Cyclization of Diaryl(hetaryl)alkynes under Selenobromination Conditions: Regioselectivity and Mechanistic Studies

Abstract

The cyclization of substituted diaryl(hetaryl)alkynes with in‐situ‐prepared SeBr4 has been achieved. The use of an alkene additive as a bromine scavenger gives simple access to functionalized benzo[b]selenophene and selenophenothiophene derivatives from commercially available or easily accessible starting materials. The reactions can be performed in air without the use of moisture‐sensitive reagents, dry solvents, or an inert atmosphere. Mechanistic studies confirmed a regioselective anti 1,2‐addition in the selenobromination step, and a subsequent electrophilic substitution in the aromatic ring to complete the cyclization.

Natural‐Antioxidant‐Inspired Benzo[b]selenophenes: Synthesis, Redox Properties, and Antiproliferative Activity

“…was used in the synthesis of the core structure of raloxifene. [8] By taking the advantages of both methods (Scheme 1), we overcamet he regioselectivity issues that faced the direct cyclization of diarylalkynes, [9] thereby providing ag eneral approach for the synthesis of the desired functionalized 2-and 3-arylbenzo[b]selenophenes.…”

Recent Advances in the Synthesis of Selenophenes and Their Derivatives

“…The aldehyde 104c, however, afforded the respective product 105c in only 11% yield, while the TMS-protected alkyne 104d generated the deprotected benzoselenophene 105d, in 44% yield, which was desilylated in situ by the addition of TBAF (0.5 equi) in the reaction medium (Scheme 70). In the following year (2015), additional outcomes on the SeO2-mediated cyclization of type E precursors were described (Scheme 71) [165]. The authors used different symmetrical and unsymmetrical diarylalkynes 106, demonstrating the strong influence of different substituents attached to the aromatic ring.…”

“…In this case, the bromination of the C-C triple bond was not observed; however, the transformation showed a poor regioselectivity, leading to the formation of both possible regioisomers and an inseparable mixture of compounds (Scheme 71, compound 107j). In the following year (2015), additional outcomes on the SeO 2 -mediated cyclization of type E precursors were described (Scheme 71) [165]. The authors used different symmetrical and unsymmetrical diarylalkynes 106, demonstrating the strong influence of different substituents attached to the aromatic ring.…”

“…The selenopheno [2,3-b]thiophenes 162f and 162g were obtained in 56% and 39% yields, respectively, while the diphenyl-substituted selenophene (162h) was not formed, reinforcing the influence of steric effects in the reaction. This strategy to generate SeBr4 in situ was used in 2015 by the same group [165], in the synthesis of selenophenothiophenes 164, through the cyclization of diheteroarylalkynes 163. The cyclization reactions were regiospecific in all cases, affording the corresponding selenophenothiophene derivatives 164a-g in modest yields (28-40%).…”

Synthesis and Characterisation of Fused Heterocyclic Molecular Rods: A Combined Experimental and Theoretical Study on Diethynyl Dithienothiophenyl Derivatives

“…These structures present the thiophene‐based homologous series of diethynyl molecular rods. Naturally, the monothiophenyl molecular rods have been extensively explored in the literature, from alkyl and silyl, groups through aromatic,,, heteroatomic aromatic substituents such as pirydyl , anisyl and methoxy, to bulky aromatic pyrene units. Due to the challenging multi‐step synthesis of the next fused‐ring homologue, thienothiophene (TT), a limited number of structures are reported and include tertiary‐butyl, trimethylsilane,, phenyl and phenylthioacetate .…”