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.