Mechanism of the Aza-Piancatelli Reaction: Scope and Limitations of Furan Substitution in Donor–Acceptor Stenhouse Adduct Synthesis

[Image: see text] The aza-Piancatelli reaction has been widely used to synthesize donor–acceptor Stenhouse adducts (DASAs), a new class of molecular photoswitches with unique properties. However, the substitution pattern of furan cores has been limited to position 3, as 3,4-disubstituted furans remain unreactive. Herein, we explore the aza-Piancatelli reaction mechanism using density functional theory (DFT) calculations to understand the influence of the different substituents on the reactivity. We found that all the reaction pathways are kinetically accessible, but the driving force of the reaction is lost in disubstituted furans due to the loss of conjugation in the DASA products. Finally, a simple model is proposed to guide the design of synthetic routes using this reaction.