This proposal presents methodology for the asymmetric 1,4-addition of silyllithiums as a latent hydroxyl equivalent to give access to optically pure beta-hydroxy carbonyls. This method will use a proline derivative as a chiral auxiliary bound directly to the silicon of the silyllithium as a means of inducing asymmetry into the addition. Alkylation or protonation of the resulting enolate allows control of the alpha-stereo center. The labile nitrogen silicon bond will make recovery of the chiral auxiliary as the hydrochloride salt, simple and high yielding. The resulting beta-silyl carbonyl can be transformed to the beta-hydroxy carbonyl via a Tamao oxidation. These beta-hydroxy carbonyl compounds are essential intermediates in the synthesis of dozens of important macrocyclic antibiotics.
