Unusual tethering effects in the Schmidt reaction of hydroxyalkyl azides with ketones: cation-pi and steric stabilization of a pseudoaxial phenyl group.

The Lewis acid-promoted reactions of chiral 2-aryl-3-azido-1-propanols with 4-substituted cyclohexanones lead to iminium ethers and ultimately caprolactams (following a hydrolysis step). In this study, it is shown that these reactions afford variable ratios of products, depending on the electronic nature of the phenyl group. These results are interpreted in the context of a cation-pi stabilizing effect in the product-determining reaction intermediate. Remarkably, the best selectivity was obtained when an azidopropanol reagent containing a quaternary center was used; a control experiment showed that the high selectivity observed in this result depended upon the free rotation of the pseudoaxial aromatic group in the intermediate that affords the major product.