The Trapping of Phenyldiazenes in Cycloaddition Reactions

Abstract

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.

Radical Carbofluorination of Alkenes with Arylhydrazines and Selectfluor: Additives, Mechanistic Pathways, and Polar Effects

“…A slight improvement was achieved through incomplete degassing, which leaves traces of oxygen in the reaction mixture (entry 5). This effect can be rationalized by the facilitated generation of aryl radicals from 5 a , because oxygen readily decomposes phenyldiazene (ArN=NH), which occurs as an intermediate . Although the optimized conditions of entry 5 did not allow to decrease the amount of Selectfluor ( 2 ) to three equivalents (entry 6), lower amounts of the alkene (entry 7) and a faster addition of 5 a over 30 minutes (entry 8) were tolerated with an only minor drop in yield.…”

“…Starting from phenylhydrazine 5,o xidation by Selectfluor (2)a tf irst provides phenyldiazene 22 [step (A)].T he formation of 22 under the typical carbofluorination conditions could be confirmed through trapping of 22 b with 2,5-dimethylfuran ( 23), which led to the pyridazinium salt 24 b in 51 % yield (Scheme 7). [19] Thef urther oxidation of 22 to 9 under loss of dinitrogen represents one of the critical steps in the carbofluorination [step (B), Scheme 6],b ecause it is greatlyf acilitated by the presence of dioxygen, [19] but al arge amount of dioxygen would later on promote the undesired formationofhydroperoxide 25 from 8 [step (E)]. [12a, 23] This background thus explainsw hy partial degassing, so that al imited but defined amount of dioxygen is available,w as beneficial.…”

“…In the absence of anisole (12), 3 does readily attack alkene 6 to give 28 [step (H)] (Scheme 6). Interestingly,a lkyl radical 28 is then almoste xclusively trapped by 22 or 26 to give 19 [step (I)], but not by Selectfluor (2)t op rovide 29 [step (J)],b ecause 29 could not be detected among the hydrophilic productsb y 19 FNMR spectroscopy or LC-MS. Given that the two secondary alkyl radicals 8 and 28 should possess ac omparable reactivity, but 8 preferably reacts with 2 to give 7 [step (D)],w hereas 28 chooses 22 or 26 to give 19 [step (I)],wea ssume that as trong polar effect (lipophilic phenyl group in 8 versusd oubly chargedd iazabicycle in 28)i sr esponsible for this remarkable selectivity.A tt his point, it is worth to mention that the direct attack of radicald ication 3 onto an alkene has so far not been reported;h ence,t his observation could be an interesting starting point forfuture developments.…”

Microwave‐Assisted Rapid One‐Pot Synthesis of Fused and Non‐Fused Indoles and 5‐[18F]Fluoroindoles from Phenylazocarboxylates

“…This particular step required a more extensive optimization, since the zinc powder remaining from the first stage could, in combination with the large excess of hydrochloric acid required in the second stage, as well lead to a reduction of 4‐fluorophenylhydrazine 6 to 4‐fluoroaniline ( 7 ) (Scheme ) . On the other hand, and assuming that zinc was fully consumed during the formation of 6 (e.g., through formation of dihydrogen), an air‐promoted oxidation of 6 to 4‐fluorophenyldiazene ( 8 ) might occur, which would ultimately result in the formation of fluorobenzene ( 9 ) via a radical pathway . In addition, a decomposition of the desired product 4 a under the strongly acidic conditions could not be excluded at this initial stage.…”

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

“…From these observations, we developed the first trapping reaction of phenyldiazenes (Scheme 37). 133 Cycloadditions of phenyldiazenes, generated in situ from the corresponding azocarboxylate salts, to furans gave pyridazinium salts in up to quantitative yields. For example, the pyridazinium salt 127 was prepared from azocarboxylate 124 and 2,5-dimethylfuran (128) through formation of 4-fluorophenyldiazene (129) in situ.…”