Synthesis of fluorinated fused benzofurans and benzothiophenes: Smiles-type rearrangement and cyclisation of perfluoro(het)aryl ethers and sulfides

Design, synthesis and antitrypanosomal activities of 2,6-disubstituted-4,5,7-trifluorobenzothiophenes

“…Continuing our interest in preparing condensed sulfur containing heterocycles [17] from perfluoroarene precursors, firstly, tetrafluorobenzaldehydes 2a-e suitable for ring annelation reactions to construct the benzothiophene derivatives were prepared through the reaction of pentafluorobenzaldehyde 1 with a range of nucleophiles (Scheme 1) including two diazoles, a phenol and two thiols [18]. Treatment of the aldehydes 2 with α-mercaptocarbonyl compounds 3a or 3b was expected to lead to addition of the thiol to the 2-position of the benzaldehyde and allow condensation of the active methylene group with the adjacent aldehyde to form a fused thiophene ring 5, since thieno [2,3-c]pyridines have been prepared by a related method involving cyclisation onto a nitrile [19].…”

The Truce–Smiles rearrangement and related reactions: a review

“…58,61 Examples of Truce-Smiles rearrangements occurring through the formation of 4-membered ring spirocyclic Meisenheimer adducts are also relatively uncommon. 36,39,48,52,95 Each of the examples shown in Fig. 7 arise from isolated, seemingly adventitious, observations from a variety of research groups, making it difficult to draw conclusions from these non-systematic, inconsistent examples.…”

“…21 Similarly, there are numerous examples of successful rearrangements of 4-substituted pyridine substrates in the literature. 23,46,48,52,95 In keeping with theory, examples of the successful rearrangement of 3-substituted pyridine substrates 22,52 are the rarest for For the substrates studied by Kündig's research group, the 4-substituted pyridine substrate, 74, appears to be the superior rearrangement substrate as evidenced by a high yield of product and a brief reaction time, followed by 2-substituted pyridine substrate, 70, with the 3-substituted pyridine, 72, as the poorest substrate (Scheme 25). The comparison of these three analogous substrates is complicated by the tandem nature of the reaction, with the activating effects of the second nucleophilic aromatic substitution reaction predicted to be the opposite of the first substitution (Truce-Smiles rearrangement) in the sequence.…”

“…30,31 The studies that we have published thus far from the Wood research group have exclusively been alkyl aryl ethers. 49 Typically, an acidic aqueous work-up provides the products from these rearrangement products as the appropriate alcohol 58,61 or phenol, [44][45][46]95,96 unless the rearranged alkoxide anion intermediate has been trapped by a tandem reaction, typically cyclization to form a cyclic ethercontaining compound 49 or lactone. 94 The reaction shown in Scheme 35 represents a typical rearrangement of a diarylether, 110, formed in situ, with tandem Truce-Smiles rearrangement to yield a phenol product, 111.…”

Novel fluorinated benzimidazole-based scaffolds and their anticancer activity in vitro

“…Continuing our interest in preparing condensed polycyclic heterarenes from perfluoroarenes [24] we first explored the reaction of pentafluoropyridine 2 with 1,3-dihydro-2H-benzimidazole-2-thione 1 (Scheme 1), expecting to obtain the tetracylic-fused thiazole 3 by a tandem S N Ar addition. The thiolate group of the anion of 1 was expected to be the most nucleophilic centre and likely to attack C-4 of pentafluoropyridine first, leading to the ring fusion shown in 3, if the ring nitrogen then effected a second substitution.…”