Matthew Neil Hopkinson

This perspective provides an overview of recent methods (since 2023) enabling the degradation of PTFE at low temperature (≤100 °C) forming useful fluoride salts, which in some cases can be upcycled into valuable fluorinated fine chemicals.

Gamification is a well-established strategy for increasing students’ motivation and engagement. With the aim of building a sense of community among incoming Chemistry undergraduates, we previously developed an interactive game, CHEMmunicate, where teams of students compete to draw organic structures using only yes/no questions. In addition to their social benefits, the sessions also had a positive influence on students’ learning of organic chemistry with “post-game discussions” of fundamental concepts in particular providing a useful tool for reinforcing and revising key material from the core lectures. In contrast to the rounds of CHEMmunicate, however, these informal, non-competitive discussions did not incorporate elements of gameplay and thus did not fully benefit from the well-established advantages of game-based learning. In this work, we have reimagined the “post-game discussion” element of the sessions, introducing competitive online quizzes alongside rounds of CHEMmunicate. Working in their teams, students compete to answer questions related to the molecules they have just drawn with points being awarded for giving the correct answers in the fastest time. Here, we provide information and tips for those interested in incorporating similar sessions into their own teaching practice. Moreover, through analysis of anonymous questionnaires and a focus group, insights into students’ experiences are discussed.

The combinatorial explosion inherent to multi‐component systems limits their experimental exploration and ultimately chemical discovery. Here, we introduce a statistics‐based group‐testing strategy, which we couple with luminescence quenching assays to efficiently identify cooperative molecular interactions. Utilizing the quenching of a photosensitizer as a quick readout for chemical activity, 4,950 substrate pairs were screened in only 504 experiments, enabled through a combinatorial design theory‐based pooling approach and iterative deconvolution. Therefore, two algorithms—a greedy algorithm for group design and an iterative sectioning deconvolution method to resolve active pairs—were implemented. Fifteen cooperative pairs were identified, and the nature of their interactions and the resulting electronic perturbations were investigated. In a systematic follow‐up screen, it was found that the identified active pairs exhibit high reactivity towards a broad group of reaction partners. One such pair led to the discovery of a bench‐stable reagent, enabling efficient and regioselective trifluoromethylthiolation reactions. This work establishes a broadly applicable framework for accelerating the discovery of cooperative reactivity through optimized experimental designs.

The combinatorial explosion inherent to multi‐component systems limits their experimental exploration and ultimately chemical discovery. Here, we introduce a statistics‐based group‐testing strategy, which we couple with luminescence quenching assays to efficiently identify cooperative molecular interactions. Utilizing the quenching of a photosensitizer as a quick readout for chemical activity, 4,950 substrate pairs were screened in only 504 experiments, enabled through a combinatorial design theory‐based pooling approach and iterative deconvolution. Therefore, two algorithms—a greedy algorithm for group design and an iterative sectioning deconvolution method to resolve active pairs—were implemented. Fifteen cooperative pairs were identified, and the nature of their interactions and the resulting electronic perturbations were investigated. In a systematic follow‐up screen, it was found that the identified active pairs exhibit high reactivity towards a broad group of reaction partners. One such pair led to the discovery of a bench‐stable reagent, enabling efficient and regioselective trifluoromethylthiolation reactions. This work establishes a broadly applicable framework for accelerating the discovery of cooperative reactivity through optimized experimental designs.

The combinatorial explosion inherent to multi-component systems limits their experimental exploration and ultimately chemical discovery. Here, we introduce a statistics-based group-testing strategy, which we couple with luminescence quenching assays to efficiently identify cooperative molecular interactions. Utilizing the quenching of a photosensitizer as a quick readout for chemical activity, 4,950 substrate pairs were screened in only 504 experiments, enabled through a combinatorial design theory-based pooling approach and iterative deconvolution. Therefore, two algorithms—a greedy algorithm for group design and an iterative sectioning deconvolution method to resolve active pairs—were implemented. Fifteen cooperative pairs were identified, and the nature of their interactions and the resulting electronic perturbations were investigated. In a systematic follow-up screen, it was found that the identified active pairs exhibit high reactivity towards a broad group of reaction partners. One such pair led to the discovery of a bench-stable reagent, enabling efficient and regioselective trifluoromethylthiolation reactions. This work establishes a broadly applicable framework for accelerating the discovery of cooperative reactivity through optimized experimental designs.

Polytetrafluoroethylene (PTFE) is a highly versatile material that has found widespread application owing to its exceptionally high chemical resistance and thermal stability. However, these properties mean that PTFE disposal is an energy intensive process, producing fluorinated materials which pose serious concerns regarding toxicity and environmental persistence. Herein we report a straightforward mechanochemical approach for the reductive defluorination of PTFE generating an environmentally benign mixture of elemental carbon and sodium fluoride. The process employs cheap and readily available chunks of sodium metal, proceeding rapidly at room temperature, in the absence of any organic solvent to form sodium fluoride (NaF) in 98% yield. The fluoride generated in the process can be directly upcycled into fine chemicals through in situ mechanochemical fluorination reactions, delivering valuable sulfonyl fluoride and acyl fluoride products in excellent yields.

Light-mediated methodologies for the reduction of acylazolium species generated during N-heterocyclic carbene (NHC)-catalyzed reactions have been developed. Employing the simple amine, DIPEA, as the terminal reductant, products resulting from overall 2-electron or 4-electron-reduction processes could be obtained using either a photocatalytic approach under blue light irradiation or directly under UV-A light irradiation without an additional photocatalyst. Moreover, under the same photocatalyst-free conditions, UV-A-light-mediated reduction could be achieved using triethylsilane as the only reductant with subsequent desilylation and NHC elimination with fluoride delivering the corresponding aldehyde product.

CO methylenation mediated by α-silyl organo-alkali metal reagents, namely Peterson methylenation, is a textbook organic reaction that has been widely employed in synthetic chemistry for over 50 years. The process is performed over two steps, by isolating the β-silyl alcohol intermediate generated via nucleophilic addition and then subjecting it to elimination. The choices of alkali metal and external Lewis base ligand play a critical role in the elimination step, but the reasons remain poorly understood. In this work, we have systematically investigated the metal identity and ligand effects in CO methylenation reactions mediated by MCH₂SiMe₃ (M = Li; Na; K). We observed pronounced alkali metal cation and ligand effects on the methylenation performance, with K⁺ and tetrahydrofuran (THF) being optimal. Based upon these learnings, a straightforward new methylenation method has been designed involving carbonyl addition with LiCH₂SiMe₃, followed by in situ addition of KOtBu in THF, facilitating facile transmetallation-enabled elimination. This strategy enables the methylenation to be achieved in one pot, whilst circumventing the use of KCH₂SiMe₃. Excellent yields have been achieved for a range of ketones (including enolizable examples) and aldehydes. The method uses commercial solvents and reagents, and can be performed without any requirement for stringent drying or deoxygenation.