Efficient Synthesis of Fluoren-9-ones by the Palladium-Catalyzed Annulation of Arynes by 2-Haloarenecarboxaldehydes

Abstract

Fluoren-9-ones and derivatives are readily prepared in good yields by the annulation of in situ generated arynes by 2-haloarenecarboxaldehydes in the presence of a palladium catalyst.

Iodine-mediated synthesis of benzo[a]fluorenones from yne-enones

“…2 Despite their importance in the elds of medicine and materials science, only a handful of methods are available to access benzo[a]uorene derivatives, especially for benzo [a]uorenones. 3 The recent methods available for the synthesis of benzo[a]uorenones include thermal cyclization of diaryldiynones, 4 Suzuki coupling of functionalized arenes followed by cyclization, 5 annulation of arynes with 2-haloarenecarboxaldehydes, 6 and gold-catalyzed cyclization of trityl-substituted diynes followed by oxidative photocyclization. 7 While exploring the synthetic potentials of o-alkynylchalcones, 8 we discovered that related yne-enones 1 when heated under reux with iodine in AcOH gave benzo[a]uorenones 2 through a cascade process (Scheme 1, eqn (1)).…”

Facile and Diverse Synthesis of Benzo[b]fluorenone Derivatives through a Copper/Selectfluor‐Catalyzed Tandem Annulation of 1,6‐Enynes

“…Regarding synthetic strategy, the classical methods for the construction of fluorenones (benzo[ b ]fluorenones) include Friedel–Crafts ring closures of biarylcarboxylic acids and their derivatives, oxidation of fluorenes, and intramolecular [4+2] cycloaddition reactions of diarylacetylenes or conjugated enynes . Thanks to the high efficiency of palladium catalysts in the formation of C–C bonds, several methods for the construction of fluorenones (benzo[ b ]fluorenones) involving palladium‐catalyzed annulations have been developed in recent decades . These include [2+2+2] cycloaddition reactions of benzyne, cyclocarbonylation of o ‐halobiaryls, annulation of 2‐haloarenecarboxaldehydes with arynes or arylboronic acids, intramolecular arylation of o ‐halobenzophenones,[4a] dual C–H functionalization of benzophenones, and directing‐group‐assisted dual C–H activations .…”

“…Thanks to the high efficiency of palladium catalysts in the formation of C–C bonds, several methods for the construction of fluorenones (benzo[ b ]fluorenones) involving palladium‐catalyzed annulations have been developed in recent decades . These include [2+2+2] cycloaddition reactions of benzyne, cyclocarbonylation of o ‐halobiaryls, annulation of 2‐haloarenecarboxaldehydes with arynes or arylboronic acids, intramolecular arylation of o ‐halobenzophenones,[4a] dual C–H functionalization of benzophenones, and directing‐group‐assisted dual C–H activations . Recently, some other methods have also been reported, including DDQ (2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone)‐mediated oxidative radical cycloisomerization of 1,5‐diynols, aluminum‐oxide‐mediated C–F bond activation of trifluoromethylated arenes, and quaternary‐ammonium‐salt‐promoted intramolecular dehydrogenative arylation of aldehydes .…”

An Effective Synthesis Method for Tilorone Dihydrochloride with Obvious IFN-α Inducing Activity

“…Moreover, it has been gradually proved to possess extensive pharmacological functions, such as enhanced phagocytic activity of natural killer cells [3], anti-pyretic [4], anti-fibrotic [5], anti-inflammatory [6,7,8,9,10], anti-virus [11,12], anti-tumor [13,14,15], as well as interferon induction [16,17,18]. All the effects are attributed to its planar structure of a modification of the fluorenone skeleton and amino side chain [15,19,20,21]. The skeleton comes straight from 2,7-dihydroxyfluoren-9-one ( 2 , Figure 1), which can be substituted by appropriate dialkylaminoalkyl halides to give tilorone and other compounds [15].…”