Regio- and Stereoselective Synthesis of Isoindolin-1-ones through BuLi-Mediated Iodoaminocyclization of 2‑(1-Alkynyl)benzamides

A simple
and straightforward synthesis of isoindolin-1-ones is
reported. Exclusive N-cyclization of the amide functional
group, an ambident nucleophile, was accomplished for the cyclization
of 2-(1-alkynyl)­benzamides using n-BuLi-I2/ICl. The methodology works with the primary amide and affords the
desired isoindolinones in yields of 38–94%. Interestingly,
the isolated products exhibit a Z-stereochemistry
across the CC double bond. The reaction mechanism involving
the formation of either a vinylic anion or an intimate ion pair intermediate
is proposed.