| dc.description.abstract | Arynes are highly reactive electrophilic intermediates, extensively used for synthesizing various benzo-fused heterocycles and 1,2-disubstituted benzenes. Among the numerous reactions of arynes, multicomponent coupling (MCC) has been widely used to synthesize versatile and structurally complex 1,2-disubstituted benzenes. In a conventional aryne MCC, the nucleophile having no acidic hydrogen adds to the highly electrophilic aryne generating the aryl anion intermediate, which is subsequently intercepted by the electrophile to furnish 1,2-disubstituted arenes. In this context, Mr. Subrata Bhattacharjee has demonstrated the synthetic potential of KI as the nucleophilic iodide source in aryne three-component coupling using aldehydes as the third component. This mild and transition-metal-free coupling reaction allowed the straightforward synthesis of 2-iodobenzyl alcohols in moderate to good yields with good functional group compatibility. Mr. Subrata could also use KBr and KCl as the nucleophilic trigger and N-methylisatin and CO2 as the electrophilic third components in this aryne multicomponent coupling (MCC).
In the vast realm of transition-metal-free aryne MCCs, only aprotic nucleophiles are employed as triggers, and the use of protic nucleophiles is not demonstrated. This is because, in many cases, the use of protic nucleophiles leads to the protonation of the generated aryl anion intermediates leading to the arylation. In this line, Mr. Bhattacharjee has employed thiophenols as a protic nucleophilic trigger in the transition-metal-free and Grignard reagent-free three-component coupling involving arynes. Employing aldehydes as the third component, the reaction allowed the mild and broad scope synthesis of 2-arylthio benzyl alcohol derivatives in good yields. Moreover, Mr. Subrata has extended the reaction to selenophenol as the nucleophilic trigger, and activated ketones as the third component.
Mr. Bhattacharjee has also synthesised biologically important S-aryl dithiocarbamates by the aryne three component coupling involving CS2 and aliphatic amines. This transition-metal-free and mild reaction is scalable and operates with good functional group compatibility. Contrary to the known aryne MCCs involving amines and CO2, this reaction proceeds via the initial addition of amines to CS2 followed by the trapping with arynes to furnish the desired products. Mr. Bhattacharjee has presented detailed experiments and DFT studies to get insight into the mode of addition and product formation. Moreover, using 3-triflyloxybenzyne, a four-component coupling with the incorporation of THF was also presented.
The aryne ene reaction, although well-known, has not enjoyed widespread use in synthesis, primarily because of poor selectivity and low yields due to the competing [4+2], [2+2] pathways. However, the emergence of contemporary methods to generate arynes under mild conditions has led to significant advancements in the aryne ene reaction. Over the past two decades, a significant number of efficient and selective processes have been described, employing a wide range of substrates, including alkenes, alkynes, allenes etc. In this context, Mr. Bhattacharjee have demonstrated a unique strain-release ene reaction bicyclo[1.1.0]butanes (BCBs) employing arynes by utilizing the substantial π-character of the strained central C–C bond of the BCBs. The ene reaction proceeds under mild conditions and results in the formation of substituted cyclobutene derivatives in excellent yields. | en_US |
