A simple and convenient one-pot synthesis of substituted isoindolin-1-ones via lithiation, substitution and cyclization of N'-benzyl-N,N-dimethylureas

• Keith Smith,
• Gamal A. El-Hiti,
• Amany S. Hegazy and
• Benson Kariuki

Beilstein J. Org. Chem. 2011, 7, 1219–1227, doi:10.3762/bjoc.7.142

• 10.3762/bjoc.7.142 Abstract Lithiation of N'-benzyl-N,N-dimethylurea and its substituted derivatives with t-BuLi (3.3 equiv) in anhydrous THF at 0 °C followed by reaction with various electrophiles afforded a range of 3-substituted isoindolin-1-ones in high yields. Keywords: N'-benzyl-N,N-dimethylureas

• 6, and in a preliminary communication we reported that directed lithiation of various N'-benzyl-N,N-dimethylureas with t-BuLi (3.3 equiv) in anhydrous THF at 0 °C followed by reaction with various electrophiles afforded the corresponding 3-substituted isoindolin-1-ones in high yields [72]. We now

• process represented in Table 1 with other ring-substituted N'-benzyl-N,N-dimethylureas 19 (R = H, 4-OMe, 4-Me; Table 2). Each substrate was lithiated according to the standard procedure with t-BuLi (3.3 equiv) in anhydrous THF at 0 °C for 6 h, and then treated with various electrophiles. After work-up, as