Lewis Acid-Mediated Acetal Substitution Reactions: Mechanism and Application to Asymmetric Catalysis

Substitution reactions of acetals with carbon nucleophiles are fundamental and conventional organic reactions. We succeeded in the preparation of an optically active acetal, which reacted with a silyl enol ether smoothly to afford the desired adducts in racemic forms. By comparison of the ees of the products with the ees of the recovered acetals, we concluded that the aldol-type reactions proceeded not via direct displacement (SN2) or contact ion pairs (intimate ion pair) (SN1) but by a free oxocarbenium ion (SN1) mechanism. Next, a study to achieve asymmetric catalysis of the acetal substitution reactions was conducted. After many trials, it was found that a chiral niobium complex prepared from pentamethoxyniobium [Nb(OMe)5] and a tetradentate BINOL derivative could achieve high enantioselectivities. Asymmetric aldol-type reactions of acetals with silyl enol ethers proceeded smoothly to afford the corresponding aldol-type adducts in good yields with high enantioselectivities.