Development of enolate chemistry and total syntheses of bioactive natural products

Methodologies with chiral enolates including the stereoselective construction of the quaternary carbon, rearrangement of the vinylketene N,O-acetals, the remote stereoinduction with vinylketene silyl N,O-acetals, and the construction of 1,2-diols having the tertiary alcohol have been developed to apply to the natural product synthesis. Each isomer at the quaternary carbon has been synthesized from one enantiomer of α,β-unsaturated imide by choosing whether alkylation of the dienolate anion or rearrangement of the vinylketene N,O-acetal with MeAlCl₂. The vinylketene silyl N,O-acetals possessing the chiral auxiliary reacted with aldehydes in the presence of TiCl₄ to realize the stereocontrol at the y and 8 positions. Aldol reactions with lactate having the chiral auxiliary provided the 1,2-diols possessing the tertiary alcohol. The major stereoisomer depended on the chiral auxiliary and the protective group on the hydroxy group of lactate. These methodologies realized the short-step syntheses of natural products.