Accessing a Diverse Set of Functional Red-Light Photoswitches by Selective Copper-Catalyzed Indigo N-Arylation.

The ability to correlate the structure of a molecule with its properties is the key to the rational and accelerated design of new functional compounds and materials. Taking photoswitches as an example, the thermal stability of the metastable state is a crucial property that dictates their application in molecular systems. Indigos have recently emerged as an attractive motif for designing photoswitchable molecules due to their red-light addressability, which can be advantageous in biomedical and material applications. The lack of synthetic techniques to derivatize the abundant parent dye and a thorough understanding of the impact of structural factors on the photochemical and thermal properties hinder broad applications of this emerging photoswitch class. Herein, we report an efficient copper-catalyzed indigo N-arylation that enables the installation of a wide variety of aryl moieties carrying useful functional groups. The exclusive selectivity for monoarylation likely originates from a bimetallic cooperative mechanism through a binuclear copper-indigo intermediate. Functional N-aryl-N'-alkylindigos were prepared and shown to photoisomerize efficiently under red light. Moreover, this design allows for the modulation of thermal half-lives through N-aryl substituents, while the N'-alkyl groups enable the independent attachment of functional moieties without affecting the photochromic properties. A strong correlation between the structure of the N-aryl moiety and the thermal stability of the photogenerated Z-isomers was achieved by multivariate linear regression models obtained through a data-science workflow. This work thus builds an avenue leading to versatile red-light photoswitches and a general method for structure-property correlation that is expected to be broadly applicable to the design of photoresponsive molecules.

A Blueprint for Transforming Indigos to Photoresponsive Molecular Tools.

Indigo, one of the most ancient and abundant dyes in human history, has recently emerged as a potential functional motif due to its intriguing photochemical properties. This review aims to provide insights into both the preparation of these molecules and their utilization in molecular systems. First, the synthesis of the indigo core as well as available methods to derivatize indigo are described to outline synthetic strategies to build the desired molecular structures. Then, the photochemical behavior of indigos is discussed, with particular focus on E-Z photoisomerization and photoinduced electron transfer. Connections between the molecular structures and their photochemical properties are highlighted and serve as guiding principles for designing indigos to be applied as photoresponsive tools.

Red-light photoswitching of indigos in polymer thin films.

Through simple synthetic derivatisation, the parent indigo dye becomes a red-light E-Z photoswitch exhibiting negative photochromism and tuneable thermal isomerisation kinetics. These attributes make indigo derivatives extremely attractive for applications related to materials and living systems. However, there is a lack of knowledge in translating indigo photoswitching dynamics from solution to solid state - the environment crucial for most applications. Herein, we study the photoswitching performance of six structurally distinct indigo derivatives in five polymers of varying rigidity. Three key strategies are identified to enable efficient photoswitching under red (660 nm) light: (i) choosing a soft polymer matrix to minimise its resistance toward the isomerisation, (ii) creating free volume around the indigo molecules through synthetic modifications, and (iii) applying low dye loading (<1% w/w) to inhibit aggregation. These strategies are shown to improve both photostationary state distributions and the thermal stability of the Z isomer. When all three strategies are implemented, the isomerisation performance (>80% Z form in the photostationary state) is nearly identical to that in solution. These findings thus pave the way for designing new red-light photochromic materials based on indigos.

Electron-deficient olefin ligands enable generation of quaternary carbons by Ni-catalyzed cross-coupling.

A Ni-catalyzed Negishi cross-coupling with 1,1-disubstituted styrenyl aziridines has been developed. This method delivers valuable ß-substituted phenethylamines via a challenging reductive elimination that affords a quaternary carbon. A novel electron-deficient olefin ligand, Fro-DO, proved crucial for achieving high rates and chemoselectivity for C-C bond formation over ß-H elimination. This ligand is easy to access, is stable, and presents a modular framework for reaction discovery and optimization. We expect that these attributes, combined with the fact that the ligands impart distinct electronic properties to a metal, will support the invention of new transformations not previously possible using established ligands.

Directed nickel-catalyzed negishi cross coupling of alkyl aziridines.

Herein we report a nickel-catalyzed C-C bond-forming reaction between simple alkyl aziridines and organozinc reagents. This method represents the first catalytic cross-coupling reaction employing a nonallylic and nonbenzylic Csp(3)-N bond as an electrophile. Key to its success is the use of a new N-protecting group (cinsyl or Cn) bearing an electron-deficient olefin that directs oxidative addition and facilitates reductive elimination. Studies pertinent to elucidation of the mechanism of cross coupling are also presented.