An Efficient Entry to syn- and anti-Selective Isoindolinones via an Organocatalytic Direct Mannich/Lactamization Sequence

An organocatalytic direct Mannich–lactamization sequence for the syntheses of pharmacologically important enantioenriched isoindolinones is reported. The method utilizes simple α-amino acids to deliver syn- and anti- selective isoindolinones with remarkably high enantioselectivity (up to >99% ee) in good to excellent yields and diastereomeric ratios. The overall sequence involves one C–C and two C–N bond forming events in one pot starting from inexpensive starting material.本研究报道了一种用于合成具有重要药理活性的对映富集异吲哚啉酮的有机催化直接曼尼希-内酰胺化串联反应。该方法以简单易得的α-氨基酸为底物，可得到兼具顺式与反式选择性的异吲哚啉酮，其对映选择性极佳（最高可达>99%对映体过量值（enantiomeric excess，ee）），且收率介于良好至优异水平，非对映选择性比例优异。该整体串联反应可从廉价起始原料出发，在一锅反应内完成一次C-C键与两次C-N键的构建。