Organocatalyzed Asymmetric Michael Addition of 1‑Acetylindolin-3-ones to β,γ-Unsaturated α‑Ketoesters: An Access to Chiral Indolin-3-ones with Two Adjacent Tertiary Stereogenic Centers

Asymmetric Michael addition of 1-acetylindolin-3-ones
to β,γ-unsaturated α-ketoesters was investigated
for the synthesis of chiral indolin-3-ones with two adjacent tertiary
stereogenic centers. Under the catalysis of a chiral bifunctional
squaramide derived from l-tert-leucine,
a wide range of 1-acetylindolin-3-ones and β,γ-unsaturated
α-ketoesters were well-tolerated in this transformation to provide
the corresponding novel densely functionalized chiral indolin-3-one
derivatives in high yield with excellent diastereo- and enantioselectivity
under mild reaction conditions.

为合成具有两个相邻叔手性中心的手性吲哚啉-3-酮类化合物，本研究考察了1-乙酰基吲哚啉-3-酮（1-acetylindolin-3-ones）与β,γ-不饱和α-酮酸酯（β,γ-unsaturated α-ketoesters）之间的不对称迈克尔加成（Asymmetric Michael addition）反应。在由L-叔亮氨酸（l-tert-leucine）衍生得到的手性双功能方酰胺（squaramide）催化下，该转化对多种底物均具有良好的兼容性，可在温和反应条件下以高收率得到对应的新型高官能团化手性吲哚啉-3-酮衍生物，且产物展现出优异的非对映选择性与对映选择性。