Gerald Pratsch

Radical Arylation of Phenols, Phenyl Ethers, and Furans

Radical arylations of para-substituted phenols and phenyl ethers proceeded with good regioselectivity at the ortho position with respect to the hydroxy or alkoxy group. The reactions were conducted with arenediazonium salts as the aryl radical source, titanium(III) chloride as the reductant, and diluted hydrochloric acid as the solvent. Substituted biaryls were obtained from hydroxy- and alkoxy-substituted benzylamines, phenethylamines, and aromatic amino acids. The methodology described offers a fast, efficient, and cost-effective new access to diversely functionalized biphenyl alcohols and ethers. Free phenolic hydroxy groups, aromatic and aliphatic amines, as well as amino acid substructures, are well tolerated. Two examples for the applicability of the methodology are the partial synthesis of a beta-secretase inhibitor and the synthesis of a calcium-channel modulator.

The Gomberg-Bachmann reaction for the arylation of anilines with aryl diazotates.

Simply aqueous sodium hydroxide is sufficient to exclude ionic side reactions and to prepare 2-aminobiphenyls from aryl diazotates and anilines through a new variant of the Gomberg-Bachmann reaction (see scheme). The metal-free reaction under basic conditions allows to exploit the highly radical-stabilizing effect of the anilines free amino function for the first time, which leads to a so far unreached regioselectivity.

Hydroxy‐ and Aminophenyl Radicals from Arenediazonium Salts

Arenediazonium salts and their synthetic applications have a long history in both ionic and radical chemistry. Starting with the pioneering work by Peter Griess in the 1860s, arenediazonium salts became well-known through several prominent name reactions among which the Sandmeyer, Meerwein, Pschorr, Gomberg-Bachmann, and the Japp-Klingemann transformations. Given the large number of reports published in this field in the past 150 years, it is surprising that there is one group of diazonium ions for which radical reactions remained practically unknown. Driven by the interest to find out whether this exclusion is due to the unique reactivity of the hydroxy-substituted aryl radicals 1 and 2, or is rather a consequence of special properties of the related arenediazonium ions 3 and 4 (e.g., the possible formation of quinonediazides), we revisited the chemistry of these compounds and their reactive intermediates. Herein, we summarized our first results.

Modern Developments in Aryl Radical Chemistry

This review summarizes recent advances in the field of aryl radical chemistry. In particular, modern developments of the well-known Meerwein, Pschorr, and Gomberg-Bachmann reactions are presented along with new applications in natural product syntheses. Among the methods for the generation of aryl radicals, tin hydrides play a predominant role, but more and more attractive and promising alternatives are beginning to emerge.

The Trapping of Phenyldiazenes in Cycloaddition Reactions

The reactivity of phenyldiazenes was studied intensively in the late 1960s, but not much is known about their behavior under acidic conditions. Based on the formation of phenyldiazenes from phenylazocarboxylates, we herein describe how reactions of phenyldiazenes can be directed into ionic or radical pathways. Cycloaddition reactions with furans leading to pyridazinium salts represent the first examples for the direct trapping of phenyldiazenes with conservation of the N=N moiety.