From Photoswitch to Polycycle: Structure-Reactivity Relationships in the Photoinduced Isomerization-Cyclization of Amino(hetero)arylidene-thiazolidine-2,4-diones.

Abstract

We report a comprehensive study of the photoinduced isomerization-cyclization cascade of o-amino(hetero)arylidenethiazolidine-2,4-diones (Het)Ar-TZDs 1, combining computational, synthetic, and kinetic investigations. Time-dependent density functional theory (TD-DFT) calculations were used to predict absorption maxima and to elucidate key structure-property relationships, highlighting the dominant influence of substitution at position 4 of the aromatic ring of 1. Guided by these results, a broad library of o-amino-TZDs 1 was designed and synthesized, including heteroaryl analogues. Photochemical investigations demonstrated that the sequence is highly robust, overall, proceeding efficiently across a wide range of substrates and displaying a broad tolerance toward variations in their electronic properties or substitution patterns. A detailed kinetic analysis using ex situ and in situ 1H NMR experiments was conducted and enabled a quantitative comparison of reaction efficiencies as a function of substituents on the aromatic ring, the TZD core, and the exocyclic double bond, across series 1(a) to 1(d). Overall, this work establishes a fine structure-reactivity framework for this photochemical cascade, identifying the key parameters governing its efficiency.