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

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.