アミド修飾したアリル化剤を利用するα-メチレン-γ-ブチロラクトンおよびα-メチレン-γ-ブチロラクタムの選択的合成

抄録

α-Methylene-γ-butyrolactone is a pharmaceutically important motif which is often found in bioactive molecules. Allylation of ketones or aldehydes with β-ester-functionalized allylating agents is known to be one of the reliable synthetic methods for the methylene lactones, while reactions using β-amido-functionalized ones, which provide the precursors for methylene lactones and analogous methylene lactams, have not been fully explored. Herein, we summarized our research on the development of selective syntheses of α-methylene-γ-butyrolactones and α-methylene-γ-butyrolactams. Addition of β-amido-functionalized allylstannanes to N-carbonyl imides was catalyzed by indium chloride and zinc chloride, providing methylene-lactam-fused spirolactones through unique ring opening-reclosure. These allylstannanes were applied to the highly enantioselective syntheses of methylene lactones and methylene lactams, in which indium-catalyzed asymmetric allylation of α-ketocarbonyl compounds was established. We also developed β-amido-functionalized allylboronates as an alternative allylating agent. These reagents showed sufficient nucleophilicity toward N-carbonyl imides in the presence of catalytic zinc bromide and basic additives, and the resulting adducts were employed as a common intermediate for the syntheses of methylene-lactone- and methylene-lactam-based spiro compounds. Furthermore, the remarkable water-stability of the allylboronates led to the development of asymmetric allylation of acetophenones in water. The reaction was catalyzed with zinc hydroxide and a chiral aminophenol reagent, affording a variety of homoallylic alcohols with up to 98% ee.