR spectroscopy. The observed, anomalous proton chemical shifts (e.g., see compound Ia) have been interpreted in terms of structural effects. The structural requirements for the observation of an anomalous high-field methyl shift have been delineated as: (a) the cyclohexanone must be tetrasubstituted at C-3 and C-5, (b) at least one substituent must be aryl, and (c) the carbonyl function (or indeed any sp²-hybridized carbon atom) at C-1 is not essential for the observation of the anomalous proton shifts....