Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - e-Cat (The Electron as a Catalyst)

Teaser

Is the electron a catalyst in synthesis? This fundamental question will be addressed. In the challenging project, e-catalysis and its potential in synthesis will be investigated. The aim is to establish e-catalysis as an independent research branch in organic synthesis. The...

Summary

Is the electron a catalyst in synthesis? This fundamental question will be addressed. In the challenging project, e-catalysis and its potential in synthesis will be investigated. The aim is to establish e-catalysis as an independent research branch in organic synthesis. The generality and broad applicability of the concept has to be documented. Different reactions, which are currently conducted as non-chain reactions by using transition metals as redox catalysts, will be performed via electron-catalyzed radical chain processes. In view of the foreseen shortage of transition metals we consider the development of transition-metal-free chemistry as important. Preparative and kinetic experimental studies will be supported by theoretical chemistry.

Work performed

So far, we have published 23 papers. One research line was devoted to the use of alcoholates as radical chain reducing reagents. Various aryl iodides and bromides are efficiently reduced by Na-alcoholates. The alpha-H-atom in Na-alcoholates is activated by around 14 kcal/mol as compared to the parent alcohols. H-atom transfer from the weak C-H bond in such Na-alcoholates to the aryl radical results in ketyl radical anions, that act as SET-reductants. The strong sigma-bond activation in anionic radicals have served as the basis for development of e-catalyzed alkenyl- and alkynyl-migrations. We also used ethereal solvents as radical chain reductants under basic conditions for the reduction of various aryl halides. Electrochemical studies have been conducted along those lines and individual steps in these cascades were calculated using DFT methods. Hence, aryl bromides and even less activated aryl chlorides could be reduced via this e-catalyzed process.
Along with the iodides that we often use to initiate e-catalyzed radical reactions, we also studied the electrochemical approach to initiate an e-catalyzed phenanthridine synthesis. This allowed for the estimation of a turnover number of an e-catalyzed process. Regarding initiation of e-cat-processes, we also investigated the thermal homolysis of deprotonated pinacols to give the corresponding ketyl radical anions and in collaboration with Prof. Chechik (York) we successfully used non-thermal plasma for initiation of an electron-catalyzed heteroarene synthesis.
The acidity of radical anions has been in focus throughout the first project period and in collaboration with Dr. Mück-Lichtenfeld (Münster) we gathered data using the theoretical approach. We also investigated novel heteroarene syntheses applying the concept of electron-catalysis and hydrazones were found to be valuable radical acceptors for electron-catalyzed transformations. Often perfluoroalkyl iodides, that are readily SET-reduced by organic radical anions occurring as intermediates in electron-catalyzed transformations, have been used as C-radical precursors. We also established electron-catalyzed α-perfluoroalkyl-β-heteroarylation of various alkenes with perfluoroalkyl iodides using quinoxalin-2(1H)-ones as radical acceptors. For less reducing radical anions, we found that I(III)-reagents showing a higher reduction potential than perfluoroalkyl iodides are valuable radical precursors. For example, the I(III)-chemistry was successfully applied to the regio- and stereoselective radical perfluoroalkyltriflation of alkynes using phenyl(perfluoroalkyl)iodonium triflates as the C-radical precursors. Moreover, a metal-free direct alkene-C-H cyanation was developed using I(III)-chemistry. Alkynyl-I(III)-species were also used as C-radical trapping reagents of redox-catalyzed alkene amidoalkynylation reactions. To this end, a novel amidyl radical precursor that allows generating an N-radical upon single electron oxidation was developed. This N-radical precursor was successfully used in a hole-catalyzed alkene amidofluorination reaction.
In 2017, we introduced alkenyl boron ate complexes as highly valuable radical acceptors in electron-catalyzed radical-polar crossover reactions. This approach was later extended towards the preparation of α-chiral ketones and also dienyl boron-ate complexes engage in electron-catalyzed radical functionalization to provide valuable allyl boronic esters. We also used the boron-ate radical chemistry in alkaloid synthesis and developed a mild radical protocol for the hydrodeboronation of primary alkyl boron ate complexes. Boron-ate complexes were also used in transition-metal free direct C-H alpha-arylation or alpha-alkylation reactions using a conceptually novel C-C coupling strategy. In addition, catechol diborane was found to be a highly efficient alkyl radical borylation reagent in the presence of Lewis-basic solvents. For example, mild electron-catalyzed alkene 1,2-perfluoroalkylborylat

Final results

With the boron-ate complexes we introduced highly valuable unconvential radical acceptors that show great potential in radical chemistry. The boron-based radical acceptor allowed for the development of new radical methodology, significantly expanding the chemical space of free radical chemistry. In our radical ionic crossover sequence, the valuable boronic ester entity remains in the product.The potential of the radical ionic cross over methodology was documented by the development of straightforward methods for the preparation of gamma-lactones and alpha-chiral ketones. In our latest work in this boron-field, a novel alpha-C-C coupling reaction of boronic esters has been developed. This coupling method is complementary to existing methodology and does not require any transition-metal catalysis. Again, boron-ate complexes turned out to be highly valuable starting materials.
Radical dehalogenations in aryl halides have been conducted mainly using toxic tin hydrides. We have shown that such transformations can readily be achieved with simple and cheap alcoholates. With the electrochemical initiation we introduced a promising and unconventional method for the initiation of an electron-catalyzed transformation. Importantly, upon measuring the current consumption we can estimate the turnover number of our electron-catalyzed processes. On a single example we have successfully followed that strategy. In addition, we also used a Helium plasma to initiate electron-catalyzed cascades. This work has been done in collaboration with Prof. V. Chechik in York. No doubt, the use of a plasma to conduct radical chemistry is unconventional, represents novel methodology and we see potential along those lines.
The radical borylation with catechol diboranes (B2cat2) also represents a highly valuable method. Borylation of alkyl and aryl iodides is highly practical and should find use in industry. In most projects investigated, we have used DFT-calculations to support our mechanistic proposals.

Website & more info

More info: https://www.uni-muenster.de/Chemie.oc/studer/.