Iodine/Water‐Mediated Oxidation of o‐Alkynylaroyl Compounds and Application of the Products of Oxidation in the Synthesis of Nitrogen Heterocycles

Abstract

A facile iodine/water‐mediated oxidation of the triple bond of o‐alkynylaroyl compounds to furnish tricarbonyl compounds is reported. The reaction proceeds through the formation of isochromenol intermediates by the assistance of the neighbouring aroyl group. The product tricarbonyl compounds are versatile synthetic precursors that, upon treatment with mono‐ and diamines, hydrazines and amino alcohols, afford various heterocyclic scaffolds such as isoindolinones, phthalazines, benzimidazoisoquinolinones, quinoxalines and benzimidazole‐quinoxaline hybrid compounds. Mechanistic aspects of the formation of the above heterocycles are discussed. Finally, a short synthetic route to the isoindolinone natural product, aristolactam BII is reported.

The α,α‐Dihalocarbonyl Building Blocks: An Avenue for New Reaction Development in Organic Synthesis

“…Later, the same research group, extended their methodology to o ‐alkynylarene ketone derivatives 178 . Iodine‐mediated, carbonyl directed diiodenative‐oxidation reaction was found to be very general for the synthesis of tricarbonyl compounds 177 , with good to excellent yields.…”

Synthesis of Substituted Benzils from Diarylalkyne Oxidation

“…The use of I 2 in alcohols/MeCN or water/MeCN has been investigated by Srinivasan and Sakthivel. 13,14 The oxidation of diarylalkynes bearing an aldehyde function in the ortho position of the aromatic ring 13 using I 2 (2.1 equiv) in H 2 O/MeCN at room temperature, the oxidizing process occurred well with electron-rich or electron-poor diarylalkynes to furnish the desired benzils (entries 8 and 9). A plausible mechanism is proposed in which the ortho-aldehyde group acts as a neighboring assistant during the oxidizing process (Scheme 2).…”

“…This reacts with a second equivalent of I 2 to give a diiodoketo-aldehyde of type II which undergoes displacement of iodine atoms with H 2 O. It is also possible to use these experimental conditions with diarylalkynes with a keto group in the ortho position (entries [11][12][13][14].…”

“…When replacing the ortho-formyl or ortho-keto function by an ester group, the 4-iodoisocoumarin is formed as the sole product with no trace of any benzil derivatives. 14 A comparative study between the use of I 2 or PhSeSePh in the presence of [bis(trifluoroacetoxy)iodo]benzene (PIFA) for the conversion of diarylalkynes into benzils showed that I 2 seems to be less effective than PhSeSePh as the co-oxidizing species. 15 Some selected examples are reported in Scheme 3.…”

“…lytic systems were efficient with electron-rich (entries 1-10) or electron-poor arylalkynes (entries [11][12][13][14][15][16][17][18][19][20], as well as with push-pull and pull-pull diarylalkynes (entries [21][22][23][24][25][26][27].…”