Brønsted/Lewis Acid-Promoted Site-Selective Intramolecular Cycloisomerizations of Aryl-Fused 1,6-Diyn-3-ones for Diversity-Oriented Synthesis of Benzo-Fused Fluorenes and Fluorenones and Naphthyl Ketones

Abstract

Herein, a facile diversity-oriented approach to access functionalized benzo[a]fluorenes, benzo[b]fluorenones, and naphthyl ketones has been demonstrated via site-selective intramolecular cyclization of aryl-fused 1,6-diyn-3-ones. Synthesis of benzo[a]fluorenes and naphthyl ketones has been achieved selectively using TfOH and AgBF 4 , respectively, via in situ-formed acetals. Arylfused 1,6-diyn-3-ones undergo triflic acid-mediated intramolecular cyclization, leading to benzo[b]fluorenone derivatives via a radical intermediate as supported by EPR studies. Kinetic studies of these transformations have also been performed by UV−visible spectroscopic analysis to shed light on the reaction profile.

Synthesis of Highly Substituted Biaryls by the Construction of a Benzene Ring via In Situ Formed Acetals

“…We have developed a number of transformations using in situ formed acetals by reacting their parent carbonyl compounds with trimethyl orthoformate (TMOF) and a Lewis or Brønsted acid. 17 Thus, formed acetals promote certain reactions to occur that are otherwise not possible directly from the parent carbonyl compounds. Particularly, unactivated ketones in the presence of trimethyl orthoformate and a Lewis or Brønsted acid generate enol ethers, which are used as nucleophiles in the α-functionalization of unactivated ketones.…”

Regioselectivity Switch Towards the Development of Innovative Diels‐Alder Cycloaddition and Productive Applications in Organic Synthesis

“…In 2004, Carlos Saa and colleagues reported an intramolecular dehydro DA cycloaddition of diarylacetylenes where thermal cyclization of 1‐[2‐(arylethynyl)phenyl]‐3‐trimethylsilylpropynones 75 underwent rearrangement in notable switching between benzo[b]fluorenones and benzo[c]fluorenones yielded a mixture of products, including benzo[ b ]fluorenones 78 and benzo[ c ]fluorenones 79 that have immense bioactivity and necessity in organic synthesis (see Scheme 12). [122–124] The formation of benzo[b]fluorenones 78 via 80 arises from direct aromatization‐isomerization of the initial [4+2] cyclized product whereas, benzo[c]fluorenones 79 via 81 governed by six electron electrocyclic ring opening followed by aromatization‐isomerization with promising yields up to 93% as depicted in Scheme 12. The remarkable switch between benzo[b]‐ and benzo[c]fluorenones expedient during [4+2] cycloaddition pathway was one of the prominent accomplishments in the history of organic synthesis pursuits.…”

“…[120,121] In 2004, Carlos Saa and colleagues reported an intramolecular dehydro DA cycloaddition of diarylacetylenes where thermal cyclization of 1-[2- ). [122][123][124] The formation of benzo Furthermore, the distinct DA approach have been disclosed towards this end that provides an excellent example of regioselectivity based on electronic attributes of substituents and the unique role of solvents in conveniently accessing such classified biologically enriched motifs. [124] In 2019, Takanori Shibata and colleagues presented a novel use of the Diels-Alder process to manufacture dibenzoheteroles.…”

On the Shape and Synthesis of Extended Fluorenones: Recent Advances and Upcoming Challenges

“…This methodology has been demonstrated to be particularly In a recent report, Balamurugan subjected similar 1,6-diyne starting materials bearing terminal aryl groups to Brönsted acidpromoted intramolecular cycloisomerization (Scheme 33). [72] The procedure appears quite general and compatible with various substituents installed at all aromatic fragments of the reactants. As stated by the authors, TfOH is responsible for the protonation of the carbonyl group, facilitating the cyclisation into the indanone-type intermediate.…”