Access to CF₃‐Containing Cyclopentaquinolinone Derivatives from Indolyl‐ynones via Silver‐Catalyzed One‐pot Reaction

Abstract

An unexpected Ag(I)-catalyzed cascade reaction between substituted indolyl-ynone and Togni's reagent has been disclosed in which multiple processes occur including indole dearomatization, ring expansion, trifluoro-methylation and dehydrogenation. This one-pot reaction can be used to conveniently access diverse CF 3 -containing multisubstituted cyclopentaquinolinone scaffolds in moderate to good yields.

A Thiol-Mediated Three-Step Ring Expansion Cascade for the Conversion of Indoles into Functionalized Quinolines

“… 3 − 6 For example, our groups and others have shown that the activation of the alkyne moiety of 1 promotes efficient dearomatizing spirocyclization 7 , 8 to form medicinally important spirocyclic indolenines 2 ; 9 , 10 this is most commonly done using π-acidic catalysts (especially Ag(I) species), although Brønsted acids, palladium(II) complexes, and electrophilic halogenation reagents can also be used ( 1 → 2 , Scheme 1 a, step 1). 3 , 11 , 12 Our groups have also shown that dearomatization works well on 2-halogenated indoles (i.e., 1 where X = Cl, Br or I) and that the resulting indoleninyl halide products (i.e., 2 where X = Cl, Br or I) can be transformed further via reaction with nucleophiles, or via Pd-catalyzed cross-coupling, to substitute the halide for various other groups ( 2 → 3 , Scheme 1 a, step 2). 5 Finally, our groups and others have demonstrated that spirocyclic indolenines of the form 3 will rearrange via a one-atom ring expansion reaction 13 to form annulated quinolines, with both acidic and basic reagents able to promote this transformation ( 3 → 4 , Scheme 1 a, step 3).…”

Synthetic and Mechanistic Studies into the Rearrangement of Spirocyclic Indolenines into Quinolines

“…The authors proposed broadly the same mechanism as that shown in Scheme b for this metal‐free variant, although again, no evidence was obtained in its support. Most recently, Song, Liu and co‐workers observed a closely related transformation unexpectedly during a silver(I)‐catalysed trifluoromethylation cascade process and the same mechanism was again proposed …”

“…To the best of our knowledge, this indolenine to quinoline rearrangement reaction is without precedent outside of these studies , , . Therefore, we believe that more convincingly ascertaining the mechanism of this unusual ring expansion rearrangement reaction is important, and our attempts to do so are reported in this manuscript using a density functional theory (DFT) approach .…”

Heteroarene‐tethered Functionalized Alkyne Metamorphosis

“…[18] Keepingthe reputation of trifluoromethyl group in attention, an easy access to CF 3 bearing heterocyclesb yt ransition metal catalystfrom indolyl ynones was reported by Li and co-workers (Scheme 7). [19] Even though metal catalyzed transformation of indolyl ynones into spiro-indoleninesa nd acid mediated transformationi nto quinolines are well explored by Unsworth group, domino trifluoromethylation was not explored.D earomatizings pirocyclization through the similarm echanism discussed earlier (Scheme 4) followed by addition of trifluoromethyl radical to the reactive intermediate 46 and successive oxidation resulted the trifluoromethylated quinoline 40 in good yield (Scheme 8). Electron donating and withdrawing substitutions on indole found to be wellt oleratedb ut aromatic substituted ynone terminus (except 4-NMe 2 -C 6 H 4 )f ound to be tolerable producing moderate to good yield.…”