Ojima lactam

The Ojima lactam is an organic compound of some importance in the commercial production of Taxol. This lactam was first synthesized by Iwao Ojima. The organic synthesis is an illustration of asymmetric synthesis via a chiral auxiliary.

The reaction centers around an imine - lithium enolate cycloaddition. In order to ensure the correct stereochemistry (the phenyl group and the silyl ether must adopt a cis configuration) in the β-lactam a chiral auxiliary is used in the enolate synthesis. The enolate synthesis starts from glycolic acid. The hydroxyl group is protected by a benzyl group and the carboxylic acid is activated by reaction with thionyl chloride to the acid chloride. The acid chloride reacts with the chiral auxiliary trans-2-phenyl-1-cyclohexanol. The benzyl group is then removed and replaced by a TES silyl ether by reaction with triethylsilyl chloride. Reaction with phenyllithium affords the enolate.