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Electrosynthesis 2.0 in 1,1,1,3,3,3‐Hexafluoroisopropanol/Amine Mixtures

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Electrosynthesis 2.0 in 1,1,1,3,3,3‐Hexafluoroisopropanol/Amine Mixtures Reviews ChemElectroChem doi.org/10.1002/celc.202000761 1 2 3 Electrosynthesis 2.0 in 1,1,1,3,3,3- 4 5 Hexafluoroisopropanol/Amine Mixtures 6 [a, b] [a] [a, b] 7 Johannes L. Röckl, Maurice Dörr, and Siegfried R. Waldvogel* 8 In memory of Prof. Dr. Dennis G. Peters 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 ChemElectroChem 2020, 7, 3686–3694 3686 © 2020 The Authors. Published by Wiley-VCH GmbH Wiley VCH Dienstag, 15.09.2020 2018 / 172424 [S. 3686/3694] 1 Reviews ChemElectroChem doi.org/10.1002/celc.202000761 1 The intention of this review is to highlight the innovative mixture carbon-carbon homo- and cross-coupling reactions of 2 electrolyte combination of 1,1,1,3,3,3-hexafluoroisopropanol arenes and phenols have been established with substrates that 3 (HFIP) with tertiary nitrogen bases in electro-organic synthesis. have not been previously susceptible to the anodic dehydro- 4 This easy applicable and promising mixture is not yet well genative coupling reaction. The intermediate installation of 5 established in electro-organic synthesis, but expands the highly fluorinated alkoxy moieties can be exploited for subse- 6 various possibilities in the latter. Combinations of fluorinated quent conversions as well as various benzylic functionalization, 7 alcohols with nitrogen bases form highly conductive electrolyte including asymmetric transformations. These transformations 8 systems, which can be evaporated completely. Consequently, show unique selectivity and functional group tolerance making 9 no additional supporting electrolyte is required and work-up them highly applicable to the synthesis of sophisticated 10 procedures are tremendously simplified. With this electrolyte structural motifs, including natural products. 11 12 1. Introduction degree.[26] The melting point is À 4 °C,[27] and HFIP has a high 13 density of 1.517 g/mL while being miscible with water and 14 Fluorinated alcohols have emerged as excellent choices for a most organic solvents.[24] 15 broad range of applications in organic chemistry, due to their Electrochemistry has experienced a renaissance in recent 16 high hydrogen-bond donor ability,[1,2] high polarity,[2,3] outstand- years since it offers benefits over classical synthetic 17 ing (electro-)chemical stability,[4,5] and micro-heterogeneity.[6–8] methodologies.[18–20,28] Electric current, as an inexpensive and 18 This is illustrated by their use as solvents, co-solvents or inherently safe reagent, facilitates sustainable synthetic path- 19 promoters in organic syntheses.[2,5,9,10] Several examples have ways, and is compatible with renewable energy sources.[29] A 20 showcased the utility of 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) direct contribution for the stabilizing of the electric grid is 21 in transition metal-catalyzed,[10,11] and metal-free reactions.[12] In provided, when the electro-conversions are robust and fluctuat- 22 combination with bases, HFIP promotes unusual transforma- ing electricity can be employed without loss of selectivity and 23 tions like the generation of aza-oxyallyl cationic intermediates reactivity. Here, HFIP based electrolytes seem to play an 24 from α-haloamides[13] or HFIP-promoted nucleophilic outstanding role.[30] The avoidance of chemical reagents mini- 25 substitutions[9,14]. These unique features of HFIP make it mizes the amount of reagent waste produced by the process. 26 particularly well-suited as a solvent for electrochemical reac- Thus, many of the “green chemistry” principles may be fulfilled 27 tions, especially its ability to stabilize radical intermediates.[15,16] by applying electro-organic methods.[30,31] A common drawback 28 HFIP has demonstrated superior effects compared to other in electrochemistry is the need for supporting electrolytes, 29 solvents when it comes to improving selectivity and yield of which are often salts with significant environmental impact.[32] 30 various electrochemical transformations.[17–21] In particular, the The subsequent workup is complicated due to difficult removal 31 solvate formation modulates nucleophilicity and oxidation or recovery of the salt. Noteworthy, perchlorates can lead to 32 potential.[7,17] The unusual electrochemical stability of HFIP is explosive events and symmetric tetraalkylammonium salts 33 ensured as long as inert anodes are employed for direct strongly affect the wastewater treatment.[33] When applying a 34 electrode processes,[22] whereas hypervalent iodine mediators combination of base with acidic HFIP (pK =9.3[15]) to electro- 35 a are capable to convert HFIP to highly toxic organic synthesis, a supporting electrolyte is formed in-situ, 36 hexafluoroacetone.[23] HFIP is corrosive and a strong skin and eliminating the need for additional supporting electrolyte. 