Tandem Intramolecular Diels-Alder/retro-Diels-Alder Approach to Dihydrofuro[2,3-c]pyrroles and Related Fused Dihydrofurans: Reac on Scope and Computa onal Insight

A one-pot cascade combining an intramolecular Diels-Alder cycloaddi on with a 3,6-di(2-pyridyl)-1,2,4,5-tetrazine-triggered retro-Diels-Alder sequence converts furan-alkyne precursors into par ally saturated, furan-fused heterobicycles, with 5/5 systems accessible while 5/6 analogues remain unreac ve under similar condi ons. The method requires an electron-withdrawing alkyne subs tuent and accommodates diverse bridging atoms (O, S, N-Boc, C) and C-5 furan subs tu on, providing modular access to compact sp 2 /sp 3 hybrid scaffolds. Computa onal (DFT) analysis iden fies intramolecular [4+2] cycloaddi on as the ratedetermining step and ra onalizes subs tuent effects.