Most contemporary chemical processes rely on non-renewable resources and reagents associated with negative impact on environment and human health. As a result, the safe-and-sustainable-by-design (SSbD) framework is launched to guide the innovation towards safe and sustainable materials and chemical products. Bisphenol A (BPA) is a widely used chemical in the production of plastics but known to activate oestrogen receptors and linked by numerous studies to adverse effects on both human health and the environment. Here we demonstrate how SSbD can lead a multidisciplinary study for the identification of non-oestrogenic BPA analogues suitable for incorporation into high-performance polymeric materials. Toxicological evaluation of a library of 172 bisphenols using an in silico model identified 20 promising candidates that are synthesized from renewable lignin-sourced feedstocks via benign dehydrative catalytic routes. Subsequent in vitro assessment of their oestrogen receptor activity identifies bisguaiacol F as optimal BPA analogue, which is incorporated into a polyester with attractive thermal stability and flexibility. This work demonstrates an effective workflow for the discovery of renewable and non-oestrogenic bisphenols by taking advantage of the synergy of synthetic chemistry, toxicology and computational modelling.

Non‐typical C‐functionalized sugars represent a prominent yet hardly accessible class of biologically‐active compounds. The available synthetic methodologies toward such sugar derivatives suffer either from an extensive use of protecting groups, requiring long and laborious synthetic manipulations, or from limited predictability and noncontrollable site‐selectivity of the employed C‐functionalization reactions. In this work, we disclose an alternative synthetic methodology toward nontypical sugars that allows facile, site‐selective, and stereocontrolled C‐functionalization of sugars through a traceless tethering approach. The described silyl‐based redox‐active tethering group appends directly to the unprotected sugar substrate and mediates the C‐functionalization reaction through a photochemically‐promoted 1,6‐hydrogen atom transfer (HAT) mechanism, while transforming into a readily‐removable silyl protecting group. The protocol is compatible with a variety of unprotected carbohydrate substrates featuring sensitive aglycons and a diverse set of coupling partners, providing a straightforward and scalable route to pharmaceutically relevant C‐functionalized carbohydrate conjugates.

Aromatic compounds serve as key feedstocks in the chemical industry, typically undergoing functionalization or full reduction. However, partial reduction via dearomative sequences remains underexplored despite its potential to rapidly generate complex three-dimensional scaffolds and the existing dearomative strategies often require metal-mediated multistep processes or suffer from limited applicability. Herein, a photocatalytic radical cascade approach enabling dearomative difunctionalization through selective spirocyclization/imination of nonactivated arenes is reported. The method employs bifunctional oxime esters and carbonates to introduce multiple functional groups in a single step, forming spirocyclic motifs and iminyl functionalities via N–O bond cleavage, hydrogen-atom transfer, radical addition, spirocyclization, and radical-radical cross-coupling. The reaction constructs up to four bonds (C−O, C−C, C−N) from simple starting materials. Its broad applicability is demonstrated on various substrates, including pharmaceuticals, and it is compatible with scale-up under flow conditions, offering a streamlined approach to synthesizing highly decorated three-dimensional frameworks.

Herein, we present a prominent metal-free C–N cross-coupling platform that enables access to carbamoyl- and ketoazides from isocyanides or silyl enol ethers and trimethylsilyl azide (TMSN3) with an aid of iodine(III) promoter. This offers a rapid route to a diverse set of synthetically valuable azide decorated fragments with excellent substrate scope and good to excellent yields. The disclosed platform exemplifies the use of TMSN3 for incorporation of the azide fragment without the loss of N2.

Unnatural α-amino acids constitute a fundamental class of biologically relevant compounds. However, despite the interest in these motifs, synthetic strategies have traditionally employed polar retrosynthetic disconnections. These methods typically entail the use of stoichiometric amounts of toxic and highly sensitive reagents, thereby limiting the substrate scope and practicality for scale up. In this work, an efficient protocol for the asymmetric synthesis of unnatural α-amino acids is realized through photoredox-mediated C-O bond activation in oxalate esters of aliphatic alcohols as radical precursors. The developed system uses a chiral glyoxylate-derived N-sulfinyl imine as the radical acceptor and allows facile access to a range of functionalized unnatural α-amino acids through an atom-economical redox-neutral process with CO₂ as the only stoichiometric byproduct.

Herein, we report a silver-catalyzed protocol for decarboxylative cross-coupling between carboxylic acids and isocyanides, leading to linear amide products through a free-radical mechanism. The disclosed approach provides a general entry to a variety of decorated amides, accommodating a diverse array of radical precursors, including aryl, heteroaryl, alkynyl, alkenyl, and alkyl carboxylic acids. Notably, the protocol proved to be efficient for decarboxylative late-stage functionalization of several elaborate pharmaceuticals, demonstrating its potential applications.

Herein, we report a mild and general protocol for chemoselective deacetylation of mixed acetyl- and benzoyl-protected carbohydrates under mild acidic conditions. The protocol allows quick access to partially protected carbohydrates, which serve as versatile synthetic intermediates during the total synthesis of various mono- and oligosaccharide targets. The applicability of the developed protocol was successfully demonstrated on a range of carbohydrate substrates of various configurations and substitution patterns featuring functionalized aliphatic and aromatic aglycones. The protocol has shown excellent compatibility with the widely used O-anomeric protecting groups, prespacer aglycones, and thioglycoside glycosyl donors.

The majority of contemporary chemical processes rely on non-renewable resources and reagents associated with negative impact on environment and human health. For this reason, the Safe-and-Sustainable-by-Design (SSbD) framework was launched by the European Commission to guide the innovation process towards green and safe chemical products. In this work, we demonstrate how SSbD guided a multidisciplinary study for facile identification of non-toxic bisphenol A (BPA) analogues suitable for incorporation into high-performance polymeric materials. Toxicological evaluation of a library of bisphenols with an in silico model identified promising candidates that were synthesized from renewable lignin-sourced feedstocks using benign catalytic routes. Subsequently, in vitro evaluation identified an optimal BPA analogue, that was successfully incorporated into a polyester with attractive properties for future consumer products. As such, the work showcases how the combination of synthetic chemistry, toxicology, and computational modelling enables an effective workflow towards renewable and inherently safe chemicals.

Herein, a straightforward synthetic approach for the construction of phenanthridin-6(5H)-one skeletons is disclosed. The developed protocol relies on palladium catalysis, providing controlled access to a range of functionalized phenanthridin-6(5H)-ones in 59-88% yields. Furthermore, plausible reaction pathways are proposed based on mechanistic experiments.

Alcohols and their derivatives are ubiquitous and versatile motifs in organic synthesis. Deoxygenative transformations of these compounds are often challenging due to the thermodynamic penalty associated with the cleavage of the C−O bond. However, electrochemically driven redox events have been shown to facilitate the C−O bond cleavage in alcohols and their derivatives either through direct electron transfer or through the use of electron transfer mediators and electroactive catalysts. Herein, a comprehensive overview of preparative electrochemically mediated protocols for C−O bond activation and functionalization is detailed, including direct and indirect electrosynthetic methods, as well as photoelectrochemical strategies.