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

Abstract

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.

Visible light-responsive materials: the (photo)chemistry and applications of donor–acceptor Stenhouse adducts in polymer science

“…DASA stability and their tendency to undergo the retro-reaction as a function of different substitution patterns on the triene bridge have also been studied by DFT calculations. 73 In addition, acid triggered in situ formation of Stenhouse salts from DASAs was observed, which most likely proceeded via a retro-reaction to the furan adduct with subsequent release of furfural. 107 A mechanistic characterization of this dissociative side reaction has not yet been reported.…”

“…Limited DASA stability from retro-formation of the starting materials has also recently been observed or predicted in studies of various small molecule DASAs in solution. 36,73,79,107 It was reported that a DASA composed of an indoline donor and a Meldrum's acid-based acceptor with methyl substitution at position 5 of the triene bridge led to release of the amine and recovery of the furan adduct when in solution overtime. 36 This reaction was shown to be faster in more polar solvents such as methanol.…”

“…Recent findings raise the concern that DASA stability even in the dark, is limited for some DASAs under certain conditions, and that, for example, a reversion to its starting materials can occur. 36,73,107,138 It still needs to be investigated in more detail how general this problem is and when exactly it occurs. Apart from this, further studies are required focusing on elucidating system-dependent degradation pathways both in the dark and under light irradiation.…”

“…35,37 Moreover, substitutions along the triene also induce substantial effects on the photoswitching kinetics, absorption wavelengths, dark equilibrium and stability of the formed DASAs, but research in this direction is still in its early stages. 36,73,74…”

“…6c). 35,49 Substitutions along the triene structure can also affect the DASA thermodynamic equilibrium by either increasing the energy of the closed form relative to the open form, 36 or vice versa , 73,74 depending on the substituent size and position on the backbone.…”