The Use of Electrophilic Cyclization for the Preparation of Condensed Heterocycles

Abstract

Condensed heterocycles are well-known for their excellent biological effects and they are undeniably important compounds in organic chemistry. Electrophilic cyclization reactions are widely used for the synthesis of mono-heterocyclic compounds. This review highlights the utility of electrophilic cyclization reactions as an effective generic tool for the synthesis of various condensed heterocycles containing functional groups that are able to undergo further chemical transformations, such as nucleophilic substitution, elimination, re-cyclization, cleavage, etc. This review describes the reactions of unsaturated derivatives of different heterocycles with various electrophilic agents (halogens, arylsulfanyl chlorides, mineral acids) resulting in annulation of an additional partially saturated heterocycle. The electrophilic reaction conditions, plausible mechanisms and the use of such transformations in organic synthesis are also discussed. The review mainly focuses on research published since 2002 in order to establish the current state of the art in this area. 1 Introduction2 Electrophilic Cyclization Pathways Involving a Nitrogen Nucleo­philic Center3 Electrophilic Cyclization Pathways Involving a Chalcogen Nucleophilic Center3.1 Sulfur Centers3.2 Oxygen Centers3.3 Selenium Centers4 Strategies and Mechanisms5 Conclusion

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

“…Then the reaction of thiocyanate with thiocyanogen chloride provides (SCN) 2 , which further reacts with the oxidative PhICl 2 to give thiocyanogen chloride ( Tao et al, 2021 ). Next, electrophilic addition between the reactive thiocyanogen chloride with substrate 1a gave rise to intermediate B ( Xing et al, 2019a ; An et al, 2020 ; Hellwig et al, 2020 ; Lynch and Scanlan, 2020 ; Sun et al, 2020 ; Jurinic et al, 2021 ; Slivka and Onysko, 2021 ). Due to the presence of the adjacent electron-withdrawing methoxycarbonyl group which makes the C (sp 2 ) connecting with the Ph substituent more electron-deficient, a favored intramolecular 6-exo cyclization occurred in intermediate B , leading to formation of the cyclic intermediate C .…”

Proton‐ and halogen‐induced cyclizations of 2‐(3‐butenyl)quinazolin‐4(3H)‐ones in the synthesis of pyrrolo[2,1‐b]‐ and pyrrolo[1,2‐а]quinazolinone derivatives

“…which is well documented in numerous review articles [75][76][77][78][79][80][81][82][83]100]. In view of extending this strategy to 2-homoallylquinazolinones 1, we have studied their reactions with common halogenating agents such as iodine, bromine, N-iodosuccinimide (NIS), and Nbromosuccinimide (NBS).…”

“…Halocyclizations of alkenyl compounds offer a powerful tool for the design of functionalized heterocycles, which is well documented in numerous review articles [75–83, 100]. In view of extending this strategy to 2‐homoallylquinazolinones 1 , we have studied their reactions with common halogenating agents such as iodine, bromine, N‐iodosuccinimide (NIS), and N‐bromosuccinimide (NBS).…”

“…Electrophilic intramolecular cyclization represents a potent synthetic strategy to construct N,O,S-containing heterocycles from the corresponding unsaturated substrates [73][74][75][76][77][78][79][80][81][82][83], and it is widely applied in the preparation of exo-functionalized polyheterocyclic systems from heteroaryl alkenes [83]. Such an approach has been recently realized for annulation and exofunctionalization of 2-alkenyl quinazolinones by bis(trifluoroacetoxy)iodobenzene (PIFA)-initiated oxidative cyclization [84] (Scheme 1A) as well as sulfenylation(selenylation)/cyclization reaction by the action of ArS(Se)Cl [85] (Scheme 1B).…”

Selective halocyclization and iodosulfonylation ofN-benzothiazol-2-yl alkynamides under mild conditions

“…This would allow for the preparation of the desired product 2 . Initially (Scheme 1d), only multisubstituted α,β-enones 4 were obtained via halosulfonylation; 10–12 however, to our delight, when the sulfonylhydrazide was removed, halocyclization 13,14 was observed, affording the pyrimidobenzothiazole 3a in 92% yield. Based on this result, we conducted the reaction in the absence of TBHP which resulted in a decrease in the yield of the desired product.…”