Reductive Coupling of Phthalimides with Ketones and Aldehydes by Low-Valent Titanium: One-Pot Synthesis of Alkylideneisoindolin-1-ones

The
reductive coupling of phthalimides with ketones and aldehydes
by Zn-TiCl4 in THF gave two- and four-electron reduced
products, 3-hydroxy-3-(1-hydroxyalkyl)­isoindolin-1-ones and alkylideneisoindolin-1-ones,
selectively by controlling the reaction conditions. Therefore, the
one-pot synthesis of alkylideneisoindolin-1-ones from phthalimides
was effected by this reaction. Although the alkylideneisoindolin-1-ones
prepared from phthalimides and aldehydes were formed as mixtures of
geometric isomers in most cases, the geometric ratios could be increased
by reflux in cat. PPTS/toluene. After the isomerization, the E-isomers of N-methyl substituted alkylideneisoindolin-1-ones
(X = Me, R1 = R, R2 = H) and the Z-isomers of N-unsubstituted alkylideneisoindolin-1-ones
(X = H, R1 = H, R2 = R) were obtained preferentially.

在四氢呋喃(THF)中，以锌-四氯化钛(Zn-TiCl4)体系实现邻苯二甲酰亚胺(phthalimides)与酮(ketones)、醛(aldehydes)的还原偶联反应，通过调控反应条件可选择性得到两电子还原产物3-羟基-3-(1-羟烷基)异吲哚啉-1-酮(3-hydroxy-3-(1-hydroxyalkyl)isoindolin-1-ones)与四电子还原产物亚烷基异吲哚啉-1-酮(alkylideneisoindolin-1-ones)。据此，该反应可实现由邻苯二甲酰亚胺一锅法制备亚烷基异吲哚啉-1-酮。尽管由邻苯二甲酰亚胺与醛制备的亚烷基异吲哚啉-1-酮在多数情况下以几何异构体混合物形式生成，但通过催化量(cat.)对甲苯磺酸吡啶盐(PPTS)/甲苯回流可提升其几何异构体比例。异构化后，N-甲基取代的亚烷基异吲哚啉-1-酮（X = Me, R1 = R, R2 = H）优先生成E型异构体，而N-未取代的亚烷基异吲哚啉-1-酮（X = H, R1 = H, R2 = R）则优先生成Z型异构体。