37 respiratory irritant, but nevertheless easy to handle.[24] For a Avoiding the use of salts simplifies the workup procedure, 38 long time the biggest drawback of HFIP was its comparably facilitating easy removal of the electrolyte by distillation, 39 high costs for a solvent. In past decades, general anesthesia, simplifying downstream processing and recycling of the electro- 40 e.g. sevoflurane, became common in use, wherein HFIP is a lyte. Additionally, the lack of salts allows the coupling with 41 synthetic precursor. Typical cost range from a 100 to 300 euros mass spectrometry for real-time reaction monitoring in, for 42 per kg and highly depend on the scale being bought.[25] Due to example, automated synthesis. In addition, the enhanced 43 the low boiling point of 58 °C the recovery of HFIP by distillation nucleophilicity of deprotonated HFIP allows trapping of reactive 44 is simple, thus overcoming the significant costs to a certain intermediates, which can be submitted to different coupling 45 reactions to open new pathways in organic synthesis. For 46 [a] J. L. Röckl, M. Dörr, Prof. Dr. S. R. Waldvogel example, in 2013 Tajima et al. first described the use of a solid- 47 Department of Chemistry supported base in HFIP in a one-pot sequence of alkoxylation 48 Johannes Gutenberg University Mainz followed by the reaction with allyltrimethylsilane (Scheme 1).[34] 49 Duesbergweg 10–14, 55128 Mainz (Germany) E-mail: [email protected] Subsequently, our group first used a simple tertiary amine base 50 Homepage: https://www.aksw.uni-mainz.de without additional salt or reagents in a formal benzyl-aryl cross- 51 [b] J. L. Röckl, Prof. Dr. S. R. Waldvogel coupling reaction, demonstrating the potential of this approach 52 Graduate School Materials Science in Mainz (Scheme 3).[35] Many more seminal applications of this powerful 53 Staudingerweg 9, 55128 Mainz (Germany) © 2020 The Authors. Published by Wiley-VCH GmbH. This is an open access combination have been recently published and will be 54 article under the terms of the Creative Commons Attribution Non- discussed within this review.[36–40] 55 Commercial NoDerivs License, which permits use and distribution in any 56 medium, provided the original work is properly cited, the use is non- commercial and no modifications or adaptations are made. 57 ChemElectroChem 2020, 7, 3686–3694 www.chemelectrochem.org 3687 © 2020 The Authors. Published by Wiley-VCH GmbH Wiley VCH Dienstag, 15.09.2020 2018 / 172424 [S. 3687/3694] 1 Reviews ChemElectroChem doi.org/10.1002/celc.202000761 1 2 3 4 5 6 7 8 9 10 Scheme 1. One-pot sequence enabling allyl-substituted lactams utilizing a 11 solid-supported amine base in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP). 12 13 14 2. Anodic Alkoxylation Promoted by 15 Solid-Supported Base as Part of a One-Pot 16 Sequence 17 Scheme 2. Electro-organic access to phenanthridines and related structures using 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) and ammonia. 18 The Tateno group developed an elegant anodic alkoxylation of 19 lactams followed by allylation in a one-pot sequence using HFIP 20 in combination with a solid-supported amine base.[34] This gives 21 rise to allylated five- and six-membered lactams (1) and (2) in 3. Electro-organic Formation of Nitrogen 22 yields up to 82% over both steps (Scheme 1). After electrolysis Heterocycles using Ammonia in HFIP 23 the silica-supported piperidine can be easily removed by 24 filtration. In case of a 7-membered ring (3) the intermediate N- The ubiquity of nitrogen moieties in natural products, pharma- 25 acyliminium ion was not formed and therefore no reaction took ceutically active compounds, and advanced materials highlights 26 place. the necessity for sustainable formation of nitrogen 27 heterocycles.[41] Several approaches have been described along 28 with electro-organic CÀ N bond construction.[42] A regioselective 29 30 31 Johannes L. Röckl finished his apprenticeship Siegfried R. Waldvogel studied chemistry in 32 as a laboratory technician in 2013 at BASF SE, Konstanz (Germany) and received his Ph.D. in 33 Ludwigshafen (Germany) and received his 1996 from University of Bochum/Max Planck 34 B.Sc. from Johannes Gutenberg University Institute for Coal Research (Germany) with 35 (Germany) in a collaboration with BASF SE Prof. Dr. M. T. Reetz as supervisor. After post- 36 working on the total synthesis of natural doctoral research at Scripps Research Institute 37 product derivatives under supervision of in La Jolla, CA (USA) with Prof. Dr. J. Rebek, Jr., Prof. Dr. Siegfried R. Waldvogel and Dr. Joa- he started his own research career in 1998 at 38 chim Dickhaut in 2016. Afterwards, he was University of Münster (Germany). After his 39 appointed as a scientist in insecticide science professorship in 2004 at University of Bonn 40 working on early stage projects for BASF. (Germany), he became full professor for 41 Upon acceptance as a fast-track Ph.D.
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