Synthesis of Benzothiophene Derivatives by Pd-Catalyzed or Radical-Promoted Heterocyclodehydration of 1-(2-Mercaptophenyl)-2-yn-1-ols

Abstract

Novel and convenient approaches to benzothiophene derivatives 3 and 5 have been developed, based on heterocyclization reactions of 1-(2-mercaptophenyl)-2-yn-1-ols 2 or 4, respectively, readily available from alkynylation of 2-mercaptobenzaldehydes or 1-(2-mercaptophenyl) ketones 1. In particular, 1-(2-mercaptophenyl)-2-yn-1-ols 2, bearing a CH(2)R substituent on the triple bond (R = alkyl, aryl), were conveniently converted in fair to good yields (55-82%) into (E)-2-(1-alkenyl)benzothiophenes 3 when allowed to react in the presence of catalytic amounts (2 mol %) of PdI(2) in conjunction with KI (KI:PdI(2) molar ratio =10) at 80-100 °C in MeCN as the solvent, through a heterocyclodehydration process. On the other hand, 2-alkoxymethylbenzothiophenes 5 were selectively obtained in fair to excellent yields (49-98%) via a radical-promoted substitutive heterocyclodehydration process, by reacting 1-(2-mercaptophenyl)-2-yn-1-ols 4 (bearing an alkyl or aryl substituent on the triple bond) in alcoholic media at 80-100 °C in the presence of a radical initiator, such as AIBN.

Synthesis and functionalization of 3-bromo-2-(2-chlorovinyl)benzothiophenes as molecular tools

“…Next, we continued our study by exploring the inuence of the palladium-and ligand-controlled site-selective SuzukiMiyaura cross couplings. No reaction occurred by replacing Pd(PPh 3 ) 4 with other palladium sources such as PdCl 2 (PPh 3 ) 2 , PdCl 2 (dppf) and Pd(dba) 2 (entries 2-4), even when increasing the amount of the catalyst from 5 to 20 mol%. By using the N-heterocyclic carbene palladacycle precatalyst [PdCl(dmba)(IMes)] (Pd-NHC) developed in 2008 by Ying 16 for Heck-and Suzuki-coupling reactions, we were pleased to observe the formation of the desired C-3 monoarylated benzothiophene (E)-8a in a moderate but promising yield of 38% aer 7 h of reaction (entry 5).…”

“…To our knowledge, these derivatives having (E)-double bonds have been prepared using three different strategies: (i) the Pdcatalyzed heterocyclodehydration of acyclic precursor 2, 4 (ii) reaction of 3 with LDA followed by rearrangement in the presence of ZnBr 2 , 5 and (iii) C3-functionalization of 2-substituted benzothiophene 4 through a three-step sequence involving a Rieche formylation, a Wittig reaction, and a pyrrole ring construction under van Leusen reaction conditions. 6 In a continuation of our work dedicated to the synthesis of functionalized heterocycles, 7 we described a new method to prepare a variety of stereo-dened polyhalogenated platforms 6 through the N-methyl-pyrrolidin-2-one hydrotribromide (MPHT)-promoted bromocyclization of (Z)-and (E)-chloroenynes 5 and subsequent site-selective Suzuki-Miyaura coupling reactions of 6 to prepare various 2,3-disubstituted benzothiophenes 1 (Scheme 2).…”

Synthesis of 2‐Acylselenophenes via Iodine‐Promoted Nucleophilic Cyclization of [2‐(Butylselanyl)phenyl]‐propynols

“…The nucleophilic aromatic substitution reactions of 2‐halobenzaldehydes with lithium butylselenolate afforded the aryl butyl selenides 1 in 63–75% yields. The alkynylation of selenides 1 with lithium acetylides gave [2‐(butylselanyl)phenyl]propynols 2 34. All details for the preparation of [2‐(butylselanyl)phenyl]propynols 2 are presented in Table 1.…”

Recent developments in synthetic methods for benzo[b]heteroles

“…Gabriele and coworkers utilized similar substrates featuring a free SH group to achieve palladiumcatalyzed and radical-mediated 5-exo-cyclizations leading to benzothiophenes. 70 Scheme 30 Annulation of ortho-methylthio-and methylselenoaryldiazonium salts with alkynes. Recently, Procter and coworkers have significantly expanded the scope and utility of the 5-exo cyclization approach to benzothiophenes (Scheme 34a).…”