Reactions of Sulfonylphthalide with Diverse Activated Imines for the Synthesis of Enaminophthalides, Spiro-isoquinolinones, and Homalicine Natural Products

The reactivity of the Hauser-Kraus (H-K) donor, 3-sulfonylphthalide, with various activated imines under basic conditions is demonstrated. The reaction of 3-sulfonylphthalide with Boc-protected aldimine provides a rapid access to 1,2-imine adducts and alkylidenephthalides depending upon the stoichiometry of the base. The alkylidenephthalides could be transformed to ketophthalides, a new class of phthalides, on acid hydrolysis, which upon reductive cyclization using Zn/AcOH afforded the natural product homalicine. On the contrary, the Boc-protected isatinimines undergo an efficient H-K annulation to provide spiro-isoquinolinone-oxindoles in excellent yields. However, the corresponding conjugated ketimines afforded Michael adducts, which were converted to the corresponding alkylidenephthalides under TBAF conditions.

Automated summary

The reactivity of Hauser-Kraus (H-K) donor, 3-sulfonylphthalide, with various activated imines under basic conditions is demonstrated. Depending upon the stoichiometry of the base, the reaction of 3-sulfonylphthalide with Boc-protected aldimine provides access to 1,2-imine adducts and alkylidenephthalides. The alkylidenephthalides can be transformed to ketophthalides, and Boc-protected isatinimines can undergo efficient H-K annulation to provide spiro-isoquinolinone-oxindoles.