Exploring Cyclization Strategies to Access Stemona Alkaloids: Subtle Effects Influencing Reactivity in Intramolecular Michael Additions

This report investigates the fundamental basis for rather surprising patterns of reactivity in Bronsted acid-mediated cyclizations of pyrrole substrates bearing pendant Michael acceptors that were identified during syntheses of Stemona alkaloids. Integrated experimental and theoretical studies reveal the profound influence that substituent effects have on the viability of these transformations. Additionally, we identify that electronic effects, in addition to barrier-lowering secondary orbital interactions within transition states, account for the exclusive preference for 7-endo-trig cyclizations over 6-exo-trig cyclizations.

Automated summary

This study investigates the surprising reactivity patterns in Bronsted acid-mediated cyclizations of pyrrole substrates with pendant Michael acceptors. Experimental and theoretical studies show the significant influence of substituent effects on the viability of these transformations. Electronic effects and barrier-lowering interactions within transition states are identified as the reasons for the exclusive preference for 7-endo-trig cyclizations over 6-exo-trig cyclizations.