NEW APPROACH FOR THE GENERAL-SYNTHESIS OF OXOTETRAHYDROINDOLES VIA INTRAMOLECULAR CYCLOADDITIONS OF AZOMETHINE YLIDES WITH TETHERED ALKYNES

A new method for the synthesis of oxotetrahydroindoles has been achiev ed employing an intramolecular dipolar cycloaddition approach involvin g mesoionic species (munchnones) with electron-deficient alkynes. The methodology is quite general and convergent as shown by the synthesis of a variety of tri- and tetrasubstituted oxotetrahydroindoles 18, 21, 24, 27, 30, and 34. LiI-based ester cleavage in the presence of an el ectrophilic acetylenic ketone was critical for formation of the requis ite cycloaddition substrates. The cycloaddition is virtually unaffecte d by the presence of gem-dimethyl groups in the side chain (cf. 38). T he presence of a substituted benzyl or a phenethyl moiety on nitrogen, a polarized acetylene, and an appropriate tether between dipole and d ipolarophile are essential for obtaining optimal efficiency.