Sigmatropic Dearomatization/Defluorination Strategy for C−F Transformation: Synthesis of Fluorinated Benzofurans from Polyfluorophenols

Abstract

Facile synthesis of fluorinated benzofurans from polyfluorophenols has been accomplished by means of a sigmatropic dearomatization/defluorination strategy composed of three processes: (1) interrupted Pummerer reaction of ketene dithioacetal monoxides with polyfluorophenols followed by [3,3] sigmatropic rearrangement, (2) Zn-mediated smooth reductive removal of fluoride from the dearomatized intermediate, and (3) acid-promoted cyclization/aromatization. Mechanistic investigations revealed important characteristic reactivity of polyfluorophenols in the present system. Some of the fluorinated benzofuran products were transformed by utilizing the 2-methylsulfanyl moieties.

C−F Arylation of Polyfluorophenols by Means of Sigmatropic Dearomatization/Defluorination Sequence

“…Recently,w eh ave demonstrated as igmatropic dearomatization/defluorination sequence as an ew strategy for selective CÀFt ransformations of polyfluorophenols for annulative synthesiso ff luorinated benzofurans (Scheme 1a). [9,10] In the presence of trifluoroacetica nhydride (TFAA), polyfluorophenols undergoi nterrupted Pummererr eaction [11] with ketene dithioacetal monoxide (KDM) to form SÀO-tethered sulfonium A.T hen, CÀCb ond-forming charge-accelerated [3,3] sigmatropic rearrangemento ccurs with dearomatization of the phenol ring to give dearomatized intermediate B. [12] Subsequent addition of Zn induces reductive defluorination to form phenol C.A ssisted by rearomatization, the reductive defluorinationp roceeds with the moderate reducing agent underm ild reaction conditions.…”

“…With benzothienyls ulfoxide 1a and 2,6-difluorophenol (2a) as models ubstrates, we optimized the reactionc onditions based on our previous defluorinative transformation. [9] Optimization study revealed that TFAA (2.0equiv) and Zn powder (5.0 equiv) were found to be optimal as an activatora nd as a reductant,r espectively. [13] Moreover,a na ddition of as mall amount of trifluoroacetic acid (TFA) wasc rucial for the reproducibility of the reaction.…”

“…This non-regioselective sigmatropic rearrangement is consistent with our previousr eport on the reactiono fK DM with 2-fluorophenol. [9] The lack of the regioselectivity highlights the necessity of 2,6-difluorophenol (2a)f or the selective synthesis of fluorinated biaryl 3aa.…”

Last Decade of Unconventional Methodologies for the Synthesis of Substituted Benzofurans

“…In 2018, they accomplished a facile synthesis of fluorinated benzofurans from polyfluorophenols by means of a sigmatropic dearomatization/defluorination strategy composed of three processes: (1) interrupted Pummerer reaction of ketene dithioacetal monoxides, activated by TFFA, with polyfluorophenols followed by [3,3] sigmatropic rearrangement; (2) Zn-mediated smooth reductive removal of fluoride from the dearomatized intermediate; and (3) acid-promoted cyclization/aromatization to lead to benzofuran in 90% overall yield. Some of the fluorinated benzofurans were transformed by utilizing the 2-methylsulfanyl moieties [179] (Scheme 54). Procter's group reported a transition-metal-free synthesis of benzofurans from benzothiophenes and phenols which exploited the unique reactivity of sulfoxides [180].…”

“…(1) interrupted Pummerer reaction of ketene dithioacetal monoxides, activated by TFFA, with polyfluorophenols followed by [3,3] sigmatropic rearrangement; (2) Zn-mediated smooth reductive removal of fluoride from the dearomatized intermediate; and (3) acid-promoted cyclization/aromatization to lead to benzofuran in 90% overall yield. Some of the fluorinated benzofurans were transformed by utilizing the 2-methylsulfanyl moieties [179] (Scheme 54). Palladium-catalyzed oxidative annulations between phenols and alkenylcarboxylic acids produced a library of benzofuran compounds.…”