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A practical synthesis of bicyclo(3.3.1)nonan-9-one was examined. A room temperature-atmospheric pressure PtO2/H2 hydrogenation was performed on the mixture of bicyclo(3.3.1)nonan-9-one. Results indicate that the reaction was rapid in methanol but was accompanied by ca. 5% of ketone reduction which was reversed with a small amount of Jones reagent. The method used inexpensive amounts of readily available reagents and was performed on a ca 20 g product scale in 47% yield.

Large-scale distillation is a challenge in many respects. Particularly difficult is the purification by distillation of a compound with limited thermal stability. This article describes various aspects of these difficulties with some possible solutions. Special emphasis is placed on the collaboration of different disciplines to find pragmatic solutions to these challenges. The purification of diketene in quantities of several 1000 ta-1 is an excellent example to illustrate the different requirements. Although the distillation of diketene has been carried out by several companies for many years, there are still some aspects that deserve special attention., (Copyright 2024 Mehmet Ogün Biçer, Erik von Harbou, Andreas Klein, Hilke-Marie Lorenz, Christoph Taeschler. License: This work is licensed under a Creative Commons Attribution 4.0 International License.)

Industrial representatives from the Swiss chemistry ecosystem met to formulate unmet needs in the field of sustainability and share the content of the exchange. The aim is to spark inspiration and trigger ambitious and pre-competitive projects collectively at the interface of the academic and industrial worlds, with the hope to profoundly change the current practices and provide an answer to some of the most urgent environmental challenges., (Copyright 2023 F. Gallou, E. Godineau, O. Enger, F. Ewald, C. Herber, S. Hildbrand, N. Künzle, M. Marty, Thomas Netscher, Kurt Püntener, M. Reiter, C. Taeschler, C. Karate. License: This work is licensed under a Creative Commons Attribution 4.0 International License.)

Grignard reactions are an efficient way to form carbon-carbon bonds with widespread applications in large-scale processes. Classically, the electrophiles of choice to form ketones from Grignard reagents are acid chlorides. The reactions are typically catalyzed by additives such as CuCl to increase selectivity and yields. This work was focused on the use of acetic anhydride as an alternative to acetic chloride in the synthesis of 4-fluoro-2-(trifluoromethyl)acetophenone ( 3 ), a useful intermediate for the synthesis of active agricultural ingredients. The use of acetic anhydride as an electrophile not only equals but also surpasses acetic chloride in yield and selectivity, while also being more tolerable toward higher reaction temperatures. Furthermore, the reaction was performed in the absence of any additive, making it a highly attractive process for large-scale production. Computational mechanistic studies suggest that this advantageous behavior can be ascribed to the superior complexation of carboxylic acid anhydrides in the transition state., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Fluoroalkylations have received increasing attention in the academic and industrial environment due to the particular properties of the active ingredients that are strongly influenced by fluoroalkyl substituents. The inherent difficulties of introducing a fluoroalkyl substituent into advanced intermediates has triggered the development of an enormous number of specialized reagents, which, however, are often not suitable for large scale applications. In contrast to this reagent based fluoroalkylation approach, the direct activation of industrially readily available fluoroalkyl halides could be more suitable for a large-scale process. In this way the dithionite initiated fluoroalkylation as well as newly developed catalytically activated fluoroalkylation protocols were considered for industrial large-scale applications.

Mild and selective nickel-catalyzed trifluoromethylation and perfluoroalkylation reactions of alkenes were developed to provide fluorinated olefins, including natural products, pharmaceuticals, and variety of synthetic building blocks in good to excellent yields (38 examples). Control experiments, kinetic measurements and in situ EPR studies reveal the importance of radical species and the formation of 1,2-adducts as intermediates.

A direct perfluoroalkylation of (hetero)arenes using the air- and moisture-stable complex (dppf)Ni(o-tol)Cl was developed (23 examples). The novel procedure allows for the synthesis of various fluorinated products and tolerates sensitive functional groups including aldehydes, free amino groups and several heterocycles.

The CF3 group is an omnipresent motif found in many pharmaceuticals, agrochemicals, catalysts, materials, and industrial chemicals. Despite well-established trifluoromethylation methodologies, the straightforward and selective introduction of such groups into (hetero)arenes using available and less expensive sources is still a major challenge. In this regard, the selective synthesis of various trifluoromethyl-substituted (hetero)arenes by palladium-catalyzed C-H functionalization is herein reported. This novel methodology proceeds under comparably mild reaction conditions with good regio- and chemoselectivity. As examples, trifluoromethylations of biologically important molecules, such as melatonin, theophylline, caffeine, and pentoxifylline, are showcased., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Fluorinated organic compounds are gaining increasing interest for life science applications. The replacement of hydrogen in arenes or heteroarenes by a perfluoroalkyl group has a profound influence on the physical and biological properties of such building blocks. Here, an operationally simple protocol for the direct C-H perfluoroalkylation of (hetero)arenes with R(f)I or R(f)Br has been developed, using a robust supported platinum catalyst. The ready availability of the starting materials, the excellent substrate tolerance, and the reusability of the catalyst make this method attractive for the synthesis of a variety of perfluoroalkyl-substituted aromatic compounds. Preliminary mechanistic studies revealed the formation of radicals to be crucial in the reaction system., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The structure of the camphenyl cation 1 has been studied in detail, using both experimental and computational approaches. Like others, we find only one structure on the camphenyl-isobornyl cation PE surface, but this single structure shows some unusual features. These include a very soft PE surface for movement along the C2-C6 axis (a nonbonding distance in a classical description of the cation), and a result of this is that very high computational methods (optimization at MP4 or QCI levels) are required in order to get structural minima that "fit" the experimental data. This PE surface has been probed computationally using fixed C2-C6 distances, and when one also calculates chemical shifts for these "fixed" structures, one sees calculated (13)C NMR chemical shifts for the C2 carbon that are hugely dependent on this fixed distance value, giving near-linear slopes of ca. 25 ppm/0.1 A distance change. Since this distance can vary over at least 0.6 A with relatively small calculated energy changes, there is a total range of ca. 150 ppm involved here. In a second part of this work, and in response to a recent paper in which the historic Meerwein "carbocation intermediate" proposal was rejected, we have calculated solvation energies (SCI-PCM method) for four carbocation systems, including 1. We find carbocation solvation energies (epsilon = 10 "solvent") of 45-53 kcal/mol, and where comparison can be made, the data correlate well with the literature. On the basis of these results, we re-affirm the Meerwein "carbocation" mechanism, but in order to accommodate only a single carbocation intermediate, we offer a description that amounts to a subtle variation of both the nonclassical ion proposal and Meerwein's "two cation" mechanism, namely that the camphenyl cation, 1, as a ground-state structure, can be described as only very weakly interacting in the C2-C6 bridging sense, but that the PE surface along this "bond" is so shallow that an energy input of only 4-6 kcal/mol can produce a bridged "structure". This mechanism explains the preferred formation of exo products in both the camphenyl and isobornyl systems, isotopic exchange of chloride in camphenyl chloride, and it allows for partial racemization of the camphenyl-isobornyl products in the reaction.