Christian Victor Stevens

The development and optimisation of a safe and scalable continuous flow Vorbrüggen protocol for the synthesis of environmentally improved fluoroquinolones.

A significant challenge associated with antibiotics, and active pharmaceutical ingredients in general, is their intentional design for high stability, which promotes environmental persistence and contributes to the development of antibiotic resistance. Ciprofloxacin, a widely used fluoroquinolone antibiotic, exemplifies this issue. Using the benign by design (BbD) approach, ciprofloxacin was redesigned into an environmentally improved fluoroquinolone molecule, termed Cip‐hemi. In this design, ciprofloxacin was modified by replacing the persistent cyclopropyl group at the N1 position with a tetrahydrofuran moiety, thereby creating a degradable linker. Herein, we report the development of an efficient and robust synthetic platform to access the Cip‐hemi scaffold, along with the preparation of a series of novel derivatives. These molecules are developed with a dual‐purpose design: to restore high‐level antibacterial action while ensuring rapid degradation in the aquatic environment. The optimized synthetic strategy minimizes the use of hazardous solvents and largely avoids labor‐intensive purification by flash chromatography, providing a streamlined approach for the preparation of environmentally improved fluoroquinolones.

In this work, a metallaphotoredox C(sp ² )–C(sp ³ ) coupling between aryl (pseudo)halides and alkyl boronic acid pinacol esters was optimized using a two‐stage workflow. In the first stage, high‐throughput experimentation (HTE) is used in conjunction with Bayesian optimization (BO) to select promising discrete parameter values for five categorical reaction variables, including photocatalyst, nickel precursor, nickel ligand, solvent, and amine, from a search space of 30,000 conditions within 120 experiments per substrate across four aryl (pseudo)halides, representing <0.5% of the space. Crucially, the approach proved able to autonomously identify reactivity trends reported in literature without any prior knowledge. In the second stage, the optimal conditions for each substrate are transferred to flow, where eight continuous parameters, including residence time, reaction stoichiometry, temperature, and light intensity, are fine‐tuned. The sequential strategy delivers DMF‐ and precious‐metal‐free protocols for bromides and chlorides and, for the first time, extended this coupling reaction to aryl triflates.

In this work, a metallaphotoredox C(sp ² )–C(sp ³ ) coupling between aryl (pseudo)halides and alkyl boronic acid pinacol esters was optimized using a two‐stage workflow. In the first stage, high‐throughput experimentation (HTE) is used in conjunction with Bayesian optimization (BO) to select promising discrete parameter values for five categorical reaction variables, including photocatalyst, nickel precursor, nickel ligand, solvent, and amine, from a search space of 30,000 conditions within 120 experiments per substrate across four aryl (pseudo)halides, representing <0.5% of the space. Crucially, the approach proved able to autonomously identify reactivity trends reported in literature without any prior knowledge. In the second stage, the optimal conditions for each substrate are transferred to flow, where eight continuous parameters, including residence time, reaction stoichiometry, temperature, and light intensity, are fine‐tuned. The sequential strategy delivers DMF‐ and precious‐metal‐free protocols for bromides and chlorides and, for the first time, extended this coupling reaction to aryl triflates.

A metal‐free, rapid, and chemoselective protocol for the nitro reduction of aromatic compounds is reported using tetrahydroxydiboron as reducing agent and 4,4′‐bipyridine as organocatalyst. This method provides the transformation to aromatic amines with high functional group tolerance in good to excellent yields, under mild conditions (ambient temperature) and water as solvent.

Accurate determination of a molecule's thermodynamic properties using quantum chemistry methods is crucial for developing kinetic models. A vital step in the quantum chemical workflow is calculating torsional energy profiles to apply the one-dimensional hindered-rotor approximation. However, these profiles are typically obtained by performing rotational scans using density functional theory (DFT) methods, which adds high computational cost to the workflow. Here, we assess the performance of the semiempirical GFN2-xTB method for rapid generation of these torsional profiles by calculating the contributions of GFN2-xTB and B3LYP profiles to the enthalpy, entropy, heat capacity, and Gibbs free energy of molecules. Several correction methods to improve the results are proposed and evaluated. It is found that correcting the energy profiles based on their second derivative at the optimized-geometry point yields the most accurate results. This optimal correction method results in a mean absolute error on the Gibbs free energy at 1000 K of 0.43 kJ mol^-1 for a hydrocarbons data set and 0.93 kJ mol^-1 for a data set of nitrogen-containing compounds. In conclusion, the GFN2-xTB method, when combined with a suitable correction method, can accelerate the generation of hindered rotor profiles by a factor of 700, with only a minor loss of accuracy.

Since the resurgence of interest in chitinous materials in the 1970s, significant efforts have been devoted to their utilization and valorization. With the availability of ISO 13485-certified chitinous materials suitable for biomedical use, these polymers are no longer merely waste-derived byproducts. Chemical derivatization has resulted in a large and diverse body of literature on chitinous-based materials. Nevertheless, the reproducibility of reported results remains a persistent challenge, often arising from inadequate structural and compositional characterization. To address this limitation and to facilitate unambiguous structure-property correlations, this review proposes a first set of minimum NMR reporting standards, illustrated through practical examples. In addition, it provides guidance on the effective use of classical liquid-state NMR techniques, such as ¹H, ¹³C, ¹H-¹H COSY, ¹H-¹³C HSQC, HMBC and H2BC, as well as emerging diffusion-based methods for the characterization of unknown chitinous materials and their derivatives.

This review provides chemists with an introduction to Bayesian optimization. Core principles and techniques are explained alongside a comprehensive overview of applications in both batch and flow, focusing on practical aspects.

The use of weak, inexpensive bases in the assembly of late-transition metal NHC complexes represents a most promising synthetic strategy. We now disclose the use of gaseous and aqueous ammonia as bases for the continuous-flow synthesis of these complexes with Au, Pd, and Cu metal centers. The fully homogeneous system enables reactions to proceed under milder, faster, and more concentrated conditions than state-of-the-art methods.