Facile Synthesis of Polycyclic Fluorene Derivatives via a Palladium‐Catalyzed Coupling, Propargyl‐Allenyl Isomerization and Schmittel Cyclization Sequence

Abstract

A stepwise process involving Sonogashira coupling, propargyl-allenyl isomerization and Schmittel cyclization has been realized, leading to an efficient synthesis of polycyclic fluorene derivatives from readily available starting materials. The reaction features the formation of three new carbon-carbon bonds to construct the benzene unit together with an efficient assembly of three or four rings in a single operative step.

Mechanistic Dichotomies in Coupling–Isomerization–Claisen Pericyclic Domino Reactions in Experiment and Theory

“…In particular, highly substituted indanes display biological activities such as pharmacological [20] and olfactory properties [21]. Most pleasingly, these pioneering studies on the generation of highly reactive allene intermediates by the means of the CIR has found lightning-fast application in the synthesis of polycyclic 2,3-dihydrofurans [CIR-IMDA [22] and CIRAlder-ene [23]), fluorenes (CIR-Schmittel cyclization) [24] and pyrroles (CIR-(3 þ 2)] [25].…”

Synthesis of Carbo- and Heterocycles via Coupling-Isomerization Reactions

“…1-(2-Alkynylphenyl)propargyl ethers 66 are rigidified propargyl substrates that also participate in CIR-cycliza-tion domino sequences, giving rise to the formation of polycyclic fluorene derivatives 67 in moderate to excellent yields (Scheme 27). 56 Mechanistically, it is still debatable whether the cyclization occurs via a Schmittel radical cyclization, 57 as suggested by the authors, or via the [4+2]-aromatization pathway.…”

Palladium-Catalyzed Q-Tube-Assisted Protocol for Synthesizing Diaza-dibenzo[a,e]azulene and Diaza-benzo[a]fluorene Derivatives via O2 Acid-Promoted Cross-Dehydrogenative Coupling

“…Among these fused nitrogen-heteroaromatics are aza-benzoazulene and aza-benzofluorene derivatives and their analogy, which have a variety of medicinal and pharmacological activities such as anti-inflammatory, − anticancer, − antitumor, − antidiabetic, antimicrobial, and antimycobacterial . Also they can serve as dopamine D4 receptor ligands to treat erectile dysfunction , and as a dopamine D3 agonist for the treatment of several neurological disorders such as anxiety, major depression, and schizophrenia. , In addition, members of this class of compounds have been used as building blocks in materials developed with distinctive optical and electrical characteristics. − Therefore, it may be inferred that the azulene- and fluorene-based compounds are patentable and are regarded as essential motifs in drug development, even though they have not been extensively employed until now. But the synthetic routes to access these compounds based on azulene and fluorene are limited and not widely explored. − As a result, novel synthetic routes toward polysubstituted aza-azulene- and aza-fluorene-based compounds need to be developed.…”