The Gomberg–Bachmann Reaction for the Arylation of Anilines with Aryl Diazotates

Abstract

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 aniline's free amino function for the first time, which leads to a so far unreached regioselectivity.

Synthetic journey towards transition metal-free arylations

“…Pratsh et al [55] discussed the radical-mediated a-arylation anilines with aryl diazotates salt by easily accessible TMF conditions. The protocol scenario involved the reactions of anilines and aryl diazotates in the presence of NaOH/H 2 O to form corresponding o-arylated anilines 88 within the range of 43-68 % yields.The reaction conditions involved mild, simple and scalable conditions (Scheme 29).…”

Radical Arylation of Anilines and Pyrroles via Aryldiazotates

“…[19] After severalv ariations,aprocedure that provided aryldiazotate 2a as ac lear,a lmost colorless aqueous solution was established. [19] After severalv ariations,aprocedure that provided aryldiazotate 2a as ac lear,a lmost colorless aqueous solution was established.…”

“…[28] With the optimized conditions now available, we reevaluated the synthesis of as election of 2-aminobiphenyls 4.A comparison between the yields obtained from the previous protocol [19] and the newly developed procedure is summarized in Table 3. In less successful attempts, precipitate formation and the emergence of ay ellow color indicated the formation of undesired side products,s uch as diazo anhydrides.…”

“…Known examples are arylazo sulfides, [18] which can even enabler adical arylation of strongly nucleophilic phenolates.The arylationof anilines was unreported under metal-free, basic Gomberg-Bachmann type conditions for al ong time,b ut has recently been achieved with aryldiazotates. [19,20] In comparisont oa ryldiazo anhydrides, which are the generally accepted intermediates in classical Gomberg-Bachmann reactions, [21] aryldiazotates show am uch greater stabilityt owards nucleophilic attack. [22] Also, very recently, ortho-selective arylation of anilinesv ia benzyne intermediates has been reported by Truong and Daugulis.…”

How the Structural Elucidation of the Natural Product Stephanosporin Led to New Developments in Aryl Radical and Medicinal Chemistry

“…118 In all cases, however, only small amounts of the desired 2-aminobiphenyls were isolated, and azo coupling and triazene formation were identified as the predominant pathways. We therefore concluded that diazo anhydrides [for example, 2,2′-oxybis(phenyldiazene)], which Rüchardt and Merz proposed as key intermediates in the Gomberg-Bachmann reaction, 119 are insufficiently protected forms of diazonium ions to suppress the ionic pathways.…”