Diastereoselective nucleophilic additions to 2-keto-4-methyl-1,3-dioxanes: 1,3-dioxanes as chiral auxiliaries

The diastereofacial selectivity of the reaction of various metal hydrides and Grignard reagents with 2-keto-4-methyl-1,3-dioxanes has been investigated. The stereochemical outcome of these highly diastereoselective additions (dr \u3e 90:10) was found to be consonant with Cram\u27s chelate model on the assumption that the metal hydride or Grignard reagent coordinates preferentially with the ring oxygen remote from the 4-methyl group. This methodology has been applied to the synthesis of α-hydroxy acids as well as to the synthesis of enantioenriched (S)-oxybutynin.