Synthesis of Polycyclic Furan and Chromene Derivatives via Cascade Reactions Enabled by Cleavage of Multiple C(sp³)−F Bonds

Abstract

The strong and unreactive CÀ F bond makes polyfluorocarbons extremely long-lived and potentially toxic. A successive selective and controllable C(sp 3)À F functionalization of polyfluoroalkylated ketones with Sand O-nucleophiles to enable efficient synthesis of pharmaceutically important fluorine-and sulfurcontaining polycyclic furan and chromene derivatives under transition metal-free conditions is demonstrated here. The combination of CÀ S/CÀ O coupling, aromatization, and cyclization cascade contribute to the accurate four/five C(sp 3)À F bond cleavage at two different sites of perfluoroalkyl chain. The formation of reactive quinoid intermediates and the necessity of using TBAB (tetrabutylammonium bromide) as additive and Cs 2 CO 3 as base were identified by detailed mechanistic studies.

Three-Component Bisannulation for the Synthesis of Trifluoromethylated Tetracyclic Aza-Aromatics through Six C(sp3)–F Bond Cleavage and Four C–N Bond Formation

“…On the basis of these obtained results, a proposed mechanism is outlined in Scheme . − Initially, a successive defluorination of perfluoroalkyl substrate 1 under the effect of the alkali-metal base gives unstable naphthalen-1­(4 H )-one intermediate B , which further undergoes the condensation with benzamidine 2 to afford the imine species C . The following intramolecular defluorinative amination of resultant intermediate C through 7- endo-trig cyclization furnishes the ring-closure product E .…”

“…The existence of TBAB might contribute to autoaromatization. It is possible that the TBAB additive would accelerate both events of intermolecular condensation reaction and intramolecular C–N formations, but the detailed mode of this action remained elusive. , …”

“…Selective trifluoromethylation of a specified C–H bond in (hetero)­arenes remains a fundamental challenge. Recently, our laboratory has leveraged the distinctive fluorine effect for heteroannulation, where the synthetic linchpin for realizing the assembly of fluoro-organic molecules is controlled by successive selective defluorination at different centers. − Reactive quinoid species are key intermediates for the C–F bond functionalization and heterocycle construction. Although the reactions of perfluoroalkyl ketones with amidines to form pyrimidine derivatives have been well studied, the accurate six C­(sp 3 )–F bond cleavage at three different sites by using these quinoid species has never been reported until now .…”

Three‐Component Synthesis of 2‐Substituted Thiobenzoazoles Using Tetramethyl Thiuram Monosulfide (TMTM) as Thiocarbonyl Surrogate

“…However, the control experiments without any catalyst (entry 14) showed that catalyst was not crucial in this reaction. To our delight, the reaction would be significantly promoted when a series of bases were added (entries [15][16][17][18][19][20][21][22][23], and the screening of bases showed that Na 2 CO 3 was the best. Thus, the optimal reaction conditions were summarized in entry 15, Table 1.…”

“…In recent years, owing to the pursuit of economy and ecofriendliness, alkali-catalyzed reactions, especially alkali metal carbonates, have become more and more popular. [16] Shen and co-workers [17] developed a highly selective functionalized C(sp 3 )-F bond formation strategy by efficient combination of TBAB (tetra-n-butylammonium bromide) and Cs 2 CO 3 . Shi [18] disclosed the cascade dimerization and cyclization of 2-sulfoaminoacrylate derivatives catalyzed by the inorganic base K 2 CO 3 to synthesize dihydro-2-oxopyrrole (DPO) derivatives in one step.…”