Continuous Electrochemical Synthesis of Iso‐Coumarin Derivatives from o‐(1‐Alkynyl) Benzoates under Metal‐ and Oxidant‐Free

Abstract

A non‐oxidant and metal‐free strategy for synthesizing iso‐coumarin by using a continuous electrochemical microreactor to initiate an oxidative cyclization reaction of o‐(1‐alkynyl) benzoate and radicals. This efficient and clean continuous electrosynthesis method not only avoids the complicated gas protection operation and production of by‐products in the batch processes, but also help to overcome the difficulty that batch metal catalysis and electrocatalysis are difficult to scale up, and has the potential for pilot‐scale experiment.

Organic Electrosynthesis Towards Sustainability: Fundamentals and Greener Methodologies

“…Nowadays, a large number of other relevant molecules, such as heterocycles, common biological active scaffolds, are being synthesized by direct electrosyntheses. The green preparation of isocoumarin derivatives by continuous flow from o ‐(1‐alkynyl) benzoates, [51] the catalyst‐free electrosynthesis of benzimidazolones through an intramolecular oxidative C−N coupling, [52] the formation of pyrrolidines by oxidative C(sp 3 )−H amination [53] and the electrochemical C−H amidation of heteroarenes with N ‐alkyl sulfonamides in aqueous media demonstrate this fact [54] . Moreover, synthesis of higher functionalized lactones, through an anodic radical coupling pathway, has been performed recently under mild and green conditions with a wide scope of substrates [55] .…”

PhICl2-Mediated Regioselective and Electrophilic Oxythio/Selenocyanation of o-(1-Alkynyl)benzoates: Access to Biologically Active S/SeCN-Containing Isocoumarins

“…Organosulfur and selenium compounds have been widely used in organic and biological chemistry ( Parnham and Graf, 1991 ; Ip and Ganther, 1992 ; Ji et al, 1999 ; Mugesh et al, 2001 ; Yao and Larock, 2003 ; Borges et al, 2005 ; Mehta et al, 2009 ; Santos et al, 2009 ; Sperança et al, 2011 ; Wilkins et al, 2016 ; Glenadel et al, 2018 ; Lin et al, 2020 ; Mampuys et al, 2020 ). Among them, organic thiocyanated compounds and their selenylated analogs have attracted continuous attention of organic and medicinal chemists.…”

“…The chemistry that describes the preparation of 4-chalcogen isocoumain through the cyclization of 2-alkynylaryl esters promoted by electrophilic chalcogen species has been well documented ( Yao and Larock, 2003 ; Mehta et al, 2009 ; Sperança et al, 2011 ; Wilkins et al, 2016 ; Glenadel et al, 2018 ; Lin et al, 2020 ). On the other aspect, thio/selenocyanation of alkenes ( Yang et al, 2015 ; Zhang et al, 2018 ; Ye et al, 2019 ; Meng et al, 2020 ; Nadiveedhi et al, 2020 ) and hetero/aromatics ( Feng et al, 2018 ; Rezayati and Ramazani, 2020 ) has also been extensively investigated.…”

Me3SiCl‐Catalyzed Electrophilic Thiocyanation/Cyclization of Alkynylbenzoates to Synthesize 4‐Thiocyanatoisocourmarins

“…[13,14] Intramolecular cyclization of alkynylbenzoates or o-alkynyl benzoic acid is one of the most efficient and straightforward methods to construct the functionalized isocourmarins. As far, a variety of functional groups including Cl, [15] Br, [16] I, [17] CN, [18] SPh, [19] SePh, [20] TePh [21] and SCF 3 [22] have been successfully introduced into isocourmarins. It is worth mentioning that most of these reactions involve the participation of electrophiles or experience cationic intermediates, and the formation of onium ions has been speculated the key step to proceed with the functionalization of alkynes.…”