The intention of this review is to highlight the innovative electrolyte combination of 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) with tertiary nitrogen bases in electro-organic synthesis. This easy applicable and promising mixture is not yet well established in electro-organic synthesis, but expands the various possibilities in the latter. Combinations of fluorinated alcohols with nitrogen bases form highly conductive electrolyte systems, which can be evaporated completely. Consequently, no additional supporting electrolyte is required and work-up procedures are tremendously simplified. With this electrolyte mixture carbon-carbon homo-and cross-coupling reactions of arenes and phenols have been established with substrates that have not been previously susceptible to the anodic dehydrogenative coupling reaction. The intermediate installation of highly fluorinated alkoxy moieties can be exploited for subsequent conversions as well as various benzylic functionalization, including asymmetric transformations. These transformations show unique selectivity and functional group tolerance making them highly applicable to the synthesis of sophisticated structural motifs, including natural products.
In memory of Christoph NaethbohmUnlike common analytical techniques such as cyclic voltammetry, statistics-based optimization tools are not yet often in the toolbox of preparative organic electrochemists. In general, experimental effort is not optimally utilized because the selection of experimental conditions is based on the one-variable-at-a-time principle. We will summarize statistically motivated optimization approaches already used in the context of electroorganic synthesis. We discuss the central ideas of these optimization methods which originate from other fields of chemistry in relation to electrosynthetic applications.
Heterobiaryls consisting of a phenol and a benzofuran motif are of significant importance for pharmaceutical applications. An attractive sustainable, metal- and reagent-free, electrosynthetic, and highly efficient method, that allows access to (2-hydroxyphenyl)benzofurans is presented. Upon the electrochemical dehydrogenative C-C cross-coupling reaction, a metathesis of the benzo moiety at the benzofuran occurs. This gives rise to a substitution pattern at the hydroxyphenyl moiety which would not be compatible by a direct coupling process. The single-step protocol is easy to conduct in an undivided electrolysis cell, therefore scalable, and inherently safe.
A novel approach towards the activation of different arenes and purines including caffeine and theophylline is presented. The simple, safe and scalable electrochemical synthesis of 1,1,1,3,3,3‐hexafluoroisopropanol (HFIP) aryl ethers was conducted using an easy electrolysis setup with boron‐doped diamond (BDD) electrodes. Good yields up to 59 % were achieved. Triethylamine was used as a base as it forms a highly conductive media with HFIP, making additional supporting electrolytes superfluous. The synthesis was optimized using Design of Experiment (DoE) techniques giving a detailed insight to the significance of the reaction parameters. The mechanism was investigated by cyclic voltammetry (CV). Subsequent transition metal‐catalyzed as well as metal‐free functionalization led to interesting motifs in excellent yields up to 94 %.
Invited for this month's cover picture is the group of Siegfried R. Waldvogel at Johannes Gutenberg‐University in Mainz accompanied by Jonny Proppe at Georg‐August University in Göttingen. The cover picture shows three schemes illustrating the methods Principal Component Analysis, Machine Learning, and Design of Experiment as a representative of statistical methods to be used for optimization in electroorganic synthesis. The green power plug highlights the great potential of the combination of electrochemistry with these methods to propel the field to a highly sustainable future. All of the elements are backed with the contour plot of a mathematic model. Read the full text of the Minireview at 10.1002/celc.202100318.
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