The work reported in this manuscript concerns the development of a new approach to a family of natural butyrolactames, with a high therapeutic potential, based on a [2+2] cycloaddition reaction followed by a ring expansion. In the main part, a procedure for the preparation of highly functionalized cyclobutanones by [2+2] cycloaddition between chiral enols ethers and functionalized ketenes has been developed. With this method, a variety of cyclobutanones were obtained in a highly chemo-, regio- and stéréosélective manner. The ring expansion of the previously prepared cyclobutanones to obtain the butyrolactame skeleton of (–)-Salinosporamide A was next investigated. The last part of this manuscript consists in a study of the [2+2] cycloaddition reaction between ketene and enol ether activated by a Lewis acid in catalytic amount. This first study seems to point out that an activation of [2+2] cycloaddition reaction is possible when a sterically hindered enol ether is used.
