Drawing on these insights, we propose that the reac=on of iTCO proceeds through an OH-assisted accelerated tautomeriza=on of ini=al 4,5-DHP click product to exclusively form 1,4-DHP, followed by 1,4-elimina=on to generate Pc (Fig. ). For DMT, two compe=ng pathways dictate the fate of this elimina=on product: aroma=za=on to Pa vs. intramolecular Michael addi=on of the direc=ng OH followed by oxida=on to Pia. Unlike methyl subs=tuents (aUer click with DMT), electron-withdrawing 2-pyridyl subs=tuents promote intramolecular Michael addi=on, resul=ng in the exclusive forma=on of Pi upon click with Pyr2 (1).