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 achieved employing an intramolecular dipolar cycloaddition approach involving 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 electrophilic acetylenic ketone was critical for formation of the requisite cycloaddition substrates. The cycloaddition is virtually unaffected by the presence of gem-dimethyl groups in the side chain (cf. 38). The presence of a substituted benzyl or a phenethyl moiety on nitrogen, a polarized acetylene, and an appropriate tether between dipole and dipolarophile are essential for obtaining optimal efficiency.