Using the dearomatization agent {WTp(NO)(PMe3)}, a dehydroindolizidine is prepared from the cyclocondensation of 2-methylpyrrole and methyl vinyl ketone (MVK) followed by reduction. When WTp(NO)(PMe3)(η2-benzene) is left in solution with 2-methylpyrrole the progress of the reaction can be monitored by 31P NMR. The reaction progresses through the conversion of an η2 bound pyrrole species (across carbons 4 and 5) that converts to an oxidative addition product across pyrrole’s N-H bond. Upon the addition of triflic acid, this tungsten hydride becomes a protonated hydride and eventually converts entirely to the desired η2 bound pyrrolium species across carbons 3 and 4. A structural feature of this dearomatized 2H-pyrrolium complex is the acidic proton on the nitrogen. Under weakly basic conditions, the nitrogen can be deprotonated, triggering a Michael addition with MVK. Once MVK has been incorporated, pyrrolidine is used to catalyze an aldol-like condensation reaction with the pendent methyl group of the pyrrole to form an indolizidine core (Figure 1). The resulting bicyclic system contains an a,b-unsaturated iminium group that can be fully reduced with tetrabutylammonium borohydride to form a dehydroindolizidine complex. Oxidation by NOPF6 liberates the free dehydroindolizidine.

Synthesis and isolation of a dehydroindolizidine from 2-methylpyrrole using the electron-rich tungsten dearomatization agent {WTp(NO)(PMe3)}

251st National Meeting (2016)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